34 drugs-used-in-coagulation-and-bleeding-disorders

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

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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

Serotonin (5 HT)

• 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

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Coagulation system is then activated resulting in thrombin generation andfibrin clot formation

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 COAGULATION

AND BLEEDING DISORDERS

BLOOD COAGULATIONCASCADE

Fibrinolysis

• Process of fibrin digestion by the fibrin-specific protease, plasmin

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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

• 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

• Anticoagulants and thrombolytic drugs

• Antiplatelet drugs

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

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

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

DISORDERS

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Thromboxane

Serotonin (5 HT)

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Tissue factor (TF)

Fibrinolysis

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● Ischemic stroke

ANTICOAGULANTS

• Classification

● Given IV

●Warfarin

● Orally active

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

• Highly acidic

• Neutralized by basic molecules (e.g., protamine)

• Given parenterally

● IV or subcutaneously

• Intramuscular injection is avoided

● Risk of hematoma formation

ANTICOAGULANTS

• 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

ANTICOAGULANTS

• Chemistry

Fondaparinux

• Small synthetic drug

• Contains the key pentasaccharide present in unfractionated and LMW heparins

• Administered subcutaneously once daily

ANTICOAGULANTS

• Chemistry

Danaparoid

• LMW heparinoid containing heparan, dermatan and chondroitin sulfates

• Chemically distinct from heparin (no cross-hypersensitivity)

• Can be given intravenously or subcutaneously

ANTICOAGULANTS

• 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

ANTICOAGULANTS

• Provides anticoagulation immediately after administration

• Monitored with the activated partial thromboplastin time (aPTT) or partialthromboplastin time (PTT) laboratory test

ANTICOAGULANTS

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)

ANTICOAGULANTS

• 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

ANTICOAGULANTS

• Clinical use

Heparin

• Used when anticoagulation is need immediately (e.g., when starting therapy)

• Common uses

● DVT

● Pulmonary embolism

● Acute myocardial infarction

ANTICOAGULANTS

• Clinical use

Heparin

• Combined with thrombolytics for revascularization

• Combined with glycoprotein IIB/IIIa inhibitors during angioplasty andplacement of coronary stents

ANTICOAGULANTS

• Clinical use

Heparin

• Does not cross the placental barrier

● Drug of choice in pregnancy

• LMW heparins and fondaparinux

● Similar clinical applications

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ANTICOAGULANTS

• 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

ANTICOAGULANTS

• 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

ANTICOAGULANTS

• 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

ANTICOAGULANTS

• Toxicity

• LMW heparins, fondaparinux and danaparoid

● Less likely to cause this immune-mediatedthrombocytopenia

• Prolonged use of regular heparin is associated withosteoporosis and spontaneous fractures

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

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Chemistry

• Highly acidic

ANTICOAGULANTS

• Chemistry

ANTICOAGULANTS

• Chemistry

Fondaparinux

ANTICOAGULANTS

• Chemistry

Danaparoid

ANTICOAGULANTS

• ATIII

ANTICOAGULANTS

• Bind to ATIII

ANTICOAGULANTS

• Clinical use

Heparin

• Common uses

● DVT

ANTICOAGULANTS

• Clinical use

Heparin

ANTICOAGULANTS

• Clinical use

Heparin

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ANTICOAGULANTS

• Toxicity

Increased bleeding

Protamine sulfate

ANTICOAGULANTS

• Toxicity

Protamine sulfate

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Hirudin

• Specific irreversible thrombin inhibitor from leech saliva

• Given IV

• Monitored by aPTT

ANTICOAGULANTS

Lepirudin

• Recombinant form of the leech protein hirudin

• Given IV

• Excreted by the kidneys

● Can accumulate in patients with renal failure

ANTICOAGULANTS

Bivalirudin

• Modified form of hirudin

• Given IV

• Rapid onset and offset of action

• Clearance is 20% renal and the remainder is

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

• Clearance not affected by renal disease

• Dependent on liver function

● Can accumulate in patients with liver disease

• Administered parenterally

ANTICOAGULANTS

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

ANTICOAGULANTS

• Inhibit both soluble thrombin and the thrombin enmeshed within developingclots

ANTICOAGULANTS

• 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

ANTICOAGULANTS

• Toxicity

• Can cause bleeding

• No reversal agents exist

• Prolonged infusion of lepirudin

● Induce formation of antibodies that form a complex and prolong itsaction

ANTICOAGULANTS

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

ANTICOAGULANTS

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

ANTICOAGULANTS

• Coumarin anticoagulants

Warfarin

• Small, lipid-soluble molecules that are readily absorbed after oraladministration

