Aspirin: Aspirin is Acetylsalicylic acid which conves to salicylic acid in body ACTIONS 1.Analgesic, antipyretic, anti-inflammatory actions: Aspirin is a weaker analgesic than morphine-type drugs. Aspirin 600 mg < Codeine 60 mg < 6 mg Morphine it effectively relieves inflammation, tissue injury, connective tissue, and integumental pain, but is relatively ineffective in severe visceral and ischaemic pain. The analgesic action is mainly due to obtunding of peripheral pain receptors and prevention of PG-mediated sensitization of nerve endings. No sedation, subjective effects, tolerance or physical dependence is produced. Aspirin resets the hypothalamic thermostat and rapidly reduces fever by promoting heat loss, but does not decrease heat production. Anti-inflammatory action is exeed at high doses (3-6 g/ day or 100 mg/kg/ day) 2. Metabolic effects: significant only at anti-inflammatory doses Cellular metabolism is increased, especially in skeletal muscles, due to uncoupling of oxidative phosphorylation leads to increased heat production. There is increased utilization of glucose leads to blood sugar may decrease (especially in diabetics) and liver glycogen is depleted. Chronic use of large doses cause negative N2 balance by increased conversion of protein to carbohydrate. Plasma free fatty acid and cholesterol levels are reduced. 3.Respiration: Effects are dose-dependent. At antiinflammatory doses, respiration is stimulated by peripheral (increased C02 production) and central (increased sensitivity of respiratory center to C02) actions. Hyperventilation is prominent in salicylate poisoning. The fuher rise in salicylate level causes respiratory depression; death is due to respiratory failure. 4. Acid-base and electrolyte balance: Antiinflammatory doses produce significant changes in the acid-base and electrolyte composition of body fluids. Initially, respiratory stimulation predominates and tends to wash out C02 despite increased production ....respiratory alkalosis, which is compensated by increased renal excretion of HCO3; (with accompanying Na+, K+, and water). Still higher doses cause respiratory depression with C02 retention, while excess C02 production continues.... respiratory acidosis. 5.CVS: Aspirin has no direct effect in therapeutic doses. Larger doses increase cardiac output to meet increased peripheral O2 demand and cause direct vasodilatation. Toxic doses depress vasomotor center: BP may fall. Because of increased cardiac work as well as Na+ and water retention, CHF may be precipitated in patients with low cardiac reserve. 6.GIT: Aspirin and released salicylic acid irritate gastric mucosa, cause epigastric distress, nausea, and vomiting. It also stimulates CTZ. 7.Urate excretion: Aspirin in high dose reduces renal tubular excretion of urate 8. Blood: Aspirin, even in small doses, irreversibly inhibits TXA2 synthesis by platelets. Thus, it interferes with platelet aggregation and bleeding time is prolonged to nearly twice the normal value. long-term intake of large dose decreases synthesis of clotting factors in liver and predisposes to bleeding; can be prevented by prophylactic vit K therapy. ESSENTIALS OF MEDICAL PHARMACOLOGY;7TH EDITION;KD TRIPATHI;PAGE NO195