Upload
sam-levine
View
128
Download
7
Embed Size (px)
Citation preview
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
A. Q. Sangalang, MD, FPOGS, RMTFACULTY OF PHARMACY
UNIVERSITY OF SANTO TOMAS
DRUGS USED INCOAGULATION
DISORDERS
MECHANISM OF BLOOD COAGULATION
Vascular endothelial cell layer lining blood vessels
• Anticoagulant phenotype
• Blood platelets and clotting factors do not normally adhere to it
In cases of vascular injury
• It undergoes change to a more procoagulant phenotype
● Platelet adherence and activation
● Secretion and synthesis of vasoconstrictors and platelet activating molecules
DRUGS USED IN COAGULATION AND BLEEDINGDISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Thromboxane
• Synthesized from arachidonic acid within platelets
• Platelet activator and potent vasoconstrictor
Adenosine diphosphate (ADP)
• Product secreted from platelet granules
• Powerful inducer of platelet aggregation
DRUGS USED IN COAGULATION ANDBLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Serotonin (5 HT)
• Product secreted from platelet granules
• Stimulates aggregation and vasoconstriction
Glycoprotein IIb/IIIa
• Receptor changes its conformation upon activation of platelets enabling it tobind fibrinogen
• Cross-links adjacent platelets resulting in aggregation and platelet plugformation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
MECHANISM OF BLOOD COAGULATION
Coagulation system is then activated resulting in thrombin generation andfibrin clot formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Tissue factor (TF)
• Main initiator of blood coagulation in vivo
• Expressed outside the blood vessel but not normally expressed in an activeform within the vessel
• Damaged endothelium allows binding of TF to factor VIIa (proconvertin)forming a complex
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
BLOOD COAGULATIONCASCADE
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
MECHANISM OF BLOOD COAGULATION
Fibrinolysis
• Process of fibrin digestion by the fibrin-specific protease, plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
Loading...
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Drugs used in patients at risk for vascular occlusion to decrease clotting ordissolve clots already present
• Drugs used to increase clotting in patients with clotting deficiencies
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticlotting drugs
●Myocardial infarction and other acute coronary syndromes
● Atrial fibrillation
● Ischemic stroke
● Deep vein thrombosis (DVT)
● Effective in treatment of both venous and arterial thrombosis
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Primary Groups of Drugs used in Clotting and Bleeding Disorders
• Anticoagulants and thrombolytic drugs
● Effective in treatment of both venous and arterial thrombosis
• Antiplatelet drugs
● Used for the treatment of arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Classification
• 3 major types of anticoagulants
● Indirect thrombin inhibitors
● Heparin and related product
● Given IV
● Direct thrombin inhibitors
● Given IV
● Coumarin derivatives
●Warfarin
● Orally active
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Large sulfated mucopolysaccharide polymer
• Obtained from animal sources
• Contains molecules of varying size
● Average molecular weight of 5,000-30,000 per batch
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Unfractionated Heparin (UFH) High Molecular-Weight Heparin (HMWH)
• Highly acidic
• Neutralized by basic molecules (e.g., protamine)
• Given parenterally
● IV or subcutaneously
• Intramuscular injection is avoided
● Risk of hematoma formation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Low-Molecular-Weight Heparin (LMWH)
• Enoxaparin, dalteparin, tinzaparin
• Have molecular weights of 2000-6000
• Have equal efficacy, greater bioavailability and longer durations of actionthan regular heparin
• Can be given less frequently (once or twice a day)
• Given subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Fondaparinux
• Small synthetic drug
• Contains the key pentasaccharide present in unfractionated and LMW heparins
• Administered subcutaneously once daily
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Chemistry
Danaparoid
• LMW heparinoid containing heparan, dermatan and chondroitin sulfates
• Chemically distinct from heparin (no cross-hypersensitivity)
• Can be given intravenously or subcutaneously
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Binds to endogenous antitrhrombin II (ATIII) via a key saccharide sequence
• ATIII
● Inhibits clotting factor proteases especially thrombin (IIa), Ixa and Xa
● In the absence of heparin, these reactions are slow
● In the presence of heparin, they are accelerated 1000-fold
