Central nervous system isoniazid

Isoniazid does not bind to serum proteins it diffuses readily into all body fluids and cells, including the caseous tuberculous lesions. The drug is detectable in significant quantities in pleural and ascitic fluids, as well as in saliva and skin. The concentrations in the central nervous system (CNS) and cerebrospinal fluid are generally about 20% of plasma levels but may reach close to 100% in the presence of meningeal inflammation. 

Isoniazid is readily absorbed from the gastrointestinal tract. A 300-mg oral dose (5 mg/kg in children) achieves peak plasma concentrations of 3-5 mcg/mL within 1-2 hours. Isoniazid diffuses readily into all body fluids and tissues. The concentration in the central nervous system and cerebrospinal fluid ranges between 20% and 100% of simultaneous serum concentrations. 

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. 

Isoniazid plus phenytoin Central nervous system toxicity Slow acetylators... 

Ethambutol [e THAM byoo tole] is bacteriostatic and specific for most strains of M- tuberculosis and M- kansasii. Resistance is not a serious problem if the drug is employed with other antituberculous agents. Ethambutol can be used in combination with pyrazinamide, isoniazid, and rifampin to treat tuberculosis. Absorbed on oral administration, ethambutol is well distributed throughout the body. Penetration into the central nervous system (CNS) is therapeutically adequate in tuberculous meningitis. Both parent drug and metabolites are excreted by glomerular filtration and tubular secretion. The most important adverse effect is optic neuritis, which results in... 

Ethambutol is the most likely drug to cause visual disturbances. Isoniazid is associated with poljmeuritis and reactions of the central nervous system. Streptomycin can cause eighth nerve toxicity. 

Pyridoxine hydrochloride is indicated in the treatment and prevention of vitamin deficiency. It is also approved forcon-current administration with isoniazid and cycloserine to decrease their toxicity. Concurrent administration of pyridux-ine hydrochloride and Icvodopa is nut recommended. The decarboxylation of levudopa to dopamine in the peripheiy is increased by pyridoxine. so that less levodupa reaches IIk central nervous system. 

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 Central nervous system toxicity due to isoniazid has been reported in a child [69 ]. 

Hawkes M, Kitai L Blaser S, Cohen E, Bitnun A, Fluss J, Tran D. Neuroimaging findings in isoniazid central nervous system toxicity, presumed intramyelinic edema. Eur J Paediatr Neurol 2008 12(6) 512-5. 

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 ]. 

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