DRUGS AFFECTING THE BLOOD

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Drugs Affecting Blood

Treatment of Treatment of AnemiaAnemia ThrombosisThrombosis BleedingBleeding

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Drugs used to treat thrombotic disorders

AnticoagulantsAnticoagulants

ThrombolyticsThrombolytics

Drugs for treatment of anemia

Vitamin B12Vitamin B12 ErythropoietinErythropoietin Folic acidFolic acid Iron Iron

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Drugs for treatment of bleeding

Aminocaproic acidAminocaproic acid EnoxaparinEnoxaparin HeparinHeparin WarfarinWarfarin Lepirudin Lepirudin

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Platelet Response To Vascular Injury

Platelet adhesion to site of vascular injury Platelet adhesion to site of vascular injury Activation of platelets by factors that include Activation of platelets by factors that include

TxA2, ADP, serotonin, collagen & thrombin TxA2, ADP, serotonin, collagen & thrombin Increase expression of glycoprotein IIb/IIIa Increase expression of glycoprotein IIb/IIIa

receptors receptors Aggregation of platelets by a cross-linking Aggregation of platelets by a cross-linking

reaction due to fibrinogen binding to glycoprotein reaction due to fibrinogen binding to glycoprotein IIb/IIIa receptors IIb/IIIa receptors

Formation of the thrombus by fibrin monomer Formation of the thrombus by fibrin monomer cross link. cross link.

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Platelet aggregation inhibitors

These agents are beneficial in the These agents are beneficial in the prevention and treatment of occlusive prevention and treatment of occlusive cardiovascular diseasescardiovascular diseases

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Antiplatelet drugs

Aspirin Aspirin Ticlopidine and clopidogrealTiclopidine and clopidogreal Abciximab Abciximab Tirofiban and eptifibatideTirofiban and eptifibatide Dipyridamole Dipyridamole

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Platelet Inhibitors AspirinAspirin

Blocks Blocks cyclooxygenase 1, cyclooxygenase 1, inhibiting the inhibiting the formation of formation of thromboxane A2thromboxane A2

Arachidonic Acid

Prostaglandins, Thromboxane

CyclooxygenaseCyclooxygenase

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ASPIRIN

Used as prophylactic in treatment of TIA & Used as prophylactic in treatment of TIA & atrial fibrillation.atrial fibrillation.

Low dose: prevent incidence of MI and Low dose: prevent incidence of MI and recurrencerecurrence

SE; GI disturbanceSE; GI disturbance, Bleeding Time , Bleeding Time prolonged. prolonged.

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TiclopidineTiclopidine Inhibits the binding of ADP Inhibits the binding of ADP to its to its

receptor on platelet resulting in a receptor on platelet resulting in a ↓ in ↓ in platelet aggregation and thrombus platelet aggregation and thrombus formationformation

Very effective (adverse effect: Very effective (adverse effect: neutropenianeutropenia))

ClopidogrelClopidogrel – NEWER DRUG (same – NEWER DRUG (same mechanism- no neutropenia)mechanism- no neutropenia)

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Abciximab, Eptifibatide & Tirofiban

Tirofiban & EptifibatideTirofiban & Eptifibatide: antagonists : antagonists of glycoprotein IIb/IIIa receptors –of glycoprotein IIb/IIIa receptors –

decrease aggregation by preventing decrease aggregation by preventing cross- linking reaction.cross- linking reaction.

AbxicimabAbxicimab: is a monoclonal antibody that : is a monoclonal antibody that binds to GPIIb/IIIa preventing platelet binds to GPIIb/IIIa preventing platelet aggregationaggregation

Anticoagulants

Are drugs used to treat and prevent clotting Are drugs used to treat and prevent clotting via inhibition of various steps in the via inhibition of various steps in the coagulation pathway which involves two coagulation pathway which involves two interrelated pathways called the interrelated pathways called the intrinsicintrinsic and and extrinsic pathwayextrinsic pathway

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Heparin

Binds to antithrombin III Binds to antithrombin III in blood causing rapid in blood causing rapid inactivation of factors IIa inactivation of factors IIa & Xa (mainly).& Xa (mainly).

Heparin is a large Heparin is a large polysaccharides given polysaccharides given IV/SC. IV/SC.

No placental access. No placental access.