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
Unfractionated heparin
• Provides anticoagulation immediately after administration
• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Bind to ATIII
• Same inhibitory effect on factor Xa as the regular heparin-ATIII complex
• More selective action because they fail to affect thrombin (IIa)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Mechanism and effects
LMW heparins and fondaparinux
• Weight-based dosing results in predictable pharmacokinetics and plasmalevels
• Levels are not measured except in renal insufficiency, obesity and pregnancy
• aPTT test does not reliably measure the anticoagulant effect of the LMWheparins and fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Used when anticoagulation is need immediately (e.g., when starting therapy)
• Common uses
● DVT
● Pulmonary embolism
● Acute myocardial infarction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Combined with thrombolytics for revascularization
• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Clinical use
Heparin
• Does not cross the placental barrier
● Drug of choice in pregnancy
• LMW heparins and fondaparinux
● Similar clinical applications
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Increased bleeding
• Most common adverse effect
• May result in hemorrhagic stroke
Protamine sulfate
● Highly basic peptide that combines with heparin
● Forms a stable complex devoid of anticoagulant activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Protamine sulfate
● 1 mg given IV/10 units of heparin left in the patient
● Not to exceed 50 mg in any 10 minute period
● Only partially reverses the effects of LMW heparins
● Does not affect the action of fondaparinux
● Excess danaparoid is removed by plasmapheresis
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
Heparin-Induced Thrombocytopenia (HIT)
● Occurs in 1-4% of patients treated for a minimum of 7 days
● Hypercoagulable state
● Produce an antibody that binds to a complex of heparin and platelet factor
● Treated by discontinuance of heparin and administration of a directthrombin inhibitor or fondaparinux
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Indirect thrombin inhibitors
• Toxicity
• LMW heparins, fondaparinux and danaparoid
● Less likely to cause this immune-mediatedthrombocytopenia
• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
• Bind directly to the active site of thrombin inhibiting its downstream effect
• Derived from proteins made by Hirudo medicinalis, the medicinal leech
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Hirudin
• Specific irreversible thrombin inhibitor from leech saliva
• Given IV
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Lepirudin
• Recombinant form of the leech protein hirudin
• Given IV
• Excreted by the kidneys
● Can accumulate in patients with renal failure
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Bivalirudin
• Modified form of hirudin
• Given IV
• Rapid onset and offset of action
• Clearance is 20% renal and the remainder is
metabolic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Chemistry and pharmacokinetics
Argatroban
• Small molecule
• Clearance not affected by renal disease
• Dependent on liver function
● Can accumulate in patients with liver disease
• Administered parenterally
• Monitored by aPTT
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
Lepirudin and bivalirudin
• Bind simultaneously to the active site of thrombin and to thrombin substrates
Bivalirudin
• Also inhibits platelet activation
Argatroban
• Binds solely to thrombin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Mechanism and effects
• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Clinical use
• 3 drugs monitored using aPTT lab test
Lepirudin and argatroban
• Alternatives to heparin in patients with HIT
Bivalirudin
• Used in combination with aspirin during percutaneous transluminal coronaryangioplasty
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Parenteral Direct Thrombin Inhibitors
• Toxicity
• Can cause bleeding
• No reversal agents exist
• Prolonged infusion of lepirudin
● Induce formation of antibodies that form a complex and prolong itsaction
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Advantages
• Predictable pharmacokinetics and bioavailability
● Fixed dosing
● Predictable anticoagulant response
• Routine coagulation monitoring is unnecessary
• Do not interact with CP450-interacting drugs
• Rapid onset of action
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Direct Thrombin Inhibitors
Oral Direct Thrombin Inhibitors
Ximelagatran
• First oral drug approved
• Withdrawn due to hepatic toxicity
Dabigatran
• Equivalent efficacy and safety to LMWH
• Prevention of venous thromboembolism in patients who underwent hip orknee replacement surgery
