DRUGS AFFECTING BLOODDRUGS AFFECTING BLOOD

COAGULATIONCOAGULATION

Lector prof. Posokhova K.A.Lector prof. Posokhova K.A.

Clinical ThrombosisClinical Thrombosis

> 2.5 million cases of deep venous > 2.5 million cases of deep venous thrombosis (DVT) per yearthrombosis (DVT) per year

> 600,000 cases of pulmonary > 600,000 cases of pulmonary embolism (PE) per yearembolism (PE) per year

> 50,000 deaths per year from PE> 50,000 deaths per year from PE > 11,000 post surgical PE deaths per > 11,000 post surgical PE deaths per

yearyear

ANTITHROMBOTIC THERAPYANTITHROMBOTIC THERAPY

1) Antiplatelet therapy1) Antiplatelet therapy

2) Anticoagulant therapy2) Anticoagulant therapy

3) Thrombolytic therapy3) Thrombolytic therapy

INHIBITORS OF PLATELET INHIBITORS OF PLATELET AGGREGATIONAGGREGATION

Anti Platelet DrugsAnti Platelet DrugsDrugDrug MechanismMechanism UsesUses

AspirinAspirin Permanently Permanently inhibits COX-1 inhibits COX-1 and COX-2and COX-2

CADCAD

Stroke-TIAsStroke-TIAs

NSAIDsNSAIDs Reversibly Reversibly inhibits COX-1inhibits COX-1

LimitedLimited

DipyridamoleDipyridamole Inhibits PDE; Inhibits PDE; increases cAMPincreases cAMP

TIAsTIAs

TiclopidineTiclopidine

ClopidogrelClopidogrel

Inhibits ADP Inhibits ADP PlatAg; active PlatAg; active metabolitemetabolite

TIAs; StrokeTIAs; Stroke

CAD; PVDCAD; PVD

Platelets inhibitors - ASAPlatelets inhibitors - ASA

Daily dose -Daily dose - 80-300 80-300 mgmg

KardiomagnilKardiomagnil

ANTIPLATELET THERAPYANTIPLATELET THERAPY

Aspirin IndicationsAspirin Indications

1)1) Stroke, TIA (transient ischemic Stroke, TIA (transient ischemic attacks)attacks)

2)2) MI, recurrent MIMI, recurrent MI3)3) Unstable anginaUnstable angina

4)4) CABG potency (CABG potency (coronary coronary artery bypass graftartery bypass graft ))

TICLOPIDINETICLOPIDINE

1)1) Interferes with platelet-fibrinogen binding Interferes with platelet-fibrinogen binding 2)2) Exerts its action for the life of the plateletExerts its action for the life of the platelet3)3) May prolong bleeding timeMay prolong bleeding time4)4) Useful for coronary artery stents and CVA Useful for coronary artery stents and CVA

((cerebrovascular accidentcerebrovascular accident ))5)5) Methylprednisolone may reverse its effectMethylprednisolone may reverse its effect6)6) Associated with TTP (Associated with TTP (thrombocytopenic thrombocytopenic

purpurapurpura), neutropenia, and diarrhea ), neutropenia, and diarrhea

CLOPIDOGRELCLOPIDOGREL

1)1) Interferes with GP IIb/IIIa Interferes with GP IIb/IIIa

((Glycoprotein IIbGlycoprotein IIb// IIIa IIIa ) binding site ) binding site

2)2) Exerts its action for the life of the Exerts its action for the life of the plateletplatelet

3)3) May prolong bleeding timeMay prolong bleeding time

4)4) Indicated for prevention of MI, CVA, and Indicated for prevention of MI, CVA, and vascular deathvascular death

5)5) Fewer side effects than ticlopidineFewer side effects than ticlopidine

6)6) Dose: 75 mg daily Dose: 75 mg daily

Abciximab (ReoPro)Abciximab (ReoPro)

1)1) Human-mouse monoclonal antibodies Human-mouse monoclonal antibodies

2)2) Binds to GP IIb/IIIa receptor on plateletsBinds to GP IIb/IIIa receptor on platelets

3)3) Half-life 10 min.Half-life 10 min.

