Platelet aggregation is blocked by aspirin due to its action on:
Ans. c. Thromboxane A2 (Ref: Goodman Gilman 12/e p868; Katzung 12/e p638; KDT 7/e p195, 6/e p186, 609)Aspirin causes several different effects in the body, mainly the reduction of inflammation, analgesia, the prevention of clotting, and the reduction of fever. Much of this is believed to be due to decreased production of prostaglandins and TXA2."In platelets, the major cyclooxygenase product is TxA2 (thromboxane A 2), a labile inducer of platelet aggregation and a potent vasoconstrictor. Aspirin blocks production of TxA2 by acetylating a serine residue near the active site of platelet cyclooxygenase-1 (COX-1), the enzyme that produces the cyclic endoperoxide precursor of TxA2. Because platelets do not synthesize new proteins, the action of aspirin on platelet COX-1 is permanent, lasting for the life of the platelet (7-10 days). Thus. repeated doses of aspirin produce a cumulative effect on platelet function. "-- Goodman Gilman 12/e p868Drugs affecting Thromboxane A2COX inhibitors like aspirin decreases the synthesis of TXA2QDaltroban & Sultroban are TXA2 receptor antagonistsQDazoxihen inhibits the enzyme thromboxane synthetaseQAspirinAspirin is now rarely used as an anti-inflammatory medication and used for its anti-platelet effectsQ (doses of 81-325 mg once daily).Mechanisms of Action:In platelets, the major cyclooxygenase product is TxA2, a labile inducer of platelet aggregation & a potent vasoconstrictorQ.Aspirin blocks production of TxA2 by acetylating a serine residue near active site of platelet cyclooxygenase-1 (COX-1), enzyme that produces cyclic endoperoxide precursor of TxA2Q.Because platelets do not synthesize new proteins, the action of aspirin on platelet COX-1 is permanent, lasting for the life of the platelet (7-10 days)Q.Clinical UsesAspirin decreases the incidence of transient ischemic attacks, unstable angina, coronary artery thrombosis with myocardial infarction & thrombosis after coronary artery bypass graftingQ.Epidemiologic studies suggest that long-term use of aspirin at low- dosage is associated with a lower Incidence of colon cancer, possibly- related to its COX-Inhibiting effectsQ.Adverse EffectsGastric upset (intolerance) and gastric & duodenal ulcersQ.Hepatotoxicity, asthma, rashes, GI bleeding & renal toxicity rarely if ever occur at antithrombotic doses.Antiplatelet action of aspirin contraindicates its use by patients with hemophiliaQ.
Prostacyclin
PGF 2 alpha
Thromboxane A2
Phospholipase C
Antiplatelets and Fibrinolytics