Antithrombotic and hemostatic drugs Flashcards
Define/ describe the three main classes of antithrombotic drugs
- anticoagulants: used to treat or prevent venous thrombosis
- antiplatelets: used to prevent arterial thrombosis
- thromboyltic agents: used to acutely reverse thrombosis
What is the mechanism of the anticoagulant effect of heparin?
accelerates inhibition of coagulation proteases Xa and IIa (thrombin) by antithrombin
heparin binds to antithrombin and induces a conformational change that accelerates the rate of protease inhibition
What property in addition to anticoagulation is notable in heparin?
anti-inflammatory
Describe the pharmacology of unfractionated heparin
- unpredictable kinetics, monitor with aPTT
- can inhibit Xa and IIa
- side effects: bleeding, HIT, osteoporosis
- neutralized by protamin
Describe the pharmacology of low molecular weight heparin
- effects on Xa> IIa (thrombin)
- does not reliably prolong aPTT
- cleared mainly by kidneys
- only partially neutralized by protamine
- no need for routine monitoring and fewer complications
Describe the pharmacology of fondaparinux
- specifically inhibits Xa
- longer half life
- does not require monitoring
- eliminated by kidneys
- can be used in HIT
- not neutralized by protamine
List indications for use of heparins
- LMWH is DOC for DVT/PE, can transition to warfarin
- prevention of post-op thrombosis and during acute MI
- UFH in dialysis and cardiopulmonary bypass machines
_LMWH is DOC in pregnancy
Describe the mechanism of action of warfarin
Warfarin acts by interfering with the vitamin K-dependent gamma carboxylation of glutamines within
the amino-terminus “Gla domain” of the coagulation proteases
Interferes with reduction of vitamin K and depletes the body of this vitamin
Warfarin is monitored using the
PT/INR, goal is 2.0-3.0
List indications for warfarin
- prevent recurrence of VTE, give for 3-6 months after an event
- reduce risk of stroke and arterial emboli in atrial fibrillation or artificial valves
What can be given to reverse a warfarin overdose?
Vitamin K
Warfarin should never be given to __________
pregnant women
can cross placenta
_________ is a complication of warfarin thought to be due to suppression of protein C
warfarin induced skin necrosis
List some drugs that potentiate the effects of warfarin
- inhibitors of warfarin metabolism: phenytoin, metronidazole, chloramphenicol, cimetidine, disulfiram, acute EtOH
- displacement of warfarin from albumin: aspirin, clofibrate
- inhibition of platelet aggregation: aspirin, clobidogrel
- decreased vitamin K synthesis: antibiotics
List drugs that decrease warfarin effects
- drugs that stimulate warfarin metabolism: barbiturates, rifampin, chronic EtOH