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Heparin

Effective in acute treatment ofEffective in acute treatment of Venous thrombosis prevention - post Venous thrombosis prevention - post

surgicalsurgical Deep venous thromboembolismDeep venous thromboembolism Acute myocardial infarctionAcute myocardial infarction Prevention of clotting in medical devices Prevention of clotting in medical devices

(catheters, hemodialysis, heart lung (catheters, hemodialysis, heart lung machines)machines)

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HEPARIN SE:SE: HEMORRHAGEHEMORRHAGE HYPERSENSITIVITYHYPERSENSITIVITY THROMBOSISTHROMBOSIS THROMBOCYTOPENIATHROMBOCYTOPENIA Monitor the activated partial thromboplastin timeMonitor the activated partial thromboplastin time CI – hypersensitive pts, OR BLEEDING CI – hypersensitive pts, OR BLEEDING

DISORDERS, ALCHOLICS..DISORDERS, ALCHOLICS.. Excessive Bleeding caused by heparin use can be Excessive Bleeding caused by heparin use can be

reversed with reversed with protamine sulfateprotamine sulfate

Low molecular weight Heparin LMWH e.g., enoxaparinLMWH e.g., enoxaparin Binds to antithrombin III also causing rapid Binds to antithrombin III also causing rapid

inactivation of factor Xainactivation of factor Xa Longer half-lifeLonger half-life Can be used in hospital as well as out-patient Can be used in hospital as well as out-patient

setting.setting. Given subcutaneouslyGiven subcutaneously UsesUses: same as heparin: same as heparin Adverse effectAdverse effect: same as heparin but less likely to : same as heparin but less likely to

cause HITcause HIT21

ARGATROBAN

Is a direct thrombin inhibitorIs a direct thrombin inhibitor It does not require ATIIIIt does not require ATIII Does not interact with heparin-induced Does not interact with heparin-induced

antibodiesantibodies Can be used to treat HITCan be used to treat HIT

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Lepirudin (hirudin)

Closely related to hirudin –a thrombin Closely related to hirudin –a thrombin inhibitor from leechinhibitor from leech

Lepirudin is produced in yeast cells by recombinant DNA Lepirudin is produced in yeast cells by recombinant DNA techtech

Thrombin inhibitionThrombin inhibition Property of preventing Property of preventing

coagulation of the blood.coagulation of the blood.

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Lepirudin is approved for use in patients Lepirudin is approved for use in patients with with heparin-induced heparin-induced thrombocytopenia/thrombocytopenia/thrombosisthrombosis syndromessyndromes. .

DANAPAROID

Anti-factor IIa and Xa but more an anti-XaAnti-factor IIa and Xa but more an anti-Xa Given SCGiven SC USESUSES: prophylaxis of DVT in hip : prophylaxis of DVT in hip

replacement surgeryreplacement surgery Used for HITUsed for HIT Adverse effectAdverse effect: bleeding: bleeding

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Warfarin (Coumarin)

Is an antagonist of vitamin K that prevents Is an antagonist of vitamin K that prevents gamma carboxylation reactions in hepatic gamma carboxylation reactions in hepatic synthesis of coagulation factors II, VII, IX , X, synthesis of coagulation factors II, VII, IX , X, protein C & S by protein C & S by inhibing the enzyme vit K-inhibing the enzyme vit K-epoxide reductaseepoxide reductase

No effect on factors already made by the liver No effect on factors already made by the liver – – slow onset – 24 – 48 hrs. slow onset – 24 – 48 hrs. Reversal (antagonist)Reversal (antagonist): vitamin K – Increase : vitamin K – Increase

cofactor synthesis, but slow onset; fresh frozen cofactor synthesis, but slow onset; fresh frozen plasma – rapid. plasma – rapid. 26

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Warfarin – Vitamin K-Antagonist ORALORAL Met: by liver via P450Met: by liver via P450 Effective in: Effective in: longer-term anticoagulation for longer-term anticoagulation for

thromboses, emboli, post MI, heart valve thromboses, emboli, post MI, heart valve damage & artificial heart valves caused damage & artificial heart valves caused thromboembolismthromboembolism

Monitor prothrombin timeMonitor prothrombin time

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Warfarin

Crosses placentaCrosses placentaTeratogenicTeratogenicContraindicated in pregnant womenContraindicated in pregnant women

Anticoagulation in pregnancy - Anticoagulation in pregnancy - heparinheparin

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Adverse effects: Adverse effects:

hemorrhage, skin necrosis, “purple toe” hemorrhage, skin necrosis, “purple toe” syndrome, teratogenic (bone syndrome, teratogenic (bone dysmorphogenesis). dysmorphogenesis).

