Drug Induced Pellagra

The antituberculosis drug isoniazid (┬┐so-nicotinic acid hydrazide) can cause pellagra by forming a biologically inactive complex with pyridoxal phosphate, the metabolically active form of vitamin B6, and hence reducing the activity of kynureninase (Section 8.3.3.2). This isoniazid-induced pellagra responds to the administration of niacin supplements. However, isoniazid may also cause peripheral neuropathy, which responds to vitamin B6 and not niacin, and therefore it became usual to give vitamin B6 supplements together with isoniazid.

During the 1960s, the doses of isoniazid used in the treatment of tuberculosis were considerably reduced, as a result of the introduction of other effective antimycobacterial agents in therapeutic cocktails, and it was no longer thought necessary to give patients supplements of vitamin B6. There have been some reports of the development of pellagra in patients treated with relatively low doses of isoniazid; most patients were of Indian origin, and it is likely that they were genetically slow acetylators of isoniazid, so that an apparently low dose of the drug was, in fact, high. Up to 60% of Indians are slow acetylators of isoniazid.

Two further drugs are also capable of forming hydrazones with pyridoxal phosphate: the anti-Parkinsonian drugs Benserazide and Carbidopa. Both drugs inhibit the oxidative metabolism of tryptophan and cause reduced excretion of N1 -methylnicotinamide (Bender, 1980). Although no case of clinical pellagrahas been unequivocally reported, there have been a number of cases of pellagra-like conditions among patients receiving Benserazide or Carbidopa, and Parkinsonian patients treated with these drugs excrete less N1-methyl nicotinamide than control patients with similarly severe disease, but receiving different medication.

8.6 ASSESSMENT OF NIACIN NUTRITIONAL STATUS

Although the nicotinamide nucleotide coenzymes function in a large number of oxidation and reduction reactions, this cannot be exploited as a means of assessing the state of the body's niacin reserves, because the coenzymes are not firmly attached to their apoenzymes, as are coenzymes derived from thiamin (Section 6.5.3), riboflavin (Section 7.5.3), and vitamin B6 (Section 9.5.3), but act as cosubstrates of the reactions, binding to and leaving the enzyme as the reaction proceeds. No specific metabolic lesions associated with NAD(P) depletion have been identified.

The two methods of assessing niacin nutritional status are measurement of blood nicotinamide nucleotides and the urinary excretion of niacin metabolites, neither of which is wholly satisfactory.

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