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Small, lipid-soluble molecules that are readily absorbed after oraladministration
• Cross the placenta
● Potentially dangerous to the fetus
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• One of the most commonly prescribed drugs
• Administered as a sodium salt with 100% bioavailability
• Highly bound to plasma proteins (>99%)
• Half-life of 36h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Chemistry and pharmacokinetics
Warfarin
• Racemic mixture
● S-warfarin is 4x more potent than the R-warfarin
• Elimination depends on metabolism by CP450 enzymes
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Interfere with the normal posttranslational modification of clotting factors inthe liver
● Process that depends on vitamin K
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X
• Results in incomplete coagulationmolecules that are biologically inactive
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Half-lives of 8-60 h
● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Warfarin and other coumarins
• Monitored by the prothrombin time (PT or “pro-time”) test
● Should be increased to a level representing reduction of prothrombin
activity to 25% of normal
● Therapeutic range is defined in terms of international normalized ratio(INR)
● Prothrombin time ratio
● Patient prothrombin time/mean of normal prothrombin time for lab
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Vitamin K-dependent factors
• VII
• IX Half-lives of 6, 24, 40,and 60 h in plasma
• X respectively
• II
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Stop the drug
• Administer oral or parenteral vitamin K1
● Phytonadione
• Recovery is slow
● Requires the synthesis of new normal clotting factors
● 6-24 h
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains
● Normal clotting factors
● Prothrombin complex concentrates
● Recombinant factor VIIa
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Mechanism and effects
Reversal of the action of warfarin
• Disappearance of excessive effect
● Not correlated with warfarin concentration
● Reestablishment of normal clotting activity
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Clinical use
• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin
• Contraindicated in pregnant women
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
Bleeding
• Most important adverse effect of warfarin
Early in therapy
• Hypercoagulability with subsequent dermal vascular necrosis can occur
● Due to deficiency in protein C
● Endogenous vitamin K dependent anticoagulant
● Very short half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Toxicity
• Can cross the placenta
● Hemorrhage in the developing fetus
● Abnormal bone formation
• Has a narrow therapeutic window
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450-inducing drugs
Increase warfarin’s clearance
Reduce the anticoagulant effect of a given dose
Barbiturates, carbamazepine, phenytoin, rifampin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTICOAGULANTS
• Coumarin anticoagulants
• Drug interactions
• Cytochrome P450 inhibitors
Reduce warfarin’s clearance
Increase the anticoagulant effect of a given dose
Amiodarone, SSRI, cimetidine
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
PROPERTIES OF HEPARINS AND WARFARINS
Property Heparins Warfarin
Structure Large polymers, acidic Small lipid-soluble molecule
Route of administration Parenteral Oral
Site of action Blood Liver
Onset of action Rapid (seconds)Slow, limited by half-lives of factors beingreplaced
Mechanism of actionActivates antithrombin III, whichproteolyses factors including thrombin andfactor Xa
Impairs post translational modification offactors II, VII, IX, X
MonitoringaPTT for unfractionated heparin but notLMW heparins
PT
AntidoteProtamine for unfractionated heparin butnot LMW heparins
Vitamin K, plasma
Use Mostly acute, over days Chronic, over weeks to months
Use in pregnancy Yes No
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Platelet aggregation
• Plays a central role in the clotting process
• Important in clots that form in the arterial circulation
• Facilitated by thromboxane, ADP, fibrin, serotonin and other substances
• Agents that increase intracellular cyclic adenosine monophosphate (cAMP)
● Prostacyclin
● Inhibit platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
COX inhibitors
• Aspirin and other NSAIDs
Inhibitors of phosphodiesterase 3
• Dipyridamole and cilostazol
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
Antagonists of ADP receptors
• Ticlopidine and clopidogrel
Glycoprotein IIb/IIIa receptor inhibitors
• Abciximab, tirofiban, eptifibatide
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Classification and prototypes
