Flashcards in Drugs for thrombogenesis Deck (22):
What are four anticoagulants?
(3) Low molecular weight heparin
How is heparin administered?
IV because it is highly water soluble and isn't absorbed
What is the molecular structure of heparin?
A long chain of (1) sulfated d-glucuronic acid and d-glucosamine
What is the mechanism of action of heparin?
(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
What are potential problems with heparin?
(1) Zero order elimination, which makes dose-response relationship hard to control
(3) Heparin-induced thrombocytopenia due to formation of heparin-PF4 complex with autoantibodies
How does argatroban work?
Thrombin inhibition - alternative to heparin, treat type 2 heparin induced thrombocytopenia
How is hemorrhage from heparin treated?
Protamine sulfate as antidote
What is the mechanism of action of low molecular weight heparin?
(1) Low molecular weight heparin binds antithrombin III (2) but not thrombin, (3) with lower risk of heparin-induced thrombocytopenia
What is the major advantage of low molecular weight heparin over heparin?
First order elimination as opposed to zero order elimination
What is the mechanism of action of warfarin?
(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
What are potential problems with warfarin?
(2) Interactions with other drugs due to Cyp2c9 metabolism
(3) Difficult dosing due to variation in activity of epoxide reductase in the population
What is the mechanism of action of aspirin?
(1) Inhibition of cyclooxygenase 1 (COX1), which (2) prevents formation of thromboxane A2 (TXA2)
What is the mechanism of action of clopidogrel?
(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
What is a potential problem with clopidogrel?
Some people have a Cyp2c19 variant, making them hyporesponsive to clopidogrel due to lack of metabolic activation
What is the mechanism of action of vorapaxar?
Binds to protease-activated receptor 1 (PAR1), preventing activation by thrombin
What is the mechanism of action of dipyramidole?
(1) Elevation of cAMP by (2) inhibiting phosphodiesterase, (3) lowering free calcium, which (4) inhibits events leading to platelet activation and granule release
To whom is dipyramidole administered?
Patients with artificial implants because they tend to cause clot formation
What is the mechanism of action of tirofiban?
(1) Binding to GPIIb/IIIa receptor, (2) blocking platelet cross-linking
How do anticoagulants work?
Inhibiting thrombin production
What are two thrombolytics and how do they work?
(1) Streptokinase and (2) alteplase/tPA
(3) Activation of plasminogen to plasmin, which dissolves fibrin and fibrinogen
What is an antidote to streptokinase and alteplase?
(1) Aminocaproic acid, which (2) blocks activation of plasminogen