Pyridoxine central nervous system

The answer is e. (Hardman, p 1563 ) The toxicity of INI I is mainly on the peripheral and central nervous systems (PNS, CNS). This is attributable to competition of 1NH with pyridoxal phosphate for apotryp-tophanase. This results in a relative deficiency of pyridoxine, which causes peripheral neuritis, insomnia, and muscle twitching among other effects. 

Head trauma, meningitis, childhood fevers, brain tumors, and degenerative diseases of the cerebral circulation are conditions often associated with the appearance of recurrent seizures that may require treatment with anticonvulsant drugs. Seizures also may be a toxic manifestation of the action of central nervous system (CNS) stimulants and certain other drugs. Seizures often occur in hyperthermia (febrile seizures are very common in infants) sometimes in eclampsia, uremia, hypoglycemia, or pyridoxine deficiency and frequently as a part of the abstinence syn-... 

Pyridoxine vitamin Bf) deficiency symptoms are generally expressed as alterations in the skin, blood, and central nervous system. Symptoms include sensory neuritis, mental depression, and convulsions. Hypochromic, sideroblastic anemia also may result. Since pyridoxine is required for the conversion of tryptophan to diphos-phopyridine and triphosphopyridine nucleotides, pellagralike symptoms can occur with vitamin Bg deficiency. This deficiency is found most often in conjunction with other B complex deficiencies. 

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. 

Paradoxically, pyridoxine itself can also cause pathology in the central nervous system consisting of necrosis of dorsal root ganglia neurons and a centrifugal axonal atrophy and breakdown of peripheral and central sensory axons (Xu et al., 1989). This may occur at doses as low as 200-500 mg/d. However, in clinical trials using 100-150 mg/d to treat carpal tunnel syndrome, no toxicity was reported, suggesting that this a safe dose in adults. On the other hand, there are insufficient data to recommend long-term use of pyridoxine in children. 

Pyridoxine interferes with the desired nervous system effect of levodopa (64,65), since it is a co-decarboxylase, which facilitates the transformation of levodopa to dopa outside the central nervous system. 

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. 

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). 

Since completion of this manuscript, a number of reviews have appeared covering various aspects of Parkinsonism such as the use [557], mode of action [558], metabolism [559], and side-effects [560, 561] of L-dopa and the antagonism of its effects by pyridoxine [562], Other useful sources include general accounts of Parkinsonian therapeutics [563-565], the role [558, 566] and distribution [567] of dopamine in the central nervous system, and the pharmacology and biochemistry of 6-hydroxydopamine [567, 568]. Furthermore, there appear to be two forms of Parkinsonism, one more refractory to nicotine than the other [569], and it is significant that nicotine is a known cholinergic tremorogen and produces a Parkinsonian syndrome in animals [8]. 

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. 

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