4)4) May block receptor for 10 daysMay block receptor for 10 days

5)5) Indicated for prevention of closure of Indicated for prevention of closure of coronary vessels after angioplastycoronary vessels after angioplasty

6)6) May cause thrombocytopeniaMay cause thrombocytopenia

7)7) Used with heparin and ASAUsed with heparin and ASA

Ant platelet Ant platelet therapytherapy

Recombinant Human Recombinant Human Activated Protein CActivated Protein C

Drotrecogin alfa (activated)- XigrisDrotrecogin alfa (activated)- Xigris Indicated for Severe Sepsis in Adults Indicated for Severe Sepsis in Adults

with Acute Organ Dysfunction with with Acute Organ Dysfunction with High Risk of DeathHigh Risk of Death

Reduction in Death as Primary End Reduction in Death as Primary End Point Point

Antithrombotic, Antiinfammatory, Antithrombotic, Antiinfammatory, Profibrinolytic PropertiesProfibrinolytic Properties

Serious Bleeding is Major Side EffectSerious Bleeding is Major Side Effect

Antithrombin III Inhibits the Following Antithrombin III Inhibits the Following Serine ProteasesSerine Proteases

CoagulationCoagulation

Factor XIIaFactor XIIa Factor XIaFactor XIa Factor IXaFactor IXa Factor XaFactor Xa ThrombinThrombin

FibrinolysisFibrinolysis

PlasminPlasmin

Inhibitory activity against all these enzymes is substantially accelerated by heparin

HEPARINHEPARIN (Description) (Description)

1)1) Discovered in 1916 by McLean; isolated from Discovered in 1916 by McLean; isolated from liver, thus the name heparinliver, thus the name heparin

2)2) Anionic glycosaminoglycan available as calcium or Anionic glycosaminoglycan available as calcium or sodium salt, negative chargesodium salt, negative charge

3)3) Molecular weight 15,000 D (avg.) (3000-30000 D)Molecular weight 15,000 D (avg.) (3000-30000 D)

4)4) Prepared from porcine intestinal mucosa and Prepared from porcine intestinal mucosa and bovine lungbovine lung

5)5) Does not cross placentaDoes not cross placenta

6)6) Little interaction with other medicationsLittle interaction with other medications

7)7) IV or SC administration onlyIV or SC administration only

8)8) Reversible with protamine sulfate (1 mg/200 U Reversible with protamine sulfate (1 mg/200 U

heparin) heparin)

HeparinHeparin

About 1/3 of dose binds to AT IIIAbout 1/3 of dose binds to AT III To form the AT III:Heparin:Clotting To form the AT III:Heparin:Clotting

Factor Complex- requires Factor Complex- requires at leastat least 18 18 saccarides saccarides exceptexcept

Unique high affinity pentasaccaride Unique high affinity pentasaccaride heparin sequences catalyze inhibition heparin sequences catalyze inhibition of Xa by ATof Xa by AT

HEPARIN (Action) HEPARIN (Action)

1)1) Binds to and potentiates Binds to and potentiates

antithrombin IIIantithrombin III

2)2) Heparin-antithrombin III complex Heparin-antithrombin III complex inactivates thrombin (factor IIa) and inactivates thrombin (factor IIa) and factor Xa (Stuart-Prover)factor Xa (Stuart-Prover)

3)3) Secondary effect against platelet Secondary effect against platelet functionfunction

Monitoring of Anticoagulant Monitoring of Anticoagulant TherapyTherapy with Heparinwith Heparin

HeparinHeparins.q. – no monitoring requireds.q. – no monitoring requiredi.v. - i.v. - APTT APTT Activated Partial Thromboplastin TimeActivated Partial Thromboplastin Time

i. v. - no less than 4 times daily or more i. v. - no less than 4 times daily or more frequent if PTT variesfrequent if PTT variestherapeutic goaltherapeutic goal – 2-2.5 times normal – 2-2.5 times normal control value (-30 sec)control value (-30 sec)

HEPARIN (Indications)HEPARIN (Indications)

Full Dose:Full Dose: 5000 U or 80 U/kg 5000 U or 80 U/kg IVIV bolus, followed by 1200-1600 bolus, followed by 1200-1600 U/hr adjusted to therapeutic range U/hr adjusted to therapeutic range 1)1) Acute deep venous thrombosisAcute deep venous thrombosis 2)2) Pulmonary emboliPulmonary emboli 3)3) Unstable angina and myocardial infarctionUnstable angina and myocardial infarctionLow Dose:Low Dose: 5000 U 5000 U sqsq q12 h q12 h 1)1) Postoperative prophylaxis of any major abdominal, Postoperative prophylaxis of any major abdominal, thoracic, gynecologic, or orthopedic procedurethoracic, gynecologic, or orthopedic procedure 2)2) Immobilized medical patients >40 yrs. with CHF, CVA, Immobilized medical patients >40 yrs. with CHF, CVA,

malignant diseasemalignant disease 3)3) Prophylaxis for underlying hypercoagulable stateProphylaxis for underlying hypercoagulable stateOther Dose:Other Dose: 1)1) Extracorporeal bypassExtracorporeal bypass 2)2) HemodialysisHemodialysis 3)3) AfterAfter thrombolytic therapy thrombolytic therapy

HeparinHeparin

Pregnancy- YESPregnancy- YES

HEPARIN (Contraindications)HEPARIN (Contraindications)

