Pyridoxine Convulsions

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

About half of individuals who do not respond to pyridoxine will sustain ectopia lentisbj age 5-10 years. Indeed, the diagnosis commonly is made by an ophthalmologist. The median IQ score for B6 responsive and nonresponsive patients is 78 and 56 respectively. Some children present at 1-2 years with psychomotor retardation, convulsions (=20% of cases) and psychiatric difficulties such as depression and personality disorders (=50% of cases). 

High levels of homocysteine or one of its metabolites may directly affect brain function. The administration of homocysteine to rats induces grand mal convulsions, a phenomenon that is aggravated by either methionine or pyridoxine. Homocysteine-induced blockade of the y-aminobutyric acid (GABA) receptor may be involved. In addition, brain can oxidize homocysteine to homocys-teic acid, which has a glutamatergic activity. 

The last of the B vitamins to be identified in the water-soluble vitamin complex from milk was pyridoxine, vitamin B6 (Birch and Gyorgy, 1936). This was needed to prevent a type of dermatitis in rats which was different from pellagra or acrodynia and could be accompanied by convulsions. Much of the early work on the mode of action of this vitamin came from experiments on microbial metabolism (Chapter 6). 

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... 

After decontamination by emesis or lavage, patients should be carefully monitored for alterations in liver and kidney function, and treated symptomatically if necesseray. Seizures can be treated with anti-convulsant drugs. Because the toxin produces a deficiency of y-amino-butyric acid (GABA), specific treatment with pyridoxine (vitamin Bg) has been recommended. 

Adverse reactions include pyridoxine deficiency hyperglycemia gynecomastia peripheral neuropathy convulsions optic neuritis and atrophy memory impairment ... 

Obtain cultures Obtain cultures and determine susceptibility before treatment. Determine blood levels Determine blood levels weekly for patients having reduced renal function, for individuals receiving more than 500 mg/day, and for those with symptoms of toxicity. Adjust dosage to maintain blood level less than 30 mcg/mL. Anticonvulsant drugs or sedatives Anticonvulsant drugs or sedatives may be effective in controlling symptoms of CNS toxicity, such as convulsions, anxiety, and tremor. Closely observe patients receiving more than 500 mg/day for such symptoms. Pyridoxine may prevent CNS toxicity, but its efficacy has not been proven. 

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. 

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. 

AASA dehydrogenase deficiency (pyridoxine-responsive convulsions). 

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. 

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. 

Bessey OA, Adam DJD, and HansenAE (1957) Intake ofvitamin Be and infantile convulsions a first approximation to the requirements of pyridoxine in infants. Pediatrics 20, 33-44. 

Pyridoxine plays a role in (1) the control of the hypothalamo-pituitary end-organ system, (2) melatonin synthesis, and (3) convulsive seizure activity. Neurological deficits resulting from pyridoxine deficiency can largely be explained by decreased activity of glutamic acid decarboxylase, 5-hydroxytryptophan decarboxylase, and ornithine decarboxylase (Dakshinamurti et al., 1990). The products of these... 

When pyridoxine deficiency is induced in pregnant rats, spontaneous convulsions are seen in the offspring at 3-4 days of age. Seizures are of short duration. 

Pyridoxine (Bg) Pyridoxal phosphate Group transfer to or from amino acids Depression, confusion, convulsions... 

Hematological Disorders. Seventeen boys under 4 years of age were studied by Rabe and Plonko (Rl) for evidence of pyridoxine need. Four of the children had hypochromic microcytic anemia, 4 had convulsions, and 9 suffered from miscellaneous acute infectious illnesses. 

The discrepancies between the amount of pyridoxine required to suppress abnormal xanthurenic acid excretion and to eliminate the convulsions in these infants suggests that an aberrant metabolism of trypto-... 

I.6. Various Diseases. Abbassy et al. (Al) observed in 12 cases of malnutrition (including kwashiorkor), toxic dyspepsia, 8 cases of acute nephritis, 8 cases of infective hepatitis, and muscular dystrophy an increased spontaneous excretion of xanthurenic acid, the amount of which was found to depend on the severity of the case. In all these cases, with the exception of acute nephritis and hepatitis, the amount of xanthurenic acid was restored to normal levels after vitamin Be therapy. In 8 children with mental retardation, cerebral palsy, recurrent convulsions, 5 with nephrotic syndrome, and 5 with pellagra the amount of xanthurenic acid spontaneously excreted was found to be within the normal range, indicating that pyridoxine is probably not concerned in these cases. 

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. 

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. 

Hunt AD Jr, Stokes J Jr, McCrory WW, Stroud HH. Pyridoxine dependency report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics 1954 13(2) 140-5. 

Because of inadequate diets, some infants suffer from severe vitamin B deficiencies that can lead to cpilepsy-like convulsive seizures, and the convulsions can be controlled by treatment with pyridoxine. The convulsions are believed to be due to below-normal availability of the central nervous... 

There are several vitamin Bg-responsive inborn errors of metabolism that include (1) cases of infantile convulsions in which the apoenzyme for glutamate decarboxylase has a poor affinity for the coenzyme (2) a type of chronic anemia in which the number but not morphological abnormality of erythrocytes is improved by pyridoxine supplementation (3) xanthurenic aciduria in which affinity of the mutant kynureninase for PLP is decreased (4) primary cystathion-inuria caused by similarly defective cystathionase and (5) homocystinuria in which there is less of the normal cystathionine synthetase. In these cases increased levels (200 to lOOOmg/day) of administered vitamin Bg are required for life. Low vitamin Bg status (together with low vitamin B12 and folate status) in humans has been linked to hyperho-mocysteinemia and as an independent risk factor for cardiovascular disease. ... 

Pyridoxine 10-50 mg Infantile convulsions Perhaps glutamate decarboxylase... 

Pyridoxine (B6) Dermatitis, neuritis, convulsions, microcytic anemia Plasma B Sensory neuropathy (high supplement intake)... 

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