Salicylates

Aspirin:

Aspirin's long use and availability without prescription diminishes its glamour compared with that of the newer NSAIDs. Aspirin is now rarely used as an anti-inflammatory medication and will be reviewed only in terms of its anti platelets effect (ie, doses of 81–325 mg once daily).

Pharmacokinetics:

Salicylic acid is a simple organic acid with a pKa of 3.0. Aspirin (acetylsalicylic acid; ASA) has a pKa of 3.5. The salicylates are rapidly absorbed from the stomach and upper small intestine yielding a peak plasma salicylate level within 1–2 hours. Aspirin is absorbed as such and is rapidly hydrolyzed (serum half-life 15 minutes) to acetic acid and salicylate by esterases in tissue and blood. Salicylate is nonlinearly bound to albumin. Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates.

Mechanisms of Action:

Aspirin irreversibly inhibits platelet COX so that aspirin's antiplatelet effect lasts 8–10 days (the life of the platelet). In other tissues, synthesis of new COX replaces the inactivated enzyme so that ordinary doses have a duration of action of 6–12 hours.

Clinical Uses:

Aspirin decreases the incidence of transient ischemic attacks, unstable angina, coronary artery thrombosis with myocardial infarction, and thrombosis after coronary artery bypass grafting.

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 effects.

Adverse Effects:

In addition to the common side effects listed above, aspirin's main adverse effects at antithrombotic doses are gastric upset (intolerance) and gastric and duodenal ulcers. Hepatotoxicity, asthma, rashes, gastrointestinal bleeding, and renal toxicity rarely if ever occur at antithrombotic doses.

The antiplatelet action of aspirin contraindicates its use by patients with hemophilia. Although previously not recommended during pregnancy, aspirin may be valuable in treating preeclampsia-eclampsia.

Nonacetylated Salicylates:

These drugs include magnesium choline salicylate, sodium salicylate, and salicyl salicylate. All nonacetylated salicylates are effective anti-inflammatory drugs, although they may be less effective analgesics than aspirin. Because they are much less effective than aspirin as COX inhibitors and they do not inhibit platelet aggregation, they may be preferable when COX inhibition is undesirable such as in patients with asthma, those with bleeding tendencies, and even (under close supervision) those with renal dysfunction.

The nonacetylated salicylates are administered in doses up to 3–4 g of salicylate a day and can be monitored using serum salicylate measurements.

Posted in: Anti inflamatory drugs