11)) ThrombocytopeniaThrombocytopenia2)2) Aspirin or alcohol useAspirin or alcohol use3)3) Hepatic or renal diseaseHepatic or renal disease4)4) Other platelet dysfunctionOther platelet dysfunction5)5) GI bleedingGI bleeding6)6) TumorsTumors

HEPARIN (Side Effects)HEPARIN (Side Effects)

1)1) Major side effect is bleedingMajor side effect is bleeding

2)2) Osteoporosis with prolonged Osteoporosis with prolonged useuse

3)3) ThrombocytopeniaThrombocytopenia

HEPARIN-INDUCED THROMBOCYTOPENIAHEPARIN-INDUCED THROMBOCYTOPENIA 1)1) Occurs in 2-5% of patients receiving standard Occurs in 2-5% of patients receiving standard

heparin by immune mechanismheparin by immune mechanism

2)2) May occur with minute doses, including heparin May occur with minute doses, including heparin flushesflushes

3)3) More common with bovine than porcine heparinMore common with bovine than porcine heparin

4)4) Asymptomatic thrombocytopenia can occur in 30-Asymptomatic thrombocytopenia can occur in 30-50% of pts who develop HIT antibodies 50% of pts who develop HIT antibodies

5)5) ~~20-50% of thrombocytopenic patients develop 20-50% of thrombocytopenic patients develop arterial or venous thrombosis that may be life arterial or venous thrombosis that may be life threatening threatening

HEPARIN-INDUCED THROMBOCYTOPENIAHEPARIN-INDUCED THROMBOCYTOPENIA

1)1) Usually appears 3-15 days after Usually appears 3-15 days after starting heparin, peak incidence starting heparin, peak incidence day 8 day 8

2) Diagnosis is largely clinical despite 2) Diagnosis is largely clinical despite availability of several tests used to availability of several tests used to attempt confirmationattempt confirmation

1)1) LepirudinLepirudin

2)2) Argatroban Argatroban

HEPARIN-INDUCED HEPARIN-INDUCED THROMBOCYTOPENIA THROMBOCYTOPENIA

Alternative AnticoagulantsAlternative Anticoagulants

LEPIRUDIN LEPIRUDIN

1)1) Recombinant form of hirudinRecombinant form of hirudin

2)2) Highly specific direct thrombin Highly specific direct thrombin inhibitorinhibitor

3)3) Short half-life 1-2 hoursShort half-life 1-2 hours

4)4) Monitored by APTT Monitored by APTT

5)5) Crosses placenta in rats, would not Crosses placenta in rats, would not use in pregnancy at present use in pregnancy at present

6)6) No antidoteNo antidote

LOW MOLECULAR WEIGHT LOW MOLECULAR WEIGHT HEPARINHEPARIN

1) 1) Molecular weight 3,000- 7,000 DMolecular weight 3,000- 7,000 D

2)2) Inhibits factor Xa rather than thrombinInhibits factor Xa rather than thrombin

3)3) Factor Xa assay used for monitoring Factor Xa assay used for monitoring

4)4) Administered subcutaneously 2 times/dAdministered subcutaneously 2 times/d

5)5) Probably less antigenic than standard Probably less antigenic than standard heparinheparin

6)6) Recommended for prophylaxis and Recommended for prophylaxis and treatmenttreatment

LOW MOLECULAR WEIGHT LOW MOLECULAR WEIGHT HEPARINHEPARIN

1) 1) PT, APTT not usually prolongedPT, APTT not usually prolonged

2) 2) May be monitored with anti-factor Xa May be monitored with anti-factor Xa assayassay

LOW MOLECULAR WEIGHT LOW MOLECULAR WEIGHT HEPARINSHEPARINS

Indications for and Contraindications toIndications for and Contraindications to Parenteral Anticoagulant Agents Parenteral Anticoagulant Agents

Anticoagulant Anticoagulant AgentAgent

ClassClass Approved & Appropriate Approved & Appropriate IndicationsIndications

ContraindicatioContraindicationn

Unfractionated Unfractionated heparinheparin

EnoxaparinEnoxaparin((LovenoxLovenox))

DalteparinDalteparin((FragminFragmin))

TinzaparinTinzaparin((InnohepInnohep))

AntithromAntithrombin III bin III inhibitorinhibitor

Low-Low-molecular-molecular-weight weight heparinheparin

Low-Low-molecular-molecular-weight weight heparinheparin

Low-Low-molecular-molecular-weight weight heparinheparin

Treatment of venous Treatment of venous thromboembolism or thromboembolism or unstable angina; used unstable angina; used when rapid reversal is when rapid reversal is importantimportant

Prophylaxis in Prophylaxis in moderate-risk or high-moderate-risk or high-risk patients, risk patients, treatment of venous treatment of venous thromboembolism or thromboembolism or unstable anginaunstable angina

Prophylaxis in Prophylaxis in moderate-risk or high-moderate-risk or high-risk patients, risk patients, treatment of venous treatment of venous thromboembolism or thromboembolism or unstable anginaunstable angina

