Aspirin has anti-inflammatory effects via inhibition of cyclooxygenases (in common with other non-steroidal anti-inflammatory agents), the enzymes which produce prostaglandins. An overdose of aspirin brings about several changes in the body which are unrelated to this mechanism and only occur if high enough doses are imbibed. Salicyclic acid (the active metabolite of aspirin) has multiple effects on metabolic pathways when taken at high doses which lead to a mixture of respiratory alkalosis and metabolic acidosis, depending on the dose, time of presentation after ingestion and differences in metabolism of the drug from person to person.

Unlike paracetamol – the other analgesic commonly presenting as an overdose – aspirin nearly always has early effects on the body such as vomiting, vertigo, tinnitus, fever and sweating.

The initial response to salicylate poisoning is hyperventilation due to direct stimulation of the respiratory centre in the medulla. This inevitably leads to hypocapnia and respiratory alkalosis, which may dominate other metabolic changes that subsequently occur. The kidneys begin to dump HCO3- as a consequence of the respiratory alkalaemia.

The second phase of salicylate overdose is related to the inhibitory effect that this molecule has on several key enzymes of the Krebs cycle. The resultant uncoupling of oxidative phosphorylation leaves the body relying on anaerobic energy, leading to a metabolic acidosis much like you would see in diabetic hypoglycaemia. This process does not replace the initial respiratory alkalosis – the two disturbances co-exist to varying extents.

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