Drug interaction

↑↑es warfarin level and activityes warfarin level and activity:: Aspirin, sulfonamides, cimetidine, acute Aspirin, sulfonamides, cimetidine, acute

alcohol, metronidazole e.t.c.,alcohol, metronidazole e.t.c., ↓↓es warfarin level and activityes warfarin level and activity: : Chronic alcohol ingestion, barbiturates, Chronic alcohol ingestion, barbiturates,

rifampin, griseofulvin etc.,rifampin, griseofulvin etc.,

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THROMBOLYTIC AGENTS

ALTEPLASE (t PA)ALTEPLASE (t PA) STREPTOKINASESTREPTOKINASE

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Thrombolytics

tPA (Tissue Plasminogen tPA (Tissue Plasminogen ActivatorActivator Activates plasminogen Activates plasminogen

bound to fibrinbound to fibrin

StreptokinaseStreptokinase Activates free plasminogen Activates free plasminogen

into active plasmininto active plasmin

Plasminogen

Plasmin

tPA, Streptokinase

Fibrin

FibrinDegradation

Products

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Alteplase (tPA): Alteplase (tPA): natural activator, so no natural activator, so no allergy problems; allergy problems; clot(fibrin)-specificclot(fibrin)-specific, , acting on fibrin-bound plasminogen. acting on fibrin-bound plasminogen.

StreptokinaseStreptokinase: acts on bound & free : acts on bound & free plasminogen plasminogen

Decrease fibrinogen and factors V & Decrease fibrinogen and factors V & VIII; VIII;

Bacterial protein - hypersensitivity. Bacterial protein - hypersensitivity.

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Rx usesRx uses: short term emergency treatment before : short term emergency treatment before infarction of tissues ensues:infarction of tissues ensues:

coronary thromboses in MI,coronary thromboses in MI, deep venous thromboses,deep venous thromboses, pulmonary embolism & pulmonary embolism & ischemic stroke (tPA).ischemic stroke (tPA).

Adverse effectsAdverse effects: bleeding, intracerebral : bleeding, intracerebral hemorrhage. hemorrhage.

Reversal: aminocaproic & tranexamic acids. Reversal: aminocaproic & tranexamic acids.

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CAUSES OF BLEEDING

Genetic diseases such as hemophiliaGenetic diseases such as hemophilia Use of thrombolyticsUse of thrombolytics Use of anticoagulantsUse of anticoagulants

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DRUGS USED TO TREAT BLEEDING Infusion of factors VIII and IX Infusion of factors VIII and IX made by recombinant made by recombinant

DNA technology or from human blood serum to treat DNA technology or from human blood serum to treat hemophiliahemophilia

Aminocaproic acid and tranexamic acidAminocaproic acid and tranexamic acid: to reverse : to reverse bleeding caused by use of thrombolytics. Act by inhibiting bleeding caused by use of thrombolytics. Act by inhibiting plasminogen activationplasminogen activation

Protamine sulfateProtamine sulfate: reverse bleeding caused by heparin. : reverse bleeding caused by heparin. Acts by binding ionically to heparin forming an ion Acts by binding ionically to heparin forming an ion complex complex

Vitamin KVitamin K: reverse bleeding caused by warfarin use. : reverse bleeding caused by warfarin use. Though fresh-frozen plasma is used if immediate Though fresh-frozen plasma is used if immediate hemostasis is requiredhemostasis is required..

Blood transfusionBlood transfusion 39

ANEMIA

Is defined as a Is defined as a ↓ in Hb concentration ↓ in Hb concentration resulting from a ↓ in number of circulating resulting from a ↓ in number of circulating RBCs.RBCs.

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CAUSES OF ANEMIA

Chronic blood lossChronic blood loss Bone marrow abnormalitiesBone marrow abnormalities Increased hemolysisIncreased hemolysis MalignanciesMalignancies Renal diseaseRenal disease Drugs: anticancer agentsDrugs: anticancer agents Nutritional deficiency: in iron, folic acid and Nutritional deficiency: in iron, folic acid and

vitamin B12.vitamin B12.41

AGENTS USED TO TREAT ANEMIA IronIron Folic acidFolic acid Vitamin B12Vitamin B12 Erythropoietin: Erythropoietin: made by recombinant DNA made by recombinant DNA

technology used in those pts with renal technology used in those pts with renal failurefailure

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AGENT USED TO TREAT SICKLE CELL DISEASE HydroxyureaHydroxyurea: an anticancer drug : an anticancer drug MOA: MOA: ↑ fetal Hb levels↑ fetal Hb levels ↑ ↑ nitric oxide level in blood → in nitric oxide level in blood → in

vasodilation → ↓ in sicklingvasodilation → ↓ in sickling

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