Prophylaxis in Prophylaxis in moderate-risk or high-moderate-risk or high-risk patients, risk patients, treatment of venous treatment of venous thromboembolismthromboembolism

?Prophylactic ?Prophylactic treatmenttreatment

Regional Regional anesthesiaanesthesia

PregnancyPregnancy

Prosthetic Heart Prosthetic Heart ValvesValves

Regional Regional anesthesiaanesthesia

Regional Regional anesthesiaanesthesia

Heparin-Antibiotic InteractionsHeparin-Antibiotic Interactions

The cephalosporins- The cephalosporins- cefamandole, cefotetan, cefamandole, cefotetan, and cefoperazoneand cefoperazone, contain an N-, contain an N-methylthiotetrazole (NMTT) side chain. This methylthiotetrazole (NMTT) side chain. This NMTT group can:NMTT group can:

- Dissociate from the parent antibiotic in solution - Dissociate from the parent antibiotic in solution or in vivo and or in vivo and competitively inhibit vitamin K competitively inhibit vitamin K action, leading to prolongation of the action, leading to prolongation of the prothrombin time and bleeding. prothrombin time and bleeding.

- This side chain is also associated with a - This side chain is also associated with a disulfiram-like reaction to alcoholdisulfiram-like reaction to alcohol..

- Clinical bleeding has been less frequently - Clinical bleeding has been less frequently reported with Cefotetan than with reported with Cefotetan than with cefoperazone or cefamandole.cefoperazone or cefamandole.

ANTICOAGULANTS ANTICOAGULANTS

OF INDIRECT ACTIONOF INDIRECT ACTION

COUMARIN (Description)COUMARIN (Description)

1)1) Isolated by Link in 1939 after previous Isolated by Link in 1939 after previous observation that cattle developed observation that cattle developed

bleeding bleeding disorder after ingestion of disorder after ingestion of spoiled cloverspoiled clover2)2) Is 4-hydroxycoumarin compound, similar Is 4-hydroxycoumarin compound, similar in in structure to vitamin Kstructure to vitamin K3)3) Administered p.o., rapid GI absorptionAdministered p.o., rapid GI absorption4)4) Crosses placenta easily (complications!)Crosses placenta easily (complications!)5)5) Interacts with a variety of drugsInteracts with a variety of drugs

COUMARIN (Actions)COUMARIN (Actions)

1)1) Blocks the carboxylation of the Blocks the carboxylation of the vitamin K dependent clotting vitamin K dependent clotting proteins, factors II, VII, IX, and X, proteins, factors II, VII, IX, and X, maintaining them in their maintaining them in their inactive formsinactive forms

2) Blocks the anticoagulant proteins 2) Blocks the anticoagulant proteins C and S C and S

3) Onset – 18-48 hours3) Onset – 18-48 hours

PLASMA HALF-LIVES OF VITAMIN K PLASMA HALF-LIVES OF VITAMIN K DEPENDENT CLOTTING FACTORSDEPENDENT CLOTTING FACTORS

HoursHours Factor IIFactor II 6060 Factor VIIFactor VII 66 Factor IXFactor IX 2424 Factor XFactor X 3030 Protein CProtein C 66 Protein SProtein S 4242

COUMARIN COUMARIN LaboratoryLaboratory

1)1) Prolongs the PT and APTTProlongs the PT and APTT

2)2) PT and Prothrombin index -used PT and Prothrombin index -used for monitoring for monitoring

Prothrombin indexProthrombin index INTERNATIONAL NORMALIZED RATIO INTERNATIONAL NORMALIZED RATIO

(INR)(INR)

INR = INR = PATIENT PTPATIENT PT

CONTROL PTCONTROL PT

COUMARIN COUMARIN Side EffectsSide Effects

1)1) HemorrhageHemorrhage

2) Fetal abnormalities2) Fetal abnormalities

3)3) Skin necrosis with deficiencies of Skin necrosis with deficiencies of proteins proteins C or S usually on 3rd to 8th C or S usually on 3rd to 8th day of therapyday of therapy

COUMARIN-INDUCED COUMARIN-INDUCED SKIN NECROSISSKIN NECROSIS

1)1) Usually occurs on days 3-8 after Usually occurs on days 3-8 after initiation of Coumarin initiation of Coumarin

2) 2) More common in females (75%)More common in females (75%)

3)3) Most common on the breast, Most common on the breast, buttocks, or extremities, occ. on buttocks, or extremities, occ. on penis in malespenis in males

4)4) Not predictable by history or Not predictable by history or protein C levelprotein C level

COUMARINCOUMARIN InteractionsInteractionsPOTENTIATORS:POTENTIATORS:

PhenylbutazonePhenylbutazoneCimetidineCimetidineOmeprazoleOmeprazoleAmiodaroneAmiodaroneAnabolic steroidsAnabolic steroids

