PARACETAMOL

This causes hepatic damage in overdose and can occasionally cause renal failure. The antidote of choice is i.v. N-acetylcysteine (NAC), which provides complete protection against toxicity if given <10 hrs after overdose (Fig. 4.1). A patient presenting >8 hrs after ingestion should have immediate NAC administration, which can later be stopped if the paracetamol level is below the treatment line. If a patient presents >15 hrs after ingestion, LFTs, PTR (or INR) and renal function tests should be performed, the antidote started, and a poisons information centre or local liver unit contacted for advice. Liver transplantation should be considered in individuals who develop acute liver failure due to paracetamol poisoning. If multiple ingestions of paracetamol have taken place over several hours or days (a staggered overdose), plasma paracetamol concentration will be uninterpretable. Such patients should be given NAC if the paracetamol dose exceeds 150 mg/kg body weight in any one 24-hr period (75 mg/kg in ‘high-risk groups’).

Fig. 4.1 The management of a paracetamol overdose patient.

SALICYLATES (ASPIRIN)

Doses >150, 250 and 500 mg aspirin/kg body weight produce mild, moderate and severe poisoning respectively. Common symptoms are nausea, vomiting, tinnitus and deafness. Direct stimulation of the respiratory centre produces hyperventilation. Signs of serious salicylate poisoning include metabolic acidosis, renal failure and CNS effects such as agitation, confusion, coma and fits. Death can occur as a consequence of CNS depression and cardiovascular collapse. Plasma salicylate concentration is most accurately measured >6 hrs after ingestion because of continued absorption of the drug. Any significant metabolic acidosis should be treated with sufficient i.v. sodium bicarbonate (8.4%) to normalise [H+]. Patients are often very dehydrated, and fluid loss from vomiting and sweating must be replaced. Urinary alkalinisation is indicated for adult patients with salicylate concentrations of 600–800 mg/l. It is critical to check that urine pH has increased to >8. Haemodialysis should be considered if serum salicylate is >800 mg/l; if there is resistant metabolic acidosis; or if there are severe CNS effects (coma, convulsions).

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

Overdose of most NSAIDs usually causes little more than minor GI upset, including mild abdominal pain, vomiting and diarrhoea. However, 10–20% of patients have convulsions; these are usually self-limiting and seldom need treatment other than airway protection and oxygen.

CARDIOTOXIC DRUGS

The main categories are β-blockers, digoxin, calcium channel blockers and TCAs.

In many countries, the more cardiotoxic TCAs are being replaced with the less cardiotoxic SSRIs for the treatment of depression. However, in large doses SSRIs can still cause hypotension and arrhythmias.

QUININE

The average fatal dose in an adult is 8 g, although deaths have been reported with as little as 1.5 g in an adult and 900 mg in a child. Quinine causes retinal vasoconstriction and has a direct toxic effect on retinal photoreceptor cells; it can cause blindness. Other features include nausea, vomiting, tinnitus, deafness, headache and tremor. In large overdoses, ataxia, drowsiness, coma, respiratory depression, haemolysis and cardiac effects can occur (hypotension, arrhythmias). Treatment is with activated charcoal and ventilatory support, as required.