• Increase bleeding time
● Test used to monitor their effects
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin and other NSAIDs
• Inhibit thromboxane synthesis by blocking the enzyme cyclooxygenase
Thromboxane A2
• Potent stimulator for platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
• Potent stimulator for platelet aggregation
ANTIPLATELET DRUGS
A. Mechanism of action
Aspirin
• Irreversible enzyme inhibitor
• Particularly effective
• Inhibition persists until new platelets areformed (several days)
• Other NSAIDs cause less persistentantiplatelet effect (hours)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Ticlopidine and clopidogrel
• Irreversible inhibition of the ADP receptor
• Inhibition of ADP-mediated plateletaggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Abciximab
• Monoclonal antibody
• Reversibly inhibits the binding of fibrinand other ligands to the plateletglycoprotein IIb/IIIIa
● Glycoprotein IIb/IIIIa
● Cell surface protein that is involvedin platelet cross-linking (“finalcommon pathway”)
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Tirofiban and eptifibatide
• Reversibly block the glycoprotein IIb/IIIa receptors
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Mechanism of action
Dipyridamole and cilostazol
• Dual mechanism of action
● Prolong platelet-inhibiting action of intracellular cAMP inhibitingphosphodiesterase 3
● Phosphodiesterase 3
● Enzyme that degrades cAMP
● Prevent the uptake of extracellular adenosine
● Acts through platelet adenosine A2 receptors to increase platelet cAMP
● Inhibits platelet aggregation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Aspirin
• Prevents further infarcts in individuals who had one or more myocardialinfarcts
• May reduce the incidence of first infarcts
• Used extensively to prevent transient ischemic attacks (TIA), ischemicstroke, and other thrombotic events
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Clopidogrel and Ticlopidine
• Effective in preventing TIAs and ischemic strokes, especially in patients whocannot tolerate aspirin
• Prevent thrombosis in patients who have recently received a coronary arterystent
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Clinical use
Glycoprotein IIb/IIIa inhibitors
• Prevent restenosis after coronary angioplasty
• Used in acute coronary syndromes
● Unstable angina, and non-Q wave acute myocardial infarction
Dipyridamole and cilostazol
● Used to treat intermittent claudication
●Manifestation of peripheral arterial disease
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
A. Toxicity
Aspirin and other NSAIDs
• Cause GI and CNS effects
All antiplatelet drugs
• Significantly enhance the effects of other anticlotting agents
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
Ticlopidine
• Bleeding in up to 5% of patients
• Severe neutropenia in about 1%
• Rare thrombotic thrombocytopenic purpura (TTP)
Clopidogrel
• Less hematoxic
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
ANTIPLATELET DRUGS
• Toxicity
Glycoprotein IIb/IIIa receptor blocking drugs
• Bleeding
• Thrombocytopenia (with chronic use)
Dipyridamole and cilostazol
• Headaches
• Palpitations
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Classification and Prototypes
Tissue plasminogen activator (t-PA)
• Alteplase, tenecteplase, and reteplase
Anistreplase
Urokinase
Streptokinase
• All are given IV
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
Plasmin
• Normal endogenous fibrinolytic enzyme
• Promotes the breakdown and dissolution of clots
• Thrombolytic enzymes
● Catalyze the activation of the inactive precursor, plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
• t-PA
• Large human protein
• Directly converts fibrin-bound plasminogen to plasmin
• Selectivity is quite limited
• Less danger of spontaneous bleeding
Alteplase
• Normal human plasminogen activator
Tenecteplase
• Mutated form of t-PA with a longer half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Tissue plasminogen activator
Reteplase
• Mutated form of human t-PA with similar effects
• Slightly faster onset of action and longer duration of action
• Urokinase
• Extracted from cultured human kidney cells
• Directly converts plasminogen to plasmin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Streptokinase
• Obtained from bacterial cultures
• Not an enzyme
• Forms a complex with endogenousplasminogen
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Mechanism of action
• Anistreplase
• Anisoylated plasminogen-streptokinase activator complex (APSAC)
• Prodrug
• Anisoyl group is hydrolyzed in vivo
● Slow spontaneous process
• Streptokinase-activated plasminogen is released and converts plasminogen toplasmin
● Long half-life
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
Loading...
