Porphyria acute intermittent, barbiturates precipitating

Acute intermittent porphyria is a dominantly inherited partial deficiency of porphobilinogen deaminase, and causes axonal polyneuropathy. Acute intermittent porphyria is caused by partial deficiency of porphobilinogen deaminase, an enzyme required for heme biosynthesis. Patients may present with acute abdominal pain, rapidly progressive sensorimotor axonal polyneuropathy or psychosis, and have elevated concentrations of the heme precursor 8-amino-levulinic acid in their urine. Symptoms may be precipitated by treatment with barbiturates or other drugs and are suppressed by treatment with hematin [59]. 

Barbiturates may precipitate episodes of acute intermittent porphyria (AIP) and their use is contraindicated in patients who are predisposed to this condition. Some animal models indicate that ketamine, etomidate, and the benzodiazepines may be porphyrinogenic and propofol is considered to be the intravenous anaesthetic of choice in AlP-prone patients. 

Barbiturates reduce hepatic blood flow and glomerular filtration rate, but these drugs produce no adverse effects on hepatic or renal function. Barbiturates can exacerbate acute intermittent porphyria by inducing the production of hepatic ct -aminolevulinic acid (ALA) synthase (see Chapter 22). On rare occasions, thiopental has precipitated porphyric crisis when used as an induction agent in susceptible patients. 

Enzyme inducers, such as phenytoin, carbamazepine, and barbiturates, can precipitate attacks in patients with acute intermittent porphyria. 

Tuberculous patients lacking in liver N-acetyl transferase who are treated with isoniazid are likely to develop polyneuritis (39). An enzyme abnormality is also responsible for the precipitation of acute intermittent porphyria by the barbiturate drugs (40). Likewise, the rare hereditary resistance to coumarin anticoagulant drugs is thought to be due to an enzyme deficiency (41). 

It is of interest that those who inherited acute intermittent porphyria and variegate porphyria suffered no biological disadvantage from the natural environment and bred as well as the normal population until the introduction of barbiturates and sulphonamides. They are now at serious disadvantage, for many other drugs can precipitate fatal acute attacks. 

Other adverse effects Barbiturates and carbamates (but not benzodiazepines, buspirone, zolpidem, or zaleplon) induce the formation of the liver microsomal enzymes that metabolize dmgs. This enzyme induction may lead to multiple drug interactions. Barbiturates may also precipitate acute intermittent porphyria in susceptible patients. Chloral hydrate may displace coumarins from plasma protein binding sites and increase anticoagulant effects. 

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