ANTAGONISTS:ANTAGONISTS:BarbituratesBarbituratesRifampinRifampinPenicillinsPenicillinsAntacidsAntacids

WarfarinWarfarin

Pregnancy- NOPregnancy- NO

Contraindication towards administration of Contraindication towards administration of anticoagulants of indirect actionanticoagulants of indirect action

Hemorrhagic diathesesHemorrhagic diatheses Ulcer of stomach and duodenumUlcer of stomach and duodenum Ulcerative colitisUlcerative colitis Pregnancy Pregnancy Malignant formationsMalignant formations Disturbance of functions of Disturbance of functions of

kidneys, liverkidneys, liver

Mechanism of action of thrombolytic Mechanism of action of thrombolytic agentsagents

Blood plasmaBlood plasma Thrombus Thrombus Profibrinolysin (plasminogen)

Fibrinolysin (plasmin)

Decomposition products Fibrinogen

Profibrinolysin (plasminogen)

Fibrin

Fibrinolysin (plasmin)

Fibrin Decomposition

products

StreptokinaseStreptokinase++profibrinolysinprofibrinolysin

Urokinase Urokinase

Activators

Tissue activator of Tissue activator of profibrinolysinprofibrinolysin

+ +

++

+

Pharmacodynamics of fibrinolytic drugsPharmacodynamics of fibrinolytic drugs

After introduction into organism they After introduction into organism they cause lyses of cause lyses of freshfresh (24-72 (24-72 hourshours) ) thrombi in arteries, veins, cavitiesthrombi in arteries, veins, cavities

The most effective during the first 2-3 The most effective during the first 2-3 hours after initiation of thrombosishours after initiation of thrombosis

Administration of fibrinolyticsAdministration of fibrinolytics

ThrombosisThrombosis, , thromboembolia ofthromboembolia of:: -- lungslungs - - brainbrain - - eye retina eye retina

Myocardium infarctionMyocardium infarction

Thromboses of profound veinsThromboses of profound veins

Heparin often used after initial thrombolytic therapyHeparin often used after initial thrombolytic therapy

Side effects of fibrinolyticsSide effects of fibrinolytics

HemorrhagesHemorrhages ((prothrombine index prothrombine index ((decreasing no less than decreasing no less than 30-40 %),30-40 %), clotting clotting timetime ((increasing no moreincreasing no more than 2 times), than 2 times), fibrinogen content (notfibrinogen content (not <<1 1 hh\\ll)) should be should be under the constant control)under the constant control)

Allergic reactionsAllergic reactions ( (face hyperemiaface hyperemia, , abdominal pain, pain behind the sternum, abdominal pain, pain behind the sternum, chillchill, , raised body temperatureraised body temperature – – these are these are reactions on foreign proteinreactions on foreign protein))

ContraindicationsContraindications:: hemorrhagic diatheseshemorrhagic diatheses, , hemorrhageshemorrhages. . Open wounds, ulcer diseaseOpen wounds, ulcer disease. . Nephritis, acute form ofNephritis, acute form of tbctbc, , x-ray disease.x-ray disease.

HaemostaticsHaemostatics

Drugs which promote Drugs which promote hemorrhages stoppage hemorrhages stoppage

((haemostatichaemostatic)) 1. 1. Natural components of blood clotting and Natural components of blood clotting and

drugs which promote their productiondrugs which promote their production а) а) drugs of local actiondrugs of local action ( (thrombin, haemostatic sponge, fibrin filmthrombin, haemostatic sponge, fibrin film б) б) drugs of systemic actiondrugs of systemic action ( (fibrinogenfibrinogen, , vitamin vitamin К, К, vikasolvikasol, , calcium calcium

chloridechloride))

2. 2. Antifibrinolytic drugsAntifibrinolytic drugs ( (fibrinolysis inhibitorsfibrinolysis inhibitors)) а) а) of direct actionof direct action ( (contrical, trasisol, tzalol, gordoxcontrical, trasisol, tzalol, gordox)) б) б) of intermediated action:of intermediated action: aminocapronic acid, tranexamic acidaminocapronic acid, tranexamic acid, ,

ambenamben ( (pambapamba)) 3. 3. Drugs which increase blood viscosityDrugs which increase blood viscosity ((medical medical

gelatingelatin))

4. 4. AngioprotectorsAngioprotectors а) а) syntheticsynthetic ( (ethamzilateethamzilate, , Ca dobesilat, androxonCa dobesilat, androxon)) б) б) of plantof plant origin origin ((nettle - Urticanettle - Urtica, , cortex Viburnicortex Viburni, , herba Polygoni, herba herba Polygoni, herba

ArnicaeArnicae))

Thrombin – only topical !!!Thrombin – only topical !!!

