Cardin Mechanism of Action

Pharmacology: Pharmacodynamics: Metabolism of arachidonic acid via the enzyme cyclooxygenase produces mainly thromboxane (TxA₂) in platelets and prostacyclin (PGI₂) in the vascular endothelium. TxA₂ causes vasoconstriction and induces platelet aggregation and PGI₂ causes vasodilation and has a platelet anti-aggregatory effect. Platelet cyclooxygenase is more sensitive to aspirin inhibition and can only be regenerated with the formation of new platelets. Acetylsalicylic acid can therefore have a selective inhibitory effect on thromboxane production and hence on platelet aggregation. In vitro and ex vivo studies have shown that at low doses (100 mg), there is a differential effect between the inhibitory action of aspirin on platelet cyclooxygenase and the cyclooxygenase in the blood vessels. At these doses, there is complete inhibition of platelet aggregation induced by collagen, ADP and arachidonic acid. The anti-inflammatory, antipyretic and analgesic actions of aspirin are also thought to be mediated via inhibition of prostaglandin biosynthesis.
Pharmacokinetics: After oral administration of aspirin-glycine, aspirin is generally well absorbed from the gastrointestinal tract, partly from the stomach and mainly from the small intestine. Time to peak plasma levels is within 15 min.
Salicylate is 80-90% bound to plasma protein especially albumin, at clinical concentrations of salicylate.
Aspirin is converted to salicylic acid (salicylate) in many tissues but primarily in the gastrointestinal mucosa and the liver.
Salicylates are excreted predominantly by the kidneys. Most of the administered dose can be recovered in the urine as free salicylate (10%) or metabolites (75% as salicyluric acid). Excretion of free salicylate is extremely variable, 85% of ingested aspirin in alkaline urine, 5% in acidic urine.
Patients with impaired renal function require dosage adjustment. The plasma elimination half-life for aspirin is approximately 30 min. The half-life of salicylate is therapeutically more important and is dose-dependent, increasing as the plasma concentration increases. At low doses, the elimination half-life is 2-3 hrs and at high doses 13-30 hrs.
Plasma ASA rather than SA is required for antiplatelet effect and this can best be achieved with soluble aspirin and aspirin-glycine formulations where first-pass metabolism in the gastrointestinal tract is minimised.