Peripheral nervous systems isoniazid

Administer pyridoxine (vitamin Be) 25 to 50 mg daily or 50 to 100 mg twice weekly to all HIV-infected patients who are undergoing tuberculosis treatment with isoniazid to reduce the occurrence of isoniazid-induced side effects in the central and peripheral nervous system. 

Isoniazid is relatively safe, with determinants of adverse events being relatively predictable and addressable. In a study on 11,963 patients to evaluate the feasibility, treatment completion and adverse events of INH preventive therapy, age was identified as the main determinant of transaminase increase (OR 1.03, 95%CI 1.03-1.04), as were adverse events of the gastrointestinal (OR 1.02, 95%CI 1.02-1.03), central nervous (OR 1.02, 95%CI 1.02-1.05) and peripheral nervous systems (OR 1.04,95%CI 1.02-1.05) [43 ]. 

Peripheral neuropathy is observed in 10-20% of patients given dosages greater than 5 mg/kg/d, but it is infrequently seen with the standard 300-mg adult dose. Peripheral neuropathy is more likely to occur in slow acetylators and patients with predisposing conditions such as malnutrition, alcoholism, diabetes, AIDS, and uremia. Neuropathy is due to a relative pyridoxine deficiency. Isoniazid promotes excretion of pyridoxine, and this toxicity is readily reversed by administration of pyridoxine in a dosage as low as 10 mg/d. Central nervous system toxicity, which is less common, includes memory loss, psychosis, and seizures. These may also respond to pyridoxine. 

For recent skin-test converters of all ages, the risk of active TB outweighs the risk for drug toxicity.Pregnant women, alcoholics, and patients with poor diets who are treated with isoniazid should receive pyridoxine (vitamin Bg) 10-50 mg daily to reduce the incidence of central nervous system (CNS) effects or peripheral neuropathies. All patients who receive treatment of LTBl should be monitored monthly for adverse drug reactions and for possible progression to active TB. 

With respect to neurotoxins, there are a number of industrial chemicals (acrylamide, n-hexane, methyl n-butyl ketone, cresyl phosphate), pharmaceuticals (nitrofuradantoin, isoniazid), and pesticides (leptophos, Kepone ) which have been associated with neuropathic effects in humans (for reviews, see References 107,123, 124). Subchronic exposure studies in rodents and other animals such as cats have been used to identify and study the mechanism of action of neurotoxic chemicals which produce paralysis and behavioral changes in exposed animals. Studies are currently underway to evaluate the relative sensitivities of behavioral tests and morphological assays of peripheral and central nervous system axon morphology for detecting the earliest signs of chemically induced neuropathies. " ... 

Pyridoxine, vitamin B6, (10-50 mg/day) is coadministered with isoniazid to minimize the risk of peripheral neuropathy and central nervous system (CNS) toxicity in malnourished patients and those predisposed to neuropathy (e.g., slow acetylators, elderly, pregnant women, human immunodeficiency virus [HrV]-infected subjects, diabetics, alcoholics, and uremics). 

Nervous system The adverse effects of antituberculosis drugs on the nervous system have been reviewed [1 ]. Isoniazid is most often associated with nervous system reactions, most prominently peripheral neuropathy, psychosis, and seizures. Optic neuropathy can occur with ethambutol and ototoxicity and neuromuscular blockade with aminoglycosides. Cycloserine can cause psychosis and seizures, and the psychosis in particular limits its use. Fluoroquinolones are rare causes of seizures and delirium. Significant neurotoxicity has not been documented with newer forms of therapy under development. 

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