Anticoagulants, Antithrombotics & Thrombolytic Drugs

Question 1

Heparine Sulfate (UFH)

Answer 1

Anticoagulant

• Linear polysaccharide delivered parenterally. Bovine or porcine source.
• Catalyzes antithrombin activity by direct binding. Inhibits IIa, IXa, Xa.
• Used to treat acute DVT or PE, prophylaxis of venous thrombosis and DIC and arterial thrombosis
• Side Effects: bleeding, allergy, thrombosis, osteoporosis, HIT-heparin induced thrombocytopenia- systemic hypercoagulable state following > 7 day treatment of heparin. Never administer intramuscularly
• Monitor PTT
• Clearance by RES (saturatable) and kidney (non-saturatable)

Question 2

Rivaroxaban

Answer 2

Anticoagulant

• Orally admin once daily factor X inhibitor
• Maximal effect 4 h
• Liver, Renal and Fecal biliary clearance
• No monitoring, short half life, no reversal agent

Question 3

Warfarin

Answer 3

Antigoagulant

• Inhibits vitamin K metabolism which disrupts gamma carboxylation of several glutamate residues in factors II, VII, IX, X, C, S. C & S drops first, so does with heparin at first. No degradation of factors. Effect dependent on factor half life.
• Side Effects: bleeding, skin necrosis, teratogenesis
• INTERACTS WITH NUMEROUS OTHER DRUGS, DISEASES, DIETS!
• Liver and kidney clearance
• Monitor therapy with INR and PT
• Add Menadione (Vit K), FFP and factor VIIa to counteract

Question 4

Protamine

Answer 4

Heparin Antagonist

*Cationic protein binds to heparin to form stable ion pair.

Question 5

Menadione

Answer 5

Vitamin K, Warfarin Antidote

Question 6

Dalteparin

Answer 6

LMW Heparin

• Enhances antithrombin action on factor X
• Metabolized by kidney, so use caution in pts with renal disease
• Doesn’t require careful monitoring
• Protamine partially effective inhibitor

Question 7

Enoxaparin

Answer 7

LMW Heparin

• Enhances antithrombin action on factor X
• Metabolized by kidney, so use caution in pts with renal disease
• Doesn’t require careful monitoring
• Protamine partially effective inhibitor

Question 8

Fondaparinux

Answer 8

LMW Heparin

• Pentasaccharide with added methyl groups
• Enhances antithrombin action on factor X
• Metabolized/cleared by kidney, so use caution in pts with renal disease
• Doesn’t require careful monitoring
• Protamine INEFFECTIVE

Question 9

Argatroban

Answer 9

Direct Thrombin Inhibitor

• Small molecule administered IV due to short half life
• Hepatic clearance
• Selection based on clearance organ function

Question 10

Bivalirudin

Answer 10

Direct Thrombin Inhibitor

• 20 aa peptide, admin IV
• Hepatic and Renal (20%) clearance
• Selection based on clearance organ function

Question 11

Lepirudin

Answer 11

Direct Thrombin Inhibitor

• 65 aa peptide, admin IV
• Renal Clearance
• Selection based on clearance organ function

Question 12

Dabigatran

Answer 12

Direct Thrombin Inhibitor

• Oral, effect within 2-3 h
• 80% renal clearance
• No monitoring
• Short half life
• No good reversal agent
• Side Effect: GI Bleeding

Question 13

Tissue Plasminogen Activator (tPA)

Answer 13

Thrombolytic, human

• Shortest half life
• Used to treat MI, PE, or massive Venous thrombosis
• 1% Risk of intracranial hemorrhage

Question 14

Streptokinase

Answer 14

Thrombolytic, bacterial

• Longest half life
• Used to treat MI, PE, or massive Venous thrombosis
• 1% Risk of intracranial hemorrhage

Question 15

Urokinase

Answer 15

Thrombolytic, human

• Intermediate half life
• Used to treat MI, PE, or massive Venous thrombosis
• 1% Risk of intracranial hemorrhage

Question 16

Abciximab

Answer 16

Antiplatelet Drug, Glycoprotein IIb/IIIa Inhibitor

• Monoclonal Ab
• Inhibit platelet IIb/IIIa receptor complex which acts as a receptor for fibrinogen, vitronectin and vWF

Question 17

Aspirin

Answer 17

Antiplatelet Drug
*Inhibits synthesis of thromboxane A2 by irreversible acetylation of COX. Thromboxane A2 causes platelets to aggregate
*Most commonly used anti-platelet drug. Used to prevent TIA, stroke, MI, coronary restenosis following MI/Fibrinolytic Therapy/Bypass Grafting.
Side Effects: Excessive bleeding

Question 18

Clopidogrel

Answer 18

Antiplatelet Drug, Thienopyridine Derivative

• Reduce platelet aggregation by irreversibly blocking P2Y12 receptor on platelets. No effect on PG metabolism.
• Used in pts undergoing coronary stent or pts who can’t tolerate aspirin.
• Fewer side effects than Ticlopidine
• Activated by CYP2C19, genetic test required to determine susceptibility

Question 19

Prasurgel

Answer 19

Antiplatelet Drug, Thienopyridine Derivative

• Reduce platelet aggregation by irreversibly blocking P2Y12 receptor on platelets. No effect on PG metabolism.
• Used in pts who can’t tolerate aspirin.
• Unlike Clopidogrel, metabolized through hydrolysis. Decreases platelet aggregation more rapidly and in more individuals than Clopidogrel

Question 20

Ticlopidine

Answer 20

Antiplatelet Drug, Thienopyridine Derivative

• Reduce platelet aggregation by irreversibly blocking P2Y12 receptor on platelets. No effect on PG metabolism.
• Used in pts undergoing coronary stent or pts who can’t tolerate aspirin.
• Side effects: diarrhea, nausea, dyspepsia, hemorrhage and rarely leukopenia

Question 21

Tirofiban

Answer 21

Antiplatelet Drug, Glycoprotein IIb/IIIa Inhibitor

• Small molecule inhibitor
• Inhibit platelet IIb/IIIa receptor complex which acts as a receptor for fibrinogen, vitronectin and vWF

Question 22

Eptifibatide

Answer 22

Antiplatelet Drug, Glycoprotein IIb/IIIa Inhibitor

• analogue of carboxy terminal of fibrinogen which mediates interactions with receptor
• Inhibit platelet IIb/IIIa receptor complex which acts as a receptor for fibrinogen, vitronectin and vWF