• Cross the placenta

● Potentially dangerous to the fetus

ANTICOAGULANTS

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

ANTICOAGULANTS

Warfarin

• Racemic mixture

● S-warfarin is 4x more potent than the R-warfarin

• Elimination depends on metabolism by CP450 enzymes

ANTICOAGULANTS

Warfarin and other coumarins

• Interfere with the normal posttranslational modification of clotting factors inthe liver

● Process that depends on vitamin K

ANTICOAGULANTS

• Blocks the alpha carboxylation of severalglutamate residues in prothrombin andfactors II, VII, IX, X

• Results in incomplete coagulationmolecules that are biologically inactive

ANTICOAGULANTS

• Half-lives of 8-60 h

● Anticoagulant effect is observed only after sufficient time has passed forthe preformed normal factors to be eliminated

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

Hirudin

• Given IV

ANTICOAGULANTS

Lepirudin

• Given IV

ANTICOAGULANTS

Bivalirudin

• Given IV

metabolic

ANTICOAGULANTS

Argatroban

• Small molecule

ANTICOAGULANTS

Bivalirudin

Argatroban

ANTICOAGULANTS

• Clinical use

Bivalirudin

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Advantages

● Fixed dosing

ANTICOAGULANTS

Ximelagatran

Dabigatran

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

ANTICOAGULANTS

Warfarin

• Racemic mixture

ANTICOAGULANTS

• 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

ANTICOAGULANTS

Vitamin K-dependent factors

• VII

• IX Half-lives of 6, 24, 40,and 60 h in plasma

• X respectively

• II

ANTICOAGULANTS

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

ANTICOAGULANTS

• More rapid reversal can be achieved by transfusion with fresh or frozenplasma that contains

● Normal clotting factors

● Prothrombin complex concentrates

● Recombinant factor VIIa

ANTICOAGULANTS

• Disappearance of excessive effect

● Not correlated with warfarin concentration

● Reestablishment of normal clotting activity

ANTICOAGULANTS

• Clinical use

• Chronic anticoagulation in all of the clinical situations described previouslyfor heparin

• Contraindicated in pregnant women

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

ANTICOAGULANTS

• Toxicity

• Can cross the placenta

● Hemorrhage in the developing fetus

● Abnormal bone formation

• Has a narrow therapeutic window

ANTICOAGULANTS

• Drug interactions

• Cytochrome P450-inducing drugs

Increase warfarin’s clearance

Reduce the anticoagulant effect of a given dose

Barbiturates, carbamazepine, phenytoin, rifampin

ANTICOAGULANTS

• Cytochrome P450 inhibitors

Reduce warfarin’s clearance

Increase the anticoagulant effect of a given dose

Amiodarone, SSRI, cimetidine

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

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

ANTIPLATELET DRUGS

A. Classification and prototypes

• Increase bleeding time

COX inhibitors

• Aspirin and other NSAIDs

Inhibitors of phosphodiesterase 3

• Dipyridamole and cilostazol

ANTIPLATELET DRUGS

Antagonists of ADP receptors

• Ticlopidine and clopidogrel

Glycoprotein IIb/IIIa receptor inhibitors

• Abciximab, tirofiban, eptifibatide

ANTIPLATELET DRUGS

● Test used to monitor their effects

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

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTICOAGULANTS

• VII

• X respectively

• II

ANTICOAGULANTS

• Stop the drug

● Phytonadione

● 6-24 h

ANTICOAGULANTS

• Clinical use

ANTICOAGULANTS

• Toxicity

Bleeding

Early in therapy

ANTICOAGULANTS

• Toxicity

ANTICOAGULANTS

Vitamin K, plasma

ANTIPLATELET DRUGS

● Prostacyclin

ANTIPLATELET DRUGS

COX inhibitors

ANTIPLATELET DRUGS

Thromboxane A2

ANTIPLATELET DRUGS

Aspirin

• Irreversible enzyme inhibitor

• Particularly effective

• Inhibition persists until new platelets areformed (several days)