PROPERTIES OF THROMBOLYTIC AGENTS
Agent Source Duration of Action Comments
Alteplase, reteplase,tenecteplase
Recombinant human proteins 2 – 10 min
Active tissue plasminogenactivator (t-PA); convertsplasminogen to plasmin;
intravenous infusion (alteplase)or bolus doses (reteplase,
tenecteplase). Most expensive.Reteplase and tenecteplase arelonger acting than alteplase.
AnistreplaseProdrug: streptokinase plus
recombinant humanplasminogen
1 – 2 h
Slowly relases streptokinase-activated plasminogen; singlebolus administration provides
long duration of action
Streptokinase Bacterial product 20 – 25 min
Streptokinase combined withplasminogen; the combination
converts plasminogen toplasmin; intravenous infusion
required. Least expensive
Urokinase Human cell kidney culture <20 min Active plasminogen activator
DRUGS USED IN COAGULATION AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Clinical use
• Emergency treatment of coronary artery thrombosis
● Under ideal conditions (within 6 h)
● Prompt recanalization of the occluded vessel
● Very prompt use (within 3 h of the first symptoms) in patients withischemic stroke
● Significantly better clinical outcome
● Used in cases of multiple pulmonary emboli
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN COAGULATION
AND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Bleeding
• Most important hazard
• Same frequency with all drugs
Cerebral hemorrhage
• Most serious manifestation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
THROMBOLYTIC AGENTS
• Toxicity
Urokinase, t-PA, variants of t-PA
• Human proteins
• Do not evoke the production of antibodies
• Together with anistreplase
● Much more expensive
● Not much more effective
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Inadequate blood clotting
• May result from
● Vitamin K deficiency
● Genetically determined errors of clotting factor synthesis
● Hemophilia
● Variety of drug-induced conditions
● Thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
Treatment
• Vitamin K
• Preformed clotting factors
• Antiplasmin drug
• Platelets for thrombocytopenia
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Fat-soluble vitamin
• Dietary requirement is low
● Additionally synthesized by bacteria that colonize the human intestine
• Two natural forms
● Vitamin K1 (phytonadione), found in food
● Vitamin K2 (menaquinone), synthesized by intestinal bacteria
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Vitamin K
• Deficiency of vitamin K
● Common in newborns and in older individuals with abnormalities of fatabsorption
● Treated with oral or parenteral vitamin K supplements
● Phytonadione (K1)
• Large doses are used to reverse the anticoagulant effect of excess warfarin
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Clotting Factors
• Most important agents used to treat hemophilia
● Fresh plasma
● Purified human blood clotting factors, especially factor VIII and FactorIX
● Purified from blood products or produced by recombinant DNAtechnology
● Extremely expensive
● Carry a risk of infection (because of contamination by blood-bornepathogens for factors purified from blood products) and immunologicreactions
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
• Management of acute bleeding episodes in hemophiliacs and others withbleeding disorders
Aminocaproic acid and tranexamic acid
• Orally active
• Inhibit fibrinolysis by inhibiting plasminogen activation
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS
DRUGS USED IN BLEEDING DISORDERS
• Antiplasmin Agents
Aprotinin
• Serin protease inhibitor (serpin)
• Inhibits fibrinolysis by free plasmin
• Associated with increased risk of renal failure, heart attack and stroke
DRUGS USED IN COAGULATIONAND BLEEDING DISORDERS