Convulsion isoniazid

The answer is b. (Hardmanr p 1158.) Isoniazid inhibits cell-wall synthesis in mycobacteria. Increasing vitamin B6 levels prevents complications associated with this inhibition, including peripheral neuritis, insomnia, restlessness, muscle twitching, urinary retention, convulsions, and psychosis, without affecting the antimycobacterial activity of INH. 

Pyridoxine (B ) Pyridoxal-P (PLP) Aminotransferases (transaminase) AST (GOT), ALT (GPT) 8-Aminolevulinate synthase Protein catabolism Heme synthesis MCC isoniazid therapy Sideroblastic anemia Cheilosis or stomatitis (cracking or scaling of lip borders and corners of the mouth) Convulsions... 

It is indicated to prevent and treat isoniazid, hydralazine, penicillamine and cycloserine induced neurological disturbances, mental symptoms in women on oral contraceptives, pyridoxine responsive anaemia and homocystinuria, morning sickness and hyperemesis gravidarum, convulsions in infants and children. 

Bilobalide, a main constituent of the terpene fraction of the EGb, possesses anticonvulsant activity against convulsions induced by pentylenetetrazol, isoniazid, 4-0-methylpyridoxine, and electroshock. Reduced durations of convulsions and prolonged onset time of convulsions induced by chemical convulsants and electroshock were observed in mice treated orally with bilobalide (30 mg/kg/day, for 4 days). However, bilobalide has no protective effect against bicuculline- and strychnine-induced convulsions [99,100]. 

Other toxicants, including some drugs, will indirectly affect receptors. For example, isoniazid and other hydrazides and hydrazines indirectly inhibit the GABAa receptor by inhibiting the synthesis of GABA, causing convulsions at high doses (see chap. 7). 

Isoniazid is bactericidal for growing tubercle bacilli, is absorbed orally, and is metabolized by acetylation. It is a structural analogue of pyridoxine and may cause pyridoxine deficiency, peripheral neuritis and, in toxic doses, pyridoxine-responsive convulsions. Its mechanism of action is not known. 

Benzodiazepine derivatives are thought to exert their anticonvulsant activity by facilitating GABAer-gic transmission. Substances that inhibit the synthesis of GABA (e.g., isoniazid) or block the GABA recognition site (e.g., bicuculline) cause convulsions (Figure 65.6). 

Among the many toxicants that cause convulsions are chlorinated hydrocarbons, amphetamines, lead, organophosphates, and strychnine. There are several levels of coma, the term used to describe a lowered level of consciousness. At level 0, the subject may be awakened and will respond to questions. At level 1, withdrawal from painful stimuli is observed and all reflexes function. A subject at level 2 does not withdraw from painful stimuli, although most reflexes still function. Levels 3 and 4 are characterized by the absence of reflexes at level 4, respiratory action is depressed and the cardiovascular system fails. Among the many toxicants that cause coma are narcotic analgesics, alcohols, organophosphates, carbamates, lead, hydrocarbons, hydrogen sulfide, benzodiazepines, tricyclic antidepressants, isoniazid, phenothiazines, and opiates. 

Isoniazid Isoniazid is incompatible with sugars. Isoniazid overdose may be severe to fatal, and treatment is symptomatic and supportive, including stomach wash for control of convulsions and treating metabolic acidosis. Administration of pyridoxine and hemodialysis may be needed. Isoniazid interacts with carba-mazepine, phenytoin, diazepam, triazolam, chlorzoxazone, theophylline, ethosux-imide, enflurane, cycloserine, and warfarin. 

Isoniazid can cause convulsions and therefore should be prescribed with caution in patients with epilepsy. Isoniazid is an enzyme inhibitor and may increase carbamazepine levels. Rifampicin is an enzyme inducer and may decrease carbamazepine levels. 

Cotte and Plantier (Cll) also applied tryptophan loading (0.54 mg/ kg) as a tool for detecting pyridoxine deficiency in children by means of xanthurenic acid determination. The investigation was extended to normal controls, tuberculous children treated with isoniazid, 9 with convulsive syndrome and infantile seizures, 2 with Wilson s disease, and 2 with Fanconi s anemia. 

Williams and Wiegand (W12), using tryptophan-loaded dogs, confirmed Biehl and Vilter s (B14) findings in man that isoniazid increases urinary xanthurenuria. In addition they found that three other convulsant hydrazides (thiocarbohydrazide, thiosemicarbazide, and semicarbazide) produced xanthurenuria in dogs somewhat similar to that produced by isoniazid. 

Isoniazid is a structural analogue of pyridoxine and accelerates its excretion, the principal result of which is peripheral neuropathy with numbness and tingling of the feet, motor involvement being less common. Neuropathy is more frequent in slow acetylators, malnourished people, the elderly and those with HIV infection, liver disease and alcoholism. Such patients should receive pyridoxine lOmg/d by mouth, which prevents neuropathy and does not interfere with the therapeutic effect some prefer simply to give pyridoxine to all patients. Other adverse effects include mental disturbances, incoordination, optic neuritis and convulsions. 

A-39 Deficiency of Vitamin B6 can cause convulsions, lethargy, mental changes retardation, anemia, and skin inflammation. Deficiencies of vitamin Be are rare and usually are related to an overall deficiency of all the B-complex vitamins. Isoniazid (see niacin deficiencies above) and penicillamine (used to treat rheumatoid arthritis and cystinurias) are two drugs that complex with pyridoxal and pyridoxal phosphate resulting in a deficiency in this vitamin. 

Ethionamide, which has bacteriostatic actions against M. tuberculosis (0.5 to 1 g/day in divided doses) is indicated in the treatment of tuberculosis where first-line drugs such as isoniazid and rifampin have failed. The side effects of ethionamide may include nausea and vomiting, diarrhea, metallic taste, hepatitis, jaundice, stomatitis, depression, drowsiness, asthenia, peripheral neuritis, olfactory disturbances, diplopia, blurred vision, optic neuritis, convulsions, postural hypotension, thrombocytopenia, gynecomastia, impotence, menorrhagia, or diabetes mellitus. 

Isoniazid may precipitate convulsions, usually in patients with known seizure disorders. Optic neuritis also has occurred. Muscle twitching, dizziness, ataxia, paresthesias, stupor, and potentially fatal encephalopathy are other manifestations of neurotoxicity. A number of mental abnormalities may appear, including euphoria, transient memory inpairment, loss of self-control, and psychosis. 

Frappaz D, Biron P, Biron E, Amrane A, Philip T, Brunat-Mentigrty M. Toxicite neurologique severe (coma, convulsions, neuropathic motrice distale) secondaire a I association d une intoxication accid telle a I isoniazide (ENH) et d un protocole comportant de fortes doses de vincristine (VCR). Pediatrie (1984) 39,133-40. 

Six cases of isoniazid-induced convulsions were described by Coyer and Nicholson (9 ), in patients who had taken overdoses. The value of vitamin Be in the prevention and treatment of acute isoniazid poisoning was emphasized in this paper. In one of the cases reported, a single large intravenous dose of Be resulted in a dramatic cessation of seizures. These authors suggest that the dose of Be given over the first few hours after ingestion of the isoniazid should approach in weight the total amount of the latter estimated to have been taken. 

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