• Other NSAIDs cause less persistentantiplatelet effect (hours)

ANTIPLATELET DRUGS

Ticlopidine and clopidogrel

• Irreversible inhibition of the ADP receptor

• Inhibition of ADP-mediated plateletaggregation

ANTIPLATELET DRUGS

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”)

ANTIPLATELET DRUGS

Tirofiban and eptifibatide

• Reversibly block the glycoprotein IIb/IIIa receptors

ANTIPLATELET DRUGS

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

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

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

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

● Used to treat intermittent claudication

●Manifestation of peripheral arterial disease

ANTIPLATELET DRUGS

A. Toxicity

• Cause GI and CNS effects

All antiplatelet drugs

• Significantly enhance the effects of other anticlotting agents

ANTIPLATELET DRUGS

Ticlopidine

• Bleeding in up to 5% of patients

• Severe neutropenia in about 1%

• Rare thrombotic thrombocytopenic purpura (TTP)

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

Glycoprotein IIb/IIIa receptor blocking drugs

• Bleeding

• Thrombocytopenia (with chronic use)

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

• Classification and Prototypes

Tissue plasminogen activator (t-PA)

• Alteplase, tenecteplase, and reteplase

Anistreplase

Urokinase

Streptokinase

• All are given IV

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

THROMBOLYTIC AGENTS

• 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

THROMBOLYTIC AGENTS

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

THROMBOLYTIC AGENTS

• Streptokinase

• Obtained from bacterial cultures

• Not an enzyme

• Forms a complex with endogenousplasminogen

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

ANTIPLATELET DRUGS

Aspirin

ANTIPLATELET DRUGS

Abciximab

ANTIPLATELET DRUGS

A. Clinical use

Aspirin

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Clinical use

ANTIPLATELET DRUGS

A. Toxicity

ANTIPLATELET DRUGS

Ticlopidine

Clopidogrel

• Less hematoxic

ANTIPLATELET DRUGS

• Toxicity

• Bleeding

• Headaches

• Palpitations

THROMBOLYTIC AGENTS

Anistreplase

Urokinase

Streptokinase

THROMBOLYTIC AGENTS

Plasmin

THROMBOLYTIC AGENTS

• t-PA

Alteplase

Tenecteplase

THROMBOLYTIC AGENTS

Reteplase

• Urokinase

THROMBOLYTIC AGENTS

• Streptokinase

• Not an enzyme

THROMBOLYTIC AGENTS

• 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

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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

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

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

• Most important hazard

• Same frequency with all drugs

Cerebral hemorrhage

• Most serious manifestation

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 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

Treatment

• Vitamin K

• Preformed clotting factors

• Antiplasmin drug

• Platelets for thrombocytopenia

• 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

• 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

• 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

• 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

Aprotinin

• Serin protease inhibitor (serpin)

• Inhibits fibrinolysis by free plasmin

• Associated with increased risk of renal failure, heart attack and stroke

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

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1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

THROMBOLYTIC AGENTS

• Anistreplase

• Prodrug

● Long half-life

Loading...

1 – 2 h

THROMBOLYTIC AGENTS

• Clinical use

THROMBOLYTIC AGENTS

• Toxicity

Bleeding

Cerebral hemorrhage

THROMBOLYTIC AGENTS

• Toxicity

• Human proteins

• May result from

● Hemophilia

Treatment

• Vitamin K

● Fresh plasma

• Orally active

Aprotinin

34 drugs-used-in-coagulation-and-bleeding-disorders

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