Drugs for thrombogenesis

Question 1

What are four anticoagulants?

Answer 1

(1) Heparin
(2) Argatroban
(3) Low molecular weight heparin
(4) Warfarin

Question 2

How is heparin administered?

Answer 2

IV because it is highly water soluble and isn’t absorbed

Question 3

What is the molecular structure of heparin?

Answer 3

A long chain of (1) sulfated d-glucuronic acid and d-glucosamine

Question 4

What is the mechanism of action of heparin?

Answer 4

(1) Heparin binds antithrombin III to (2) form antithrombin III-heparin complex, which (3) inactivates Factors IX, X, XI, XII, and XII
(4) Heparin also directly inactivates thrombin

Question 5

What are potential problems with heparin?

Answer 5

(1) Zero order elimination, which makes dose-response relationship hard to control
(2) Hemorrhage
(3) Heparin-induced thrombocytopenia due to formation of heparin-PF4 complex with autoantibodies

Question 6

How does argatroban work?

Answer 6

Thrombin inhibition - alternative to heparin, treat type 2 heparin induced thrombocytopenia

Question 7

How is hemorrhage from heparin treated?

Answer 7

Protamine sulfate as antidote

Question 8

What is the mechanism of action of low molecular weight heparin?

Answer 8

(1) Low molecular weight heparin binds antithrombin III (2) but not thrombin, (3) with lower risk of heparin-induced thrombocytopenia

Question 9

What is the major advantage of low molecular weight heparin over heparin?

Answer 9

First order elimination as opposed to zero order elimination

Question 10

What is the mechanism of action of warfarin?

Answer 10

(1) Warfarin inhibits Vitamin K epoxide reductase, which (2) reduces vitamin K epoxide, (3) allowing activation of Factors II, VII, IX, and X
End result is inhibition of vitamin K-dependent coagulation factors

Question 11

What are potential problems with warfarin?

Answer 11

(1) Hemorrhage
(2) Interactions with other drugs due to Cyp2c9 metabolism
(3) Difficult dosing due to variation in activity of epoxide reductase in the population

Question 12

What is the mechanism of action of aspirin?

Answer 12

(1) Inhibition of cyclooxygenase 1 (COX1), which (2) prevents formation of thromboxane A2 (TXA2)

Question 13

What is the mechanism of action of clopidogrel?

Answer 13

(1) Clopidogrel is a prodrug that is metabolically activated to a product that (2) inactivates ADP receptor, (3) inhibiting activation of GPIIb/IIIa receptor and (4) prevents platelet aggregation

Question 14

What is a potential problem with clopidogrel?

Answer 14

Some people have a Cyp2c19 variant, making them hyporesponsive to clopidogrel due to lack of metabolic activation

Question 15

What is the mechanism of action of vorapaxar?

Answer 15

Binds to protease-activated receptor 1 (PAR1), preventing activation by thrombin

Question 16

What is the mechanism of action of dipyramidole?

Answer 16

(1) Elevation of cAMP by (2) inhibiting phosphodiesterase, (3) lowering free calcium, which (4) inhibits events leading to platelet activation and granule release

Question 17

To whom is dipyramidole administered?

Answer 17

Patients with artificial implants because they tend to cause clot formation

Question 18

What is the mechanism of action of tirofiban?

Answer 18

(1) Binding to GPIIb/IIIa receptor, (2) blocking platelet cross-linking

Question 19

How do anticoagulants work?

Answer 19

Inhibiting thrombin production

Question 20

What are two thrombolytics and how do they work?

Answer 20

(1) Streptokinase and (2) alteplase/tPA

(3) Activation of plasminogen to plasmin, which dissolves fibrin and fibrinogen

Question 21

What is an antidote to streptokinase and alteplase?

Answer 21

(1) Aminocaproic acid, which (2) blocks activation of plasminogen

Question 22

What is an antidote to warfarin?

Answer 22

Vitamin K, prevents hemorrhage