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FIBRINOLYTICS &
ANTIFIBRINOLYTICSBy Dr.Elza Emmannual
FIBRINOLYTICS
Drugs used to lyse thrombi to recanalize occluded blood vessels
Works by activating the natural fibrinolytic system
NATURAL FIBRINOLYTIC SYSTEM
PLASMINOGEN
FIBRIN FRAGMENTS
FIBRIN
PLASMIN
ACTIVATORSt-PA, Kallikrein,Factor Xa
INHIBITORSα2 Antiplasmin
α2 Macroglobulin
• Venous thrombi lysed more easily
• Recent thrombi respond better
• Little effect on thrombi >3 days old
Clinically important fibrinolytics are,
• Streptokinase
• Urokinase
• Alteplase (rt PA)
• Reteplase
• Tenecteplase
Streptokinase• Source:β haemolytic streptococci group C
• Inactive as such
• Combines with circulating plasminogen forms activator complex proteolysis of plasminogen Active plasmin
• Cheap,widely used in India
Disadvantages1.Activates both circulating & fibrin bound plasminogenDepletion of circulating plasminogen → bleeding
2. Antistreptococcal Abs from past infections inactivate considerable fraction of initial dose , loading dose needed
3.AntigenicHSR & anaphylaxis when used for 2nd time
4.Repeat doses less effective due to neutralisation by Abs
Urokinase• Isolated from human urine ,now from cultured human
kidney cells
• Activates plasminogen directly
• Moderately specific to fibrin bound plasminogen
• Nonantigenic
• Indicated in whom streptokinase has been used for an earlier episode
Alteplase Produced by recombinant DNA technology
•Nonantigenic
•Short t1/2 so given as slow IV infusion
•ExpensiveReteplase Produced by
recombinant DNA technology
•Modified form of rt-PA
•Long acting
•So given as bolus dose repeated in 30 min
Tenecteplase
Produced by r DNA technology
•Mutant variant of rt-PA•Long duration of action•Single IV bolus
USES1.Acute MI –
– chief indication,alternate to emergency percutaneous coronary intervention with stent placement
– Golden period-1hr,Better results- within 3hrs
– Timelag in starting infusion is critical in • Reducing area of necrosis• Preserving ventricular function• Reducing mortality
2.Deep vein thrombosis
3.Pulmonary embolism
4.Peripheral arterial occlusion
5.Stroke- – rt-PA –approved for treatment of ischaemic stroke– treated within 3 hours of onset– intracranial hemorrhage has to be ruled out
CONTRAINDICATIONS• All situations where the risk of bleeding is increased– Recent trauma– Surgery– Biopsy– Hemorrhagic stroke– Peptic ulcer– Severe hypertension– Aneurysms– Bleeding disorders– Diabetes– Acute pancreatitis– pregnancy
ANTIFIBRINOLYTICS
Drugs which inhibit plasminogen activation & dissolution of clot
EPSILON AMINO-CAPROIC ACID(EACA)
• Analogue of lysine
• Binds to lysine binding sites of plasminogen & plasmin so that it cannot bind to fibrin & lyse the clot
USES
• Overdose of fibrinolytics
• To prevent recurrence of G.I & subarachnoid hemorrhage
• Certain traumatic & surgical bleedings like prostatectomy,tooth extraction in haemophiliacs
• Abruptio placentae,PPH & menorrhagia
Adverse Effects• In hematuria –ureteric obstruction by the unlysed clots
• Intravascular thrombosis
• Hypotension,bradycardia,arrhythmias
• Caution in impaired renal function
• Myopathy
TRANEXAMIC ACID• MOA-similar to EACA• 7 times potent than EACA• Preferred drug for bleeding due to– Fibrinolytic drugs– Cardiopulmonary bypass surgery– Tonsillectomy,prostatic surgery,tooth extraction in
haemophiliacs– Menorrhagia– Recurrent epistaxis,hyphema due to ocular
trauma,peptic ulcer
Adverse Effects
• Nausea• Diarrhoea• Thromboembolic events• Disturbed colour vision• Allergic reactions• Thrombophlebitis
PLASMINOGEN
FIBRIN FRAGMENTS
FIBRIN
PLASMIN
ACTIVATORS
INHIBITOR
• Streptokinase• Urokinase• Alteplase• Reteplase• Tenecteplase
• EACA• Tranexaemic acid
THANK YOU