Antithrombotic and hemostatic drugs

Question 1

Define/ describe the three main classes of antithrombotic drugs

Answer 1

• anticoagulants: used to treat or prevent venous thrombosis
• antiplatelets: used to prevent arterial thrombosis
• thromboyltic agents: used to acutely reverse thrombosis

Question 2

What is the mechanism of the anticoagulant effect of heparin?

Answer 2

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

Question 3

What property in addition to anticoagulation is notable in heparin?

Answer 3

anti-inflammatory

Question 4

Describe the pharmacology of unfractionated heparin

Answer 4

• unpredictable kinetics, monitor with aPTT
• can inhibit Xa and IIa
• side effects: bleeding, HIT, osteoporosis
• neutralized by protamin

Question 5

Describe the pharmacology of low molecular weight heparin

Answer 5

• 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

Question 6

Describe the pharmacology of fondaparinux

Answer 6

• specifically inhibits Xa
• longer half life
• does not require monitoring
• eliminated by kidneys
• can be used in HIT
• not neutralized by protamine

Question 7

List indications for use of heparins

Answer 7

• 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

Question 8

Describe the mechanism of action of warfarin

Answer 8

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

Question 9

Warfarin is monitored using the

Answer 9

PT/INR, goal is 2.0-3.0

Question 10

List indications for warfarin

Answer 10

• 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

Question 11

What can be given to reverse a warfarin overdose?

Answer 11

Vitamin K

Question 12

Warfarin should never be given to __________

Answer 12

pregnant women

can cross placenta

Question 13

_________ is a complication of warfarin thought to be due to suppression of protein C

Answer 13

warfarin induced skin necrosis

Question 14

List some drugs that potentiate the effects of warfarin

Answer 14

• 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

Question 15

List drugs that decrease warfarin effects

Answer 15

• drugs that stimulate warfarin metabolism: barbiturates, rifampin, chronic EtOH

Question 16

List and describe three direct thrombin inhibitors

Answer 16

• 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

Question 17

List a drug that is a direct factor Xa inhibitor

Answer 17

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

Question 18

Describe the mechanism of action of aspirin

Answer 18

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

Question 19

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

Answer 19

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

Question 20

List indications for aspirin use

Answer 20

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

Question 21

List side effects of aspririn

Answer 21

GI or cerebral bleed, rash, tinnitis

Question 22

What is the mechanism of action of clopidogrel

Answer 22

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

Question 23

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

Answer 23

clopidogrel

Question 24

List indications of clopidogrel

Answer 24

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

Question 25

List major side effects of clopidogrel

Answer 25

immune mediated thrombocytopenia, neutropenia hemorrhage drug interactions

Question 26

List two drug names that are LMWH

Answer 26

enoxaparin, dalteparin

Question 27

What is the mechanism of action of abciximab?

Answer 27

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

Question 28

List indications for abciximab

Answer 28

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

Question 29

What is the mechanism of action of eptifibatide and tirofiban?

Answer 29

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

Question 30

What is the mechanism of action of reteplase and alteplase?

Answer 30

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

Question 31

List some indications for fibrinolysis (reteplase and alteplase)

Answer 31

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

Question 32

List factors that determine the success of thrombolytic therapy

Answer 32

time to administration character of the thrombus re-occlusion

Question 33

List three indications for DDAVP

Answer 33

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

Question 34

List indications for amicar

Answer 34

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

Question 35

What are indications for recombinant factor VIIa?

Answer 35

hemophilia if inhibitors have developed against replacement coagulation factors uncontrolled hemorrhage