Aspirin
Aspirin and other nonsteroidal anti-inflammatory drugs are weak organic acids. They all inhibit prostaglandin biosynthesis. They decrease the production of free radicals and of superoxide and may interact with adenylyl cyclase to alter the cellular concentration of cAMP. Aspirin is the drug of choice for treating the majority of articular and musculoskeletal disorders. It is also the standard against which all anti-inflammatory agents are compared.
Pharmacokinetics:
The salicylates are rapidly absorbed from the stomach and upper small intestine. The acid medium in the stomach keeps a large fraction of the salicylate in the nonionized form, promoting absorption. However, the drug may damage the mucosal barrier. Aspirin is absorbed as such and is rapidly hydrolyzed to acetic acid and salicylate by esterases in tissue and blood. Salicylate is bound to albumin. Ingested salicylate and that generated by the hydrolysis of aspirin may be excreted unchanged, but most is converted to water-soluble conjugates that are rapidly cleared by the kidney. Alkalinization of the urine increases the rate of excretion of free salicylate.
Pharmacodynamics
Mechanism of Action: Aspirin irreversibly blocks the enzyme cyclooxygenase; the drug decreases the formation of both the prostaglandins and thromboxane A2 but not the leukotrienes.
Anti inflammatory Effects:
In addition to reducing the synthesis of eicosanoid mediators, aspirin also interferes with the chemical mediators of the kallikrein system. Thus, aspirin inhibits granulocyte adherence to damaged vasculature, stabilizes lysosomes, and inhibits the migration of polymorphonuclear leukocytes and macrophages into the site of inflammation.
Analgesic Effects:
Aspirin is most effective in reducing pain of mild to moderate intensity. Muscular, vascular, and dental origin, postpartum states, arthritis, and bursitis are alleviated by aspirin. Aspirin acts peripherally through its effects on inflammation but probably also inhibits pain stimuli at a subcortical site.
Antipyretic Effects:
Aspirin reduces elevated temperature. The fall in temperature is related to increased dissipation of heat caused by vasodilation of superficial blood vessels. The antipyresis may be accompanied by profuse sweating. Aspirin blocks the pyrogen-induced production of prostaglandins and the central nervous system response to interleukin-1.
Platelet Effects:
Aspirin inhibits platelet aggregation by inhibition of thromboxane synthesis. Because its action is irreversible, aspirin inhibits platelet aggregation for up to 8 days (until new platelets are formed).
Clinical Uses
Analgesic, antipyretics, and anti-inflammatory effects: Aspirin is one of the most frequently employed drugs for relieving mild to moderate pain of varied origin. Aspirin is not effective in the treatment of severe visceral pain (acute abdomen, renal colic, pericarditis, or myocardial infarction). It and other NSAIDs have been combined with opioid analgesics for treatment of cancer pain. Used in the treatment of rheumatoid arthritis, rheumatic fever, and other inflammatory joint conditions.
Inhibition of platelet aggregation: Aspirin has been shown to decrease the incidence of transient ischemic attacks and unstable angina in men. It reduces the incidence of thrombosis in coronary artery bypass grafts. It may also reduce the incidence of myocardial infarction.
Adverse Effects
Gastrointestinal Effects: the main adverse effect is gastric upset (intolerance). The gastritis that occurs with aspirin may be due to irritation of the gastric mucosa by the undissolved tablet, to absorption in the stomach of nonionized salicylate, or to inhibition of protective prostaglandins.
Central Nervous System Effects: With higher doses, patients may experience “salicylism” tinnitus, decreased hearing, and vertigo reversible by reducing the dosage. Still larger doses of salicylates cause hyperpnea through a direct effect on the medulla. At toxic levels, respiratory alkalosis may occur as a result of the increased ventilation. Later, acidosis supervenes from accumulation of salicylic acid derivatives and depression of the respiratory center.
Other Adverse Effects: Aspirin in a low daily dose usually increases serum uric acid levels, whereas doses exceeding 4 g daily decrease urate levels below 2.5 mg/dL. Salicylates may cause reversible decrease of glomerular filtration rate in patients with underlying renal disease. Asprin is contraindicated in children with viral upper respiratory tract infections, because it may precipitate Raye syndrome.
Leave a Reply