Antithrombotic and hemostatic drugs Flashcards Preview

Heme > Antithrombotic and hemostatic drugs > Flashcards

Flashcards in Antithrombotic and hemostatic drugs Deck (35):

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?



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


List and describe three direct thrombin inhibitors

- argatroban: monitor by aPTT
- bivalirudin: IV drug cleared by kidneys, used in percutaneous coronary angioplasty and HIT
- dabigatran: oral alternative to warfarin, no routine monitoring and no antidote


List a drug that is a direct factor Xa inhibitor

rivaroxaban: used to prevent VTE in orthopedic surgeries, stroke prevention in atrial fibrillation, tx of VTE


Describe the mechanism of action of aspirin

inhibits platelet activation by irreversibly inhibiting COX-1 which prevents conversion of arachidonic acid to TXA2


How do other NSAIDs that reversibly inhibit COX interact with aspirin?

compete with aspirin for binding to COX1, they can interfere with the anti-platelet effects
of aspirin


List indications for aspirin use

unstable angina
prevention of thrombosis after CABG
Coronary angioplasty
prevention of thrombosis in artificial heart valves
prevention of acute MI
TIA prophylaxis


List side effects of aspririn

GI or cerebral bleed, rash, tinnitis


What is the mechanism of action of clopidogrel

inhibits ADP-dependent platelet aggregation by binding to the ADP receptor


20-30% of people have a CYP2C polymorphism that results in lower production of the active metabolite of _____, resulting in non-response



List indications of clopidogrel

TIA- may be superior to aspirin
Acute coronary syndrome
Prevention of coronary stent occlusion


List major side effects of clopidogrel

immune mediated thrombocytopenia, neutropenia
drug interactions


List two drug names that are LMWH

enoxaparin, dalteparin


What is the mechanism of action of abciximab?

inhibits platelet aggregation by inhibiting binding of fibrinogen and vWF.
monoclonal antibody against GpIIb/IIIa


List indications for abciximab

adjunct therapy to percutaneous coronary intervention
useful in unstable angina if not responding to conventional therapy


What is the mechanism of action of eptifibatide and tirofiban?

Mimic a peptide that is a ligand for GpIIb/IIIa, thus inhibiting fibrinogen binding and preventing aggregation of platelets


What is the mechanism of action of reteplase and alteplase?

tPA recombinant forms, work by converting plasminogen to plasmin so it can digest the fibrin thrombus


List some indications for fibrinolysis (reteplase and alteplase)

acute MI
acute peripheral arterial obstruction
ischemic stroke
massive PE with hemodynamic compromise
massive proximal DVT


List factors that determine the success of thrombolytic therapy

time to administration
character of the thrombus


List three indications for DDAVP

A hemostatic drug used in type I vWF, mild hemophilia, and thrombocytopenia


List indications for amicar

Hemostatic drug that inhibits plasminogen activation
used for post-op bleeding, to reduce bleeding in coronary bypass, to reverse bleeding due to thrombolytic drugs


What are indications for recombinant factor VIIa?

hemophilia if inhibitors have developed against replacement coagulation factors

uncontrolled hemorrhage