Pyridoxine, with isoniazid therapy

ALA synthase, the rate-limiting enzyme, requires pyridoxine (vitamin B ). Deficiency of pyri-doxine is associated with isoniazid therapy for tuberculosis and may cause sideroblastic anemia with ringed sideroblasts. 

If isoniazid is implicated in optic neuropathy or other neurologic signs, then pyridoxine (vitamin Bg), 25 to 100 mg/day, may be used. Prophylactic administration of this agent can be combined with isoniazid and monoamine oxidase inhibitor therapy. 

Peripheral neuropathy has been observed as a complication in tuberculosis therapy with isonicotinic acid hydrazide (isoniazid), especially when large doses have been employed (B14). This complication of isoniazid therapy has been largely eliminated by simultaneous administration of pyridoxine. These observations have prompted studies on the urinary excretion of xanthurenic acid as an index of the antipyridoxine activity of isoniazid. The excretion of an excess of vitamin Be as such... 

Therapy. A true deficiency of vitamin B5 is rare. Neurological symptoms associated with pellagra and beri-beri seem to be improved with pyridoxine. Doses of pyridoxine (40-150 mg daily) are used for the peripheral neuritis due to treatment with isoniazid and related compounds. Pyridoxine has also been used for nausea and vomiting due to a variety of conditions. It has been recommended for the treatment of agranulocytosis and seborrhoeic dermatitis (Marks, 1975). 

The addition of pyridoxine to usual doses of isoniazid of 5 mg/kg/day in adults and 8-10 mg/kg/day in children markedly reduces neurotoxicity (9). Adherence to therapy is improved by prescribing combined tablets containing 20 mg of pyridoxine per 100 mg of isoniazid. In otherwise healthy people, prescription of pyridoxine is not mandatory. However, it should be routinely given to malnourished patients and those predisposed to neuropathy (for example pregnant women, elderly people, and people with diabetes, alcoholism, or uremia) (7). 

Vitamin deficiency can result from treatment with certain drags. Thus, destruction of intestinal microorganisms by antibiotic therapy can produce symptoms of vitamin K deficiency. Isoniazid, used to treat tuberculosis, is a competitive inhibitor of pyridoxal kinase, which is needed to produce pyridoxal phosphate. Isoniazid can produce symptoms of pyridoxine deficiency. To prevent this, pyridoxine is often incorporated into isoniazid tablets. Methotrexate and related folate antagonists act by competitively inhibiting dihydrofolate reductase (Chapter 27). 

Therapy with ethambutol results in an increased concentration of urate in the blood in about 50% of patients, owing to decreased renal excretion of uric acid. The effect may be detectable as early as 24 hours after a single dose or as late as 90 days after treatment is started. This untoward effect is possibly enhanced by isoniazid and pyridoxine. 

THERAPEUTIC USES Isoniazid is the most imfwrtant drug for the treatment of tuberculosis. Toxic effects are minimized by prophylactic therapy with pyridoxine and careful patient surveillance. For treatment of active infections, the drug is combined with another agent, although it is... 

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