Anticoagulants/ antiplatelets

Question 1

Arterial clots

Answer 1

platelet rich

Question 2

Venous clots

Answer 2

rich in fibrin

Question 3

Heparin (unfractionated)

Answer 3

complexes and activates antithrombin to increase speed 1000x faster to inactive IIa and Xa; also directly inactivates factor IIa

Question 4

Heparin problem

Answer 4

zero order elimination (frequent APTT testing), hemorrhage (treated with protamine sulfate) and heparin-induced thrombocytopenia (type 2 = generate antibody against heparin-platelet Factor 4, resulting immune complex activates platelets (use argatroban, a thrombin inhibitor)

Question 5

Argatroban

Answer 5

directly inhibit thrombin

Question 6

Low molecular weight heparin (fractionizated)

Answer 6

will not bind to thrombin unlike unfractionated heparin, lower risk of developing type 2 thrombocytopenia, undergoes 1st order elimination (no frequent monitoring)

Question 7

Warfarin

Answer 7

inhibits vitamin K epoxide reductase to inhibit production of clotting factors 2, 7, 9 ,10 by the liver; delay time to act, 8-10 hours (in blood already)

Question 8

Warfarin potential problems

Answer 8

crosses placenta (teratogenic), hemorrhage (treat with vitamin K), interaction with other drugs, Cyp2C9, variability in pharmacodynamics and pharmacokinetics

Question 9

Aspirin

Answer 9

inhibits platelet cyclooxygenase 1 and 2 (thus thromboxane A2); at low does daily aspirin decreases risk of myocardial infarction and ischemic stroke but increase risk of hemorrhagic stroke; increased bleeding time

Question 10

Clopidogrel (given orally)

Answer 10

developed for people who can not tolerate aspirin; a prodrug for which the active metabolite covalently binds to and inactivates the ADP receptor, thereby inhibits the expression of the GP 2b/3a on the platelet surface; affected by Cyp2C19 variant

Question 11

Vorapaxar

Answer 11

binds to PAR1 and prevents its activation by thrombin

Question 12

Dipyridamole

Answer 12

elevates cAMP by inhibiting platelet phosphodiesterase (high cAMP lowers free calcium -> inhibits platelet activation and granule release), and by increasing prostacyclin release from endothelial cells (dilate vessels); used in patients with synthetic material implanted, used in combination with warfarin and heparin

Question 13

Tirofiban (i.v.)

Answer 13

only used in hospital setting during angioplasty or stenting; binds to the GP 2b/3a receptor, blocking cross-linking of platelets/aggregation

Question 14

Streptokinase

Answer 14

i.v.; bind to plasminogen, the resulting complex causes activation of other plasminogen molecules to plasmin

Question 15

Alteplase (tPA)

Answer 15

i.v.; binds directly and catalyzes conversion from plasminogen to plasmin

Question 16

Aminocaproic acid (antidote)

Answer 16

treats hyperfibrinolysis; binds to plasminogen, blocks activation of plasminogen and the interaction of plasmin with fibrin and fibrinogen

Question 17

Heparin reversal agent (antidote)

Answer 17

protamine sulfate

Question 18

Warfarin reversal agent (antidote)

Answer 18

Vitamin K, fresh frozen plasma

Question 19

Anticoagulants have anti platelet activity

Answer 19

Thrombin -> PAR1 -> txA2 and hemostasis/ thrombosis