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Aspirin use as Cardiovascular drug (Anti platelet)
Tuesday, September 27, 2011 Posted by Piscean


Aspirin use as Cardiovascular drug (Anti platelet)

The main antiplatelet effect of aspirin is to irreversibly block the enzyme cyclo-oxygenase-1 (COX-1) and consequently reduce the synthesis of various prostanoids (eg thromboxane A2 prostacyclin). COX-1 catalyses the production of thromboxane A2 by platelets and of prostacyclin by endothelial cells. Thromboxane A2 promotes platelet aggregation and vasoconstriction. Prostacyclin inhibits platelet aggregation and causes vasodilation. The net pharmacological action of aspirin is to reduce thrombosis and prolong bleeding time.

Unlike endothelial cells, platelets cannot regenerate cyclo-oxygenase. Recovery of normal haemostasis after stopping aspirin depends on the production of new, fully-functional platelets from megakaryocytes. However, platelet turnover may be accelerated in acute vascular events, and this would support daily rather than alternate day aspirin intake.

Formulations: It is important to distinguish between the effects of a single dose of aspirin and repeated daily dosing. When given as a single dose, soluble aspirin 300 mg is more than sufficient to maximally inhibit platelet function within 30 minutes. Thus, when an immediate antiplatelet effect is required, such as for acute myocardial infarction, unstable angina or acute ischaemic stroke, a loading dose of 150 to 300 mg of aspirin is recommended, as this dose produces rapid and complete inhibition of thromboxane A2–mediated platelet aggregation. Crushing, sucking or chewing a tablet can give more rapid absorption.
Soluble aspirin at a dose of 40 to 80 mg daily has a cumulative effect, such that it maximally inhibits platelet thromboxane formation (by more than 95%) after 4 to 5 days. Enteric-coated aspirin 80 to 100 mg daily also produces cumulative and near complete inhibition of platelet aggregation and thromboxane formation in 3 to 5 days.
Precautions: Aspirin is contraindicated in patients with a definite history of NSAID hypersensitivity (particularly NSAID-induced asthma) and in active peptic ulcer disease. Benefits need to be weighed against the risk. For further information,. Aspirin should not be used in children under the age of 12 years because of its rare association with Reye's syndrome. Neither surgery nor use of perioperative subcutaneous heparin necessarily contraindicates the use of aspirin in vascular disease, but bleeding will be increased. Continuation involves a risk–benefit evaluation. Spontaneous bleeding has been reported in patients taking ginkgo biloba who are also taking aspirin. Also be wary about the combination of aspirin with other complementary medicines that may have antiplatelet effects.
Adverse effects: Aspirin in doses between 75 mg and 325 mg per day is antithrombotic. Adverse effects such as gastrointestinal or cerebral haemorrhage are dose related. Aspirin in a dose of 75 to 150 mg per day is effective for long-term use, and this dose minimises (but doesn't eliminate) the risk of adverse effects. Aspirin at doses above 300 mg daily does not offer further therapeutic benefit, and increases the risk of clinically significant adverse effects.

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