Flashcards in Antithrombotic and hemostatic drugs Deck (35):
1
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
2
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
3
What property in addition to anticoagulation is notable in heparin?
anti-inflammatory
4
Describe the pharmacology of unfractionated heparin
- unpredictable kinetics, monitor with aPTT
- can inhibit Xa and IIa
- side effects: bleeding, HIT, osteoporosis
- neutralized by protamin
5
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
6
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
7
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
8
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
9
Warfarin is monitored using the
PT/INR, goal is 2.0-3.0
10
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
11
What can be given to reverse a warfarin overdose?
Vitamin K
12
Warfarin should never be given to __________
pregnant women
can cross placenta
13
_________ is a complication of warfarin thought to be due to suppression of protein C
warfarin induced skin necrosis
14
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
15
List drugs that decrease warfarin effects
- drugs that stimulate warfarin metabolism: barbiturates, rifampin, chronic EtOH
16
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
17
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
18
Describe the mechanism of action of aspirin
inhibits platelet activation by irreversibly inhibiting COX-1 which prevents conversion of arachidonic acid to TXA2
19
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
20
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
21
List side effects of aspririn
GI or cerebral bleed, rash, tinnitis
22
What is the mechanism of action of clopidogrel
inhibits ADP-dependent platelet aggregation by binding to the ADP receptor
23
20-30% of people have a CYP2C polymorphism that results in lower production of the active metabolite of _____, resulting in non-response
clopidogrel
24
List indications of clopidogrel
TIA- may be superior to aspirin
Acute coronary syndrome
Prevention of coronary stent occlusion
25
List major side effects of clopidogrel
immune mediated thrombocytopenia, neutropenia
hemorrhage
drug interactions
26
List two drug names that are LMWH
enoxaparin, dalteparin
27
What is the mechanism of action of abciximab?
inhibits platelet aggregation by inhibiting binding of fibrinogen and vWF.
monoclonal antibody against GpIIb/IIIa
28
List indications for abciximab
adjunct therapy to percutaneous coronary intervention
useful in unstable angina if not responding to conventional therapy
29
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
30
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
31
List some indications for fibrinolysis (reteplase and alteplase)
acute MI
acute peripheral arterial obstruction
ischemic stroke
massive PE with hemodynamic compromise
massive proximal DVT
32
List factors that determine the success of thrombolytic therapy
time to administration
character of the thrombus
re-occlusion
33
List three indications for DDAVP
A hemostatic drug used in type I vWF, mild hemophilia, and thrombocytopenia
34
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
35