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Which of the following drug is a phosphodiesterase inhibitor? (AIIMS Nov 2012)

A Aspirin
B Clopidogrel

C Tirofiban
D None of the above

Ans. B


Antiplatelet drugs

1. Aspirin

Inhibiting platelet cyclooxygenase (COX)-1

2. Thienopyridines

The thienopyridines include ticlopidine, clopidogrel, and prasugrel, drugs that target P2Y12, a key ADP receptor on platelets.

Mechanism of Action

By inhibiting phosphodiesterase

Dipyridamole blocks the breakdown of cAMP. Increased levels of cAMP reduce intracellular calcium and inhibit platelet activation.

Heparin-Induced Thrombocytopenia (HIT) (Hari- 18th – Pg.- 967)

Drug-induced thrombocytopenia due to heparin differs from that seen with other drugs in two major ways.

1. The thrombocytopenia is not usually severe, with nadir counts rarely <20,000/μL.

2. HIT is not associated with bleeding and, in fact, markedly increases the risk of thrombosis. HIT results from antibody formation to a complex of the platelet-specific protein platelet factor 4 (PF4) and heparin. The antiheparin/PF4 antibody can activate platelets through the FcRIIa receptor and also activate monocytes and endothelial cells.

a. HIT can occur after exposure to LMWH as well as unfractionated heparin (UFH), although it is about 10 times more common with the latter.

b. Most patients develop HIT after exposure to heparin for 5–14 days. It occurs before 5 days in those who were exposed to heparin in the prior few weeks or months (<~100 days) and have circulating antiheparin/PF4 antibodies.

c. Rarely, thrombocytopenia and thrombosis begin several days after all heparin has been stopped (termed delayed-onset HIT).

d. The 4 T's have been recommended to be used in a diagnostic algorithm for HIT: thrombocytopenia, timing of platelet count drop, thrombosis and other sequelae such as localized skin reactions, and other causes of thrombocytopenia not evident.

Site of action of various antiplatelet drug (Ref. Hari- 18th ed., Pg.- 989, fig 118.3)

Site of action of antiplatelet drugs.

1. Aspirin inhibits thromboxane A2 (TXA2) synthesis by irreversibly acetylating cyclooxygenase-1 (COX-1). Reduced TXA2 release attenuates platelet activation and recruitment to the site of vascular injury.

2. Ticlopidine, clopidogrel, and prasugrel irreversibly block P2Y12, a key ADP receptor on the platelet surface; cangrelor and ticagrelor are reversible inhibitors of P2Y12.

3. Abciximab, eptifibatide, and tirofiban inhibit the final common pathway of platelet aggregation by blocking fibrinogen and von Willebrand factor binding to activated glycoprotein (GP) IIb/IIIa.

4. Vorapaxar and atopaxar inhibit thrombin-mediated platelet activation by targeting protease-activated receptor-1 (PAR-1), the major thrombin receptor on human platelets. (Recent Advances)