HAEMOSTATICS HAEMOSTATICS with systemic actionwith systemic action

FibrinogenFibrinogen, , Calcium chlorideCalcium chloride, , vitamin vitamin К, К, VikasolumVikasolum

INHIBITORS OF FIBRINOLYSISINHIBITORS OF FIBRINOLYSISof direct action (Contrical, Trasilol, Gordox)of direct action (Contrical, Trasilol, Gordox)

of indirect action of indirect action ((Ac aminocapronicum, Ac. Ac aminocapronicum, Ac. tranexamicumtranexamicum, , AmbenAmben))

VASOPROTECTORSVASOPROTECTORS

EthamsilateEthamsilate

Stabilize the walls of vesselsStabilize the walls of vessels

Urtica (Nettle)Urtica (Nettle)

Viburnum (Snow ball, Viburnum (Snow ball, Water elder)Water elder)

Arnica (arnica)Arnica (arnica)

Polygonum hydropiperPolygonum hydropiper (Water pepper)(Water pepper)

Hippocastanum (Aescusan)Hippocastanum (Aescusan)(Horse chestnut)(Horse chestnut)

Ginkgo bilobaGinkgo biloba(Maidenhair-tree)(Maidenhair-tree)

TanakanTanakan

DRUGS AFFECTING DRUGS AFFECTING HAEMOPOESISHAEMOPOESIS

Food products with ironFood products with iron

MeatMeatSoybeansSoybeans

Dry smoked plumsDry smoked plumsSpinachSpinach

Dry apricotsDry apricotsBuckwheatBuckwheat

RiceRiceBreadBread

Fruits of Fruits of pomegranate pomegranate

Iron from animal products absorbs much Iron from animal products absorbs much more better than from plants (more better than from plants (22 %22 % and 1 % and 1 %))

DRUGS EFFECTING DRUGS EFFECTING HAEMOPOESISHAEMOPOESIS

Combined drugsCombined drugsActiferrin Actiferrin Iron sulfateIron sulfate, , D,L- serinD,L- serin

Iron sulfateIron sulfate, , D,L- serinD,L- serin, , glucoseglucose, , fructosefructoseCapsCaps., 11385 ., 11385 gg

syrupsyrup 5 5 mlml – 171 – 171 mgmg

34,5 34,5 mgmg

34 34 mgmg

Sorbifer-durulesSorbifer-durules Iron sulfate, ascorbatic acidIron sulfate, ascorbatic acid TabTab., 320 ., 320 mgmg 100 100 mgmg

Ferrplect Ferrplect Iron sulfate, ascorbatic acidIron sulfate, ascorbatic acid TabTab., 50 ., 50 mgmg 10 10 mgmg

Ferroplex Ferroplex Iron sulfate, ascorbatic acidIron sulfate, ascorbatic acid TabTab., 50 ., 50 mgmg 10 10 mgmg

Fefol Fefol Iron sulfate, folic acidIron sulfate, folic acid TabTab., 150 ., 150 mgmg 47 47 mgmg

Ferro-folgammaFerro-folgamma Iron sulfate, folic acid, vitIron sulfate, folic acid, vit. В. В1212 CapsCaps., 100 ., 100 mgmg 20 20 mgmg

Tardiferron-retardTardiferron-retard Iron sulfate, ascorbatic acid, Iron sulfate, ascorbatic acid, mucoproteasemucoprotease

DrageeDragee, 256,3 , 256,3 mgmg

80 80 mgmg

Gyno-tardiferronGyno-tardiferron Iron sulfate, ascorbatic acid, Iron sulfate, ascorbatic acid, mucoprotease, folic acidmucoprotease, folic acid

DrageeDragee, 256, , 256, 33mgmg

80 80 mgmg

Fenulse Fenulse Iron sulfate, ascorbatic acid, Iron sulfate, ascorbatic acid, nicotinamid, vitamins of B groupnicotinamid, vitamins of B group

CapsulesCapsules 45 45 mgmg

Irovit Irovit Iron sulfate, ascorbatic acid, folic Iron sulfate, ascorbatic acid, folic acid, ciancobalamine, lysineacid, ciancobalamine, lysine

CapsCaps., 300 ., 300 mgmg 100 100 mgmg

Ferrostab Ferrostab Iron fumarateIron fumarate, , folic acidfolic acid TabTab., 154 ., 154 mgmg 33 %33 %

Folfetab Folfetab Iron fumarate, folic acidIron fumarate, folic acid TabTab., 200 ., 200 ,mg,mg 33 %33 %

Globiron Globiron Iron fumarate, folic acid, vitt.Iron fumarate, folic acid, vitt. В В66, В, В1212.. Caps.Caps.

