Overdose : מינון יתר

4.9 Overdose
Paracetamol
Paracetamol overdose may cause liver failure which may require liver transplant or lead to death. Liver damage is possible in adults who have taken 10g or more of paracetamol.
Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).
Risk factors
If the patient a) Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.
Or b) Regularly consumes ethanol in excess of recommended amounts.
Or c) Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms and signs
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion and have peaked after 4-6 days. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Treatment
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N- acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital.
Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit. Acute pancreatitis has been observed, usually with hepatic dysfunction and liver toxicity.

Caffeine
Symptoms and signs
Overdose of caffeine may result in epigastric pain, vomiting, diurese, tachycardia or cardiac arrhythmia, CNS stimulation (insomnia, restlessness, excitement, agitation, jitteriness, tremors and convulsions).
It must be noted that for clinically significant symptoms of caffeine overdose to occur with this product, the amount ingested would be associated with serious paracetamol-related liver toxicity.
Treatment
No specific antidote is available, but supportive measures such as beta adrenoceptor antagonists to reverse the cardiotoxic effects may be used.

Phenylephrine
Symptoms and signs
Phenylephrine overdosage is likely to result in effects similar to those listed under adverse reactions. Additional symptoms may include, irritability, restlessness, hypertension, and possibly reflex bradycardia. In severe cases confusion, hallucinations, seizures and arrhythmias may occur. However the amount required to produce serious phenylephrine toxicity would be greater than that required to cause paracetamol-related liver toxicity.
Treatment
Treatment should be as clinically appropriate. Severe hypertension may need to be treated with alpha blocking drugs such as phentolamine.
If overdose is confirmed or suspected, seek immediate advice from your Poison Centre and refer patient to nearest Emergency Medical Centre for management and expert treatment. This should happen even in patients without symptoms or signs of overdose due to the risk of delayed liver damage.

Chlorpheniramine
The estimated lethal dose of chlorphenamine is 25 to 50mg/kg body weight.
Symptoms and signs include sedation, paradoxical excitation of the CNS, toxic psychosis, convulsions, apnoea, anticholinergic effects, dystonic reactions and cardiovascular collapse including arrhythmias.
Treatment
Management should be as clinically indicated or as recommended by the national poisons centres where available.
Symptomatic and supportive measures should be provided with special attention to cardiac, respiratory, renal and hepatic functions and fluid and electrolyte balance. If overdosage is by the oral route, treatment with activated charcoal should be considered provided there are no contraindications for use and the overdose has been taken recently (treatment is most effective if given within an hour of ingestion). Treat hypotension and arrhythmias vigorously. CNS convulsions may be treated with i.v. diazepam.
Haemoperfusion may be used in severe cases.