Aspirin. Major analgesic which is responsible for many cases of therapeutic, accidental and intentional poisoning. Metabolized by hydrolysis to salicylic acid which is conjugated. Conjugation pathways are saturable so that the half-life increases with dosage. Therefore blood level of salicylate rises disproportionately with dosage. When salicylate enters tissues, it uncouples oxidative phosphorylation causing: heat generation, increased cellular metabolism and production of carbon dioxide, increased requirement for oxygen, increased rate and depth of breathing via the effect on central respiratory control. This leads to metabolic alkalosis and overcompensation leads to metabolic acidosis. Acidosis allows more non-ionized salicylate to enter tissues including CNS, leading to more metabolic effects and greater acidosis and decreased urinary excretion. Effects on CNS may lead to death. Treatment involves alkaline diuresis, reduction of temperature, replacement of ions and glucose.
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