Macrofer Macrofer Iron gluconate, folic acidIron gluconate, folic acid TabTab., 625 ., 625 mgmg 12 %12 %

Iron SULFATEIron SULFATE ( (gradumet gradumet substancesubstance))

Iron SULFATEIron SULFATE++ascorbatic ascorbatic acidacid++mucoproteasemucoprotease

Iron SULFATEIron SULFATE++ascorbatic ascorbatic acidacid++mucoproteasemucoprotease

Iron SULFATEIron SULFATE++ascorbatic acidascorbatic acid

Iron SULFATEIron SULFATE++ascorbatic acidascorbatic acid

Multofer Multofer ((FeFe3+ 3+ -hydroxide polymaltose complex)-hydroxide polymaltose complex)

Iron asparginateIron asparginate ( (FeFe3+3+))

Iron fumarate Iron fumarate

Criteria of iron drugs therapy Criteria of iron drugs therapy effectivenesseffectiveness

Increasing of reticulocytes quantity onIncreasing of reticulocytes quantity on 5-7 5-7th day after th day after administrationadministration

Normalization of blood iron-binding function indexesNormalization of blood iron-binding function indexes ( (not not only indexes of peripheral bloodonly indexes of peripheral blood))

If the latter get normalized during If the latter get normalized during 1-2 1-2 months of therapymonths of therapy, , than saturationthan saturation of depot get normalized onof depot get normalized on 3 3rd monthrd month.. On On this stagethis stage dose of the drugs must be decreased to dose of the drugs must be decreased to 60-80 60-80 mgmg of elementaryof elementary FFе е per 2 hoursper 2 hours..

If the reason of blood loss has been eliminated If the reason of blood loss has been eliminated administration of the drugs is determined by iron administration of the drugs is determined by iron metabolism indexesmetabolism indexes. .

If the reason of iron loss is not eliminated supportive If the reason of iron loss is not eliminated supportive therapy is carried on according to the following: therapy is carried on according to the following: 20-40 20-40 mg of mg of elementaryelementary FeFe per day during a week and afterper day during a week and after 3-4 3-4 weeks weeks of brake and so on.of brake and so on.

Complications of therapy with Complications of therapy with peroral peroral

iron drgusiron drgus

Activation of free-radical Activation of free-radical processesprocesses

Nausea, vomiting, diarrheaNausea, vomiting, diarrhea ((irritation of mucous membranesirritation of mucous membranes))

Constipations Constipations ((FeS productionFeS production))

Melena Melena Black coloring of teethBlack coloring of teeth Appearance of metallic taste in Appearance of metallic taste in

the mouththe mouth

Indications towards administration of Indications towards administration of parenteral forms of ironparenteral forms of iron

Condition after gastrectomyCondition after gastrectomy Condition after massive resection Condition after massive resection

of small intestineof small intestine Heavy enteritisHeavy enteritis Parenteral nutritionParenteral nutrition Haemodyalysis Haemodyalysis Psychogenic anorexiaPsychogenic anorexia

Drugs for parenteral introductionDrugs for parenteral introduction

Ferbitol Ferbitol Chelate substancesChelate substances AmpAmp., 1 ., 1 mlml i.m.i.m.

50 50 mgmg

Ferlecyt Ferlecyt Chelate substancesChelate substances

Sodium gluconate complexSodium gluconate complex

AmpAmp., 1 ., 1 mlml i.m.i.m.

AmpAmp., 5 ., 5 mlml i.v.i.v.

50 50 mgmg

100 100 mgmg

Fercoven Fercoven Polynuclear hydroxyl complexes Polynuclear hydroxyl complexes of ironof iron, , saccharate of ironsaccharate of iron, , gluconate of cobaltgluconate of cobalt

AmpAmp., 1 ., 1 mlml i.v.i.v.

20 20 mgmg

ЖектоферЖектофер Polynuclear hydroxyl complexes Polynuclear hydroxyl complexes of iron, sorbitol, citric acidof iron, sorbitol, citric acid AmpAmp., 2 ., 2 mlml

i.m.i.m.100 100 mgmg

Ferrum-lekFerrum-lek Polynuclear hydroxyl complexes Polynuclear hydroxyl complexes of ironof iron. . Polymaltose complexPolymaltose complex

AmpAmp., 2 ., 2 mlml i.m.i.m. Amp., Amp., 5 5 ml ml i.v.i.v.

100 100 mgmg

100 100 mgmg

Maltofer Maltofer -\\--\\- AmpAmp., 2 ., 2 mlml i.m.i.m.

100 100 mgmg

Venofer Venofer -\\--\\- AmpAmp., 5 ., 5 mlml i.v.i.v.

