Figure 4.
Aspirin is a weak organic acid, with a pKa of 3.5. Taken orally, it is absorbed in the stomach and the upper small intestine, mainly in the non-ionized form due to the acidic conditions in the stomach. Once absorbed, it is metabolized to acetic acid and salicylate by esterases in tissue and blood (see Figure 4). The free salicylate is then excreted unchanged, or converted to other water-soluble compounds that are then excreted by the kidney.
The excretion of salicylate occurs with first-order kinetics with a half-life between 2 and 19 hours, depending on the dose of aspirin administered.
Aspirin acts by inhibiting the enzyme cyclo-oxygenase (COX), resulting in the inhibition of prostaglandins, which is mainly responsible for its therapuetic effects. Aspirin irreversibly blocks COX unlike other NSAIDs, which are reversible competitive inhibitors. Aspirin acylates a serine residue of the constitutive form of the enzyme. Steric hindrance then prevents access of the substrate to the oxygenase active site.
Aspirin inhibits prostaglandins, which produce vasodilation and increased vascular permeability. This has the effect of reducing pain, stiffness and swelling caused by inflammation.
Aspirin alleviates pain of varying causes, and is most effective for pain of mild to moderate intensity. The analgesic action is associated with the anti-inflammatory action (see above). The drug mainly acts periphally, by inhibiting prostaglandins. These do not themselves cause pain, but thry potentiate pain caused by other mediators of inflammation.
Aspirin reduces elevated temperatures experienced during fever. This reduction in temperature is due to vasodilation of superficial blood vessels which causes increased heat dissipation.
Aspirin also irreversibly inhibits platelet aggregation.
