Drugs used in coagulation disorders

Question 1

Heparins

Answer 1

• Indirect anticoagulants
• Unfractionated heparin, LMWH
• complexes with ATIII
• irreversibly inactivates coag factors IIa, IXa, Xa, XIa, XIIa
• venous thrombosis, PE, MI, unstable angina, adjuvant to PCI & thrombolytics
• parenteral
• monitor bleeding with aPTT
• protamine is reversal agent
• tox: HIT, osteoporosis with chronic use
• LMWH - less adverse effects, more reliable kinetics with renal elimination, protamine reversal less effective
• Fondaparinux
• similar to LMWH

Question 2

Rivaroxaban

Answer 2

• Direct FX inhibitor
• MOA
• inhibits enzymatic action of Xa
• Clinical
• venous thrombosis, PE, stroke prevention in pts with nonvalvular AF
• Kinetics
• oral, no routine monitoring
• Tox
• bleeding
• no reversal agent

Question 3

Dabigatran

Answer 3

• Direct thrombin inhibitor
• MOA
• inhibits enzymatic action of thrombin
• Clinical
• anticoagulation in pts with HIT
• Kinetics
• oral
• Monitor bleeding with aPTT

Question 4

Warfarin

Answer 4

• Coumadin derivate
• MOA
• inhibits vit K epoxide reductase
• Clinical
• venous thrombosis, PE, prevention of thromboembolic complications of AF or cardiac valve replacement
• Kinetics
• oral
• delayed onset and offset
• many interactions
• Tox
• monitor bleeding with PT
• vit K₁ is reversal agent
• thrombosis early in therapy due to protein C deficiency
• teratogen!

Question 5

Alteplase

Answer 5

• Human recombinant t-PA
• MOA
• converts plasminogen to plasmin, whcih degrades fibrin in thrombi
• Clinical
• coronary thrombosis, ischemic stroke, PE
• Kinetics
• parenteral
• Tox
• bleeding, especially cerebral

Question 6

Streptokinase

Answer 6

• Bacterial protein that forms complex with plasminogen, then same mechanism as t-PA
• subject to inactivating antibodies and allergic reactions

Question 7

Antiplatelet drugs (yes it’s all in one big card, good luck)

Answer 7

• Aspirin
• blabla COX inhibitor blabla reduces thromboxane A₂
• prevention & treatment of arterial thrombosis
• lower dose than for anti-inflammatory effects
• irreversible action - longer than pharmacokinetic t_1/2
• Abciximab, eptifibatid
• inhibits platelet aggregation by interfering with GPIIb/IIIa binding to fibrinogen
• during PCI to prevent restenosis
• ACS
• parenteral
• bleeding, thrombocytopenia with prolonged use
• Clopidogrel, ticlopidine
• prodrug - active metabolite irreversibly inhibits platelet ADP receptor
• ACS, prevention of restenosis after PCI, prevention & treatment of arterial thrombosis
• oral
• Dipyridamole, cilostazol
• inhibits adenosine uptake and inhibit phosphodiesterase that degrade cAMP, cGMP
• prevention of thromboembolic complications of cardiac valve replacement
• combined with aspirin for secondary prevention of ischemic stroke

Question 8

Vitamin K₁

Answer 8

• Used as reversal agent in warfarin toxicity or in vit K deficiency
• Oral or parenteral

Question 9

Tranexamic acid (not test material, but clinically used frequently)

Answer 9

• Analog of aminocaproic acid
• MOA
• competitively inhibits plasminogen activation
• Clinical
• excessive fibrinolysis
• Kinetics
• oral, parenteral
• Tox
• thrombosis, hypotension, myopathy, diarrhea