Disipal (orfenadrin)./nThis question concerns general information on orphenadrine intoxication and

Fråga: Disipal (orfenadrin). This question concerns general information on orphenadrine intoxication and treatment.

Sammanfattning: Orphenadrine should be prescribed carefully to patients in whom it is considered that there is a real risk of self-poisoning. Orphenadrine poisoning should be treated in intensive care-units, early onset being decisive.

Svar: Orphenadrine, a methyl-derivative of the antihistamine diphenhydramine, shows anticholinergic and antihistamine effects. This compound is rapidly absorbed from the gastrointestinal tract, and is highly fat soluble leading to rapid diffusion into tissues. Most of the dose is metabolised and excreted in the urine, only a small fraction is excreted as parent drug. A half-life of 14 hours has been reported (1). Intoxication with orphenadrine is potentially serious because of low lethal dose, fast course and failure of therapy (2,3).

The initial dose is 150 mg daily gradually increased by 50 mg every 2 or 3 days; some patients may require a total of up to 400 mg daily (1). Central side effects (drowsiness, agitation, euphoria, hallucination and disorientation), and peripheral ones (hesitancy of micturition and dry mouth) mainly with doses up to 400 mg daily may appear. Coma with or without hypoventilation, seizures (epileptiform seizures in children), shock and dose-related cardiac rhythm disturbances can develop rapidly within one hour after overdosage (1-5,7,8). Several cases of death, have been reported (5-7). Death occurs after 3-5 hours after ingestion of a lethal dose (2-3 gram in adults) (2,3,6).

Although, several causes of death have been suggested (extensive cerebral oedema (5,6), centrilobular necrosis of the liver (6), pulmonary oedema (6)), cardiotoxic problems are the direct cause of death in orphenadrine intoxication (1,4,10,11).

A conservative-supportive treatment in intensive care-units is suggested (4,5,7). Diazepam has been found useful in epileptiform seizures and cases of cardiac symptoms (4,5). Physostigmine might be used in the treatment of hallucinations and disorientation, although this might be dangerous because of its side effects (convulsions, bradycardia, respiratory problems) (3,8). Moreover, early gastric lavage and administration of active-charcoal (9,10) can reduce the severity of the symptoms. Since, only a small fraction of the drug is in the plasma haemodialysis will not be of value (5).