Drug treatment in acute porphyria.

Abstract

The acute hepatic porphyrias are rare pharmacogenetic diseases inherited as autosomal dominant conditions of low penetrance. The genetic defect is a 50% deficiency of an enzyme of the haem biosynthetic pathway. Patients may develop 'neurovisceral attacks' which include severe abdominal pain, neuropsychiatric manifestations and potentially fatal respiratory paralysis. Attacks occur generally after puberty, are much commoner in females and may be precipitated by endogenous hormonal changes, dieting, alcohol, severe infections, and many drugs. Treatment includes analgesia, early administration of haem, and general supportive measures. Patients are at greater risk of a severe attack on first presentation since an abdominal emergency may be simulated and inappropriate medication, including that for general anaesthesia may exacerbate the crisis. The urine should be tested for raised porphobilinogen, which is pathognomonic of the acute attack, if there is the slightest doubt about diagnosis. The genotype of blood relatives of index cases must be determined so that carriers may avoid drug and other precipitants. Some drugs have been established as safe or unsafe by clinical use, but information about many drugs is not available or is based only on their properties in rodents or in tissue culture systems. The relevance of these to the human condition remains controversial, but drugs shown to be porphyrinogenic in animal systems should be avoided if there is a known safe alternative. Where it is essential to use a drug not known to be safe, close biochemical and clinical observation may warn of an impending attack.