100 100 mgmg

Polynuclear hydroxyl complexes of Polynuclear hydroxyl complexes of

ironiron ((polyisomaltosate of ironpolyisomaltosate of iron))

Calculation of dose of drugs for Calculation of dose of drugs for parenteral introductionparenteral introduction

А=КА=Кхх(100-6(100-6HbHb))хх0,0066,0,0066, wherewhere А – А – quantity of ampoules of drug with quantity of ampoules of drug with contents ofcontents of 100 100 mg ofmg of Fe Fe (per treatment coarse(per treatment coarse););

К – К – patient’s body weightpatient’s body weight ( (kgkg););

HbHb – – contents of hemoglobin in gcontents of hemoglobin in g % %

А=(КА=(Кхх2,5)2,5)хх [16,5-(1,3Hb)][16,5-(1,3Hb)],,wherewhere А – А – quantity of ironquantity of iron mg per coarsemg per coarse;;

К – К – body weightbody weight ( (kgkg););

HbHb – – contents of hemoglobincontents of hemoglobin ( (gg\100 \100 mlml))More than 100 mg of elementary iron per day should not be More than 100 mg of elementary iron per day should not be introducedintroduced

Complications which develop Complications which develop during parenteral iron introductionduring parenteral iron introduction

PhlebitisPhlebitis, , after-injection abscesses, pain in the place of after-injection abscesses, pain in the place of introductionintroduction; ;

Allergic reactionsAllergic reactions;; Hyperemia of face, neck, feeling of pressure behind Hyperemia of face, neck, feeling of pressure behind

sternum, pain in lumbal area, sternocardiasternum, pain in lumbal area, sternocardia ((can be can be relieved with analgesicsrelieved with analgesics+0,5 +0,5 ml of atropine sulfateml of atropine sulfate););

Arterial hypotoniaArterial hypotonia;; Darkening of skin in place of introductionDarkening of skin in place of introduction..

ContraindicationsContraindications:: hemochromatosishemochromatosis, , liver diseasesliver diseases, , coronary insufficiencycoronary insufficiency, , essential hypertension ofessential hypertension of ІІ – ІІІ ІІ – ІІІ stagesstages,, acute nephritis acute nephritis..

In case of acute poisoningIn case of acute poisoning with iron drugswith iron drugs deferroxamine and EDTA are introduceddeferroxamine and EDTA are introduced

Hyperchrome anemiaHyperchrome anemia

а) а) megaloblastmegaloblast Erythroblast Erythroblast Hyperchrome megaloblastHyperchrome megaloblast

MegalocyteMegalocyteCyanocobalamine, oxycobalamineCyanocobalamine, oxycobalamine ( (are transformed are transformed

into cobamamid) and folic acid are introducedinto cobamamid) and folic acid are introduced..

б)б) macrocytar macrocytar ErythroblastErythroblast Hyperchrome macronormoblast Hyperchrome macronormoblast

MacrocyteMacrocyteFolic acid is usedFolic acid is used

Erythremia Erythremia ((polycytemiapolycytemia))

Anti-blastoma drug Anti-blastoma drug imifodimifod and and radioactive isotopes of phsophorus radioactive isotopes of phsophorus ((3232Р)Р) are used are used

Other drugs used for hypochrome Other drugs used for hypochrome anemiaanemia

Cobalt drusCobalt drus ((coamidcoamid)) Human recombinant erythropoetinHuman recombinant erythropoetin

((eportineportin alfaalfa, , epogenepogen, , eprexeprex))

Leucopoesis stimulantsLeucopoesis stimulants

Mechanism of action is based on their participation in Mechanism of action is based on their participation in piramidine bases synthesispiramidine bases synthesis, , which are necessary for synthesis which are necessary for synthesis of nucleonic acidsof nucleonic acids

DrugsDrugs:: - - methyluracylmethyluracyl ((doesn’t have irritative action, ways of doesn’t have irritative action, ways of

introduction; perorally, rectally locally)introduction; perorally, rectally locally);; - - pentoxylpentoxyl ( (possesses irritative action, administered possesses irritative action, administered

perorally after a meal, with milkperorally after a meal, with milk);); - - sodium nucleonatesodium nucleonate ( (introduced perorally and i.m., introduced perorally and i.m.,

possesses irritative activity)possesses irritative activity).. Nowadays also stimulants of new type were synthesizedNowadays also stimulants of new type were synthesized – –

activators of colony-producing factor of leucopoesisactivators of colony-producing factor of leucopoesis:: - - molgramostim molgramostim ((granulocyte-macrophagal colony-stimulating granulocyte-macrophagal colony-stimulating

factor andfactor and - - filgrastimfilgrastim ( (granulocytar colony-producing factorigranulocytar colony-producing factori))

Folic acidFolic acid

Folic acidFolic acid

Drugs which depress leucopoesisDrugs which depress leucopoesis

Are administered in case of leucosis and Are administered in case of leucosis and lymphogranulomatosislymphogranulomatosis

Antiblastome drugs refer to this groupAntiblastome drugs refer to this group:: - - methotrexatemethotrexate - - merkaptopurinemerkaptopurine - - chlorbutinchlorbutin - - mielosanmielosan - - vinblastinvinblastin - - vinkristinvinkristin