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THE PORPHYRIAS
A MEDICAL GUIDE
The Porphyrias are a heterogeneous group of either inherited or acquired disorders of haem biosynthesis. In these diseases, specific abnormalities of enzymes in the biosynthetic pathway cause generalised clinical abnormalities. They are classified, as shown below, into acute and non-acute porphyria.
ACUTE
PORPHYRIA |
ACUTE INTERMITTENT PORPHYRIA
(Swedish Porphyria)
VARIEGATE PORPHYRIA
(South African Genetic Porphyria)
HEREDITARY COPROPORPHYRIA
(Coproporphyria)
PLUMBOPORPHYRIA
(ALA Dehydratase deficiency)
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NON-ACUTE
PORPHYRIA |
PORPHYRIA CUTANEA TARDA
(Cutaneous Hepatic Porphyria:
Symptomatic Porphyria)
ERYTHROPOIETIC PROTOPORPHYRIA
(Erythrohepatic Porphyria)
CONGENITAL PORPHYRIA
(Gunther's disease:
Erythropoietic Porphyria) |
The effects of drugs are most important in the acute porphyria, which are examples of 'Toxico-genetic diseases'. Patients with the acute form of these disorders are at risk of developing life-threatening attacks of porphyria on exposure to certain commonly prescribed drugs. 'Toxico-genetic diseases' - are diseases, genetically acquired, which show an idiosyncratic reaction to drugs. All the acute porphyria are inherited as mendelian autosomal dominants, and each may be linked to lowered activity of one of the enzymes of the haem biosynthetic pathway: in Acute Intermittent Porphyria - a decrease in porphobilinogen deaminase: in Variegate Porphyria - a decrease in protoporphyrinogen oxidase, and in Hereditary Coproporphyria - a decrease in coproporphyrinogen oxidase.
Features of the Acute Attack:
Attacks of Acute porphyria vary in their clinical presentation. Severe abdominal pain, vomiting and constipation, with tachycardia and hypertension, are the commonest presenting features. Peripheral neuropathy may develop and lead to fatal respiratory paralysis. Tachycardia and hypertension are usually present, and hypertensive encephalopathy may develop. Besides hypertension, severe postural hypotension, resulting in syncope may occur. Hypertension may persist to some extent between attacks. Other manifestations of autonomic dysfunction, such as profuse sweating, pallor and pyrexia may also occur.
Severe hyponatraemia, due to inappropriate secretion of antidiuretic hormone, complicates some attacks and sometimes presents as convulsions or deterioration in the conscious level. Another feature of involvement of the Central Nervous System is mental disturbance including agitation, mania, depression, auditory and visual hallucinations, and schizophrenic-like behaviour. Grand-mal convulsions are not uncommon at the height of an attack and may persist between attacks.
In Variegate Porphyria, and in Hereditary Coproporphyria, there may also be skin involvement, with development of solar photosensitivity.
Precipitating Factors:
It should be emphasised that most subjects who have inherited one of these diseases will enjoy normal health and go through life without any knowledge of his or her disorder or ever experiencing an acute attack. Such, is the latent phase of the disease. All porphyrics, however, are at risk of developing an attack if exposed to various precipitating factors. Drugs are the most common precipitating agents. Other factors that may trigger attacks, include alcohol ingestion, reduced caloric intake, due to fasting or dieting, and infection. We have also noted that smoking can cause more frequent attacks. Hormones are also important. Attacks are more common in females and, rarely, occur before puberty or after the menopause. Pregnancy and oral contraceptives may also precipitate attacks. Some women experience regular attacks, commencing in the week prior to the onset of menstruation. Although most of the drugs incriminated as porphyrinogenic are lipophilic and inducers of the hepatic mixed function oxidase system, it is impossible to reliably predict from chemical structure whether a drug will be safe for use in the porphyric patient.
The Drug Lists:
It should be borne in mind that such Lists are far from encyclopaedic, that new drugs are constantly being introduced to the pharmacopoeia, and that any form of combined preparation must be viewed with suspicion, since little is known about metabolic interactions in these diseases. The ultimate aim of investigative programs in the porphyria is to identify as many as possible of the cases latent for these diseases, using sensitive enzyme-screening tests, and by a program of education, especially on drug usage, transform these potentially fatal conditions to mere genetic curiosities.
EVALUATION OF DRUGS FOR PORPHYRIC PATIENTS
Extensive lists of contraindicated drugs are available at the following website: http://www.drugs-porphyria.org/
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