Pyridoxin deficiency

JONE 0 L, GONZALEX V (1978) Pyridoxine deficiency, a new factor in daiabetic Neuropathy. JAmer Podiatory Assoc, 68 646-53. 

Therapy with INH results in a transient elevation in serum transaminases in 12% to 15% of patients and usually occurs within the first 8 to 12 weeks of therapy. Risk factors for hepatotoxicity include patient age, preexisting liver disease, and pregnancy or postpartum state. INH also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, seizures, and coma. Patients with pyridoxine deficiency, such as alcoholics, children, and the malnourished, are at increased risk, as are patients who are slow acetylators of INH and those predisposed to neuropathy, such as those with diabetes. 

The association between vitamin B6 deficiency and transamination emerged from 1945 when Schlenk and Fisher noted that pyridoxine-deficient rats had a diminished capacity for transamination. In the same year Gunsalus and his colleagues found transamination in Streptococcus faecalis depended on pydridoxal phosphate. The properties of the heat-stable component in purified glutamic-oxaloacetate transaminase were similar to those of pydridoxal phosphate. Later pyri-doxal phosphate was established as an essential coenzyme in many amino acid transformations. 

Nutritional Folate deficiency Iron deficiency Vitamin Bi (thiamine) deficiency Vitamin B2 (riboflavin) deficiency Vitamin Bg (pyridoxine) deficiency Vitamin B12 (cyanocobalamin) deficiency... 

Uterine fibroids Preexisting uterine leiomyomata (uterine fibroids) may increase in size. However, there is no evidence of this with low-dose hormonal contraceptives. Depression The incidence of depression in OC users ranges from less than 5% to 30%. Pyridoxine deficiency may be a factor in the depression. Women who become significantly depressed when using hormonal contraceptives should stop the... 

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

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-... 

Sideroblastic anemia is characterized by excessive iron in the cells that cannot be incorporated into porphyrin to form heme. Although it is rare, the most common cause of sideroblastic anemia is alcoholism and pyridoxine deficiency. Pyridoxine is required for the formation of pyri-doxal phosphate, a coenzyme in porphyrin synthesis. 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including metabolism of proteins, carbohydrates, and fats. Aids in the breakdown of glycogen and in the synthesis of gamma-aminobutyric acid in the CNS. Therapeutic Effect Prevents pyridoxine deficiency. Increases the excretion of certain drugs, such as iso-niazid, that are pyridoxine antagonists. 

Although the MAOIs can have serious and potentially life-threatening adverse effects, it is the more common and less dramatic side effects that often lead to the discontinuation of MAOIs. These side effects include orthostatic hypotension, drowsiness, insomnia, edema, weight gain, sexual dysfunction, and precipitation of mania. Rare side effects include hepatitis and leukopenia. Parasthesias may develop secondary to a MAOI-induced pyridoxine deficiency, which responds to oral pyridoxine supplementation. Overall, phenelzine appears to be more sedating, whereas trancylpromine is more activating because of its stimulant-like properties. Meclobomide has more excitatory side effects, such as restlessness and insomnia. 

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. 

Miscellaneous other reactions include hematologic abnormalities, provocation of pyridoxine deficiency anemia, tinnitus, and gastrointestinal discomfort. Isoniazid can reduce the metabolism of phenytoin, increasing its blood level and toxicity. 

Isoniazid (INH) Minimal Milk concentrations equal maternal plasma concentrations. Possibility of pyridoxine deficiency developing in the infant. 

Most antibiotics taken by nursing mothers can be detected in breast milk. Tetracycline concentrations in breast milk are approximately 70% of maternal serum concentrations and present a risk of permanent tooth staining in the infant. Isoniazid rapidly reaches equilibrium between breast milk and maternal blood. The concentrations achieved in breast milk are high enough so that signs of pyridoxine deficiency may occur in the infant if the mother is not given pyridoxine supplements. 

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. 

Excessive central stimulation, usually exhibited as tremors, insomnia and hyperhidrosis, can occur following therapeutic doses of the MAOIs, as can agitation and hypo manic episodes. Peripheral neuropathy, which is largely restricted to the hydrazine type of MAOI, is rare and has been attributed to a drug-induced pyridoxine deficiency. Such side effects as dizziness and vertigo (presumably associated with hypotension), headache, inhibition of ejaculation (which is often also a problem with the TCAs), fatigue, dry mouth and constipation have also been reported. These side effects appear to be more frequently associated with phenelzine use. They are not associated with any antimuscarinic properties of the drug but presumably arise from the enhanced peripheral sympathetic activity which the MAOIs cause. 

A deficiency syndrome is not well-defined in humans. Since pyridoxine deficiency often produces nicotinic acid deficiency, pellagra-like clinical manifestations may occur.29 The recommended daily allowance is 1.5 to 2 mg.112... 

Lakshmi, R. et al., Effect of riboflavin or pyridoxine deficiency on inflammatory response, Indian. J. Biochem. Biophys., 28, 481, 1991. 

Authors who reported a case of carpal tunnel syndrome due to pyridoxine deficiency in a patient taking tranylcypromine (SEDA-9, 21) later collected data (6) on six patients taking phenelzine (up to 75 mg/day for up to 4 months). All developed low concentrations of pyridoxine and a variety of symptoms, including numbness, paresthesia, and edema of the hands, as well as an electric shock sensation in the head, neck, and arms. The symptoms resolved completely after the addition of pyridoxine 150-300 mg/day to the treatment regimen. 

Stewart JW, Harrison W, Quitkin F, Liebowitz MR. Phenelzine-induced pyridoxine deficiency. J Clin Psychopharmacol 1984 4(4) 225-6. 

Coon WW and Nagler E (1969) The tryptophan load as a test for pyridoxine deficiency in hospitalized patients. AnnaU of the New York Academy of Sciences 166,30-43. 

Trakatellis A, Dimitriadou A, and Trakatelli M (1997) Pyridoxine deficiency new approaches in immunosuppression and chemotherapy. Postgraduate Medical Journal 73,617-22. 

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... 

Fig. 4 Decreased dendritic arborisation in pyridoxine deficiency. Figure shows reduced Purkinje cells arborisation at 12 and 15 days in rat pups fed 0.6,1.0, and 7 mg pyridoxine/Kg diet (modified from Chang et al., 1981)...

The hypothalamus contains high concentrations of the monoamines dopamine and serotonin and these neurotransmitters have inhibitory or excitatory effects, respectively, on the anterior pituitary. For example, thyroid-stimulating hormone (TSH) secretion is increased by serotoninergic and decreased by dopaminergic activation. Pyridoxine deficiency in rats is associated with low levels of PLP in the hypothalamus, with no change in dopamine concentrations, but decreased levels of serotonin (Dakshinamurti et al., 1990). This correlates with decreased thyroid status and decreased pituitary TSH. Treatment with pyridoxine returns these parameters to normal. 

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. 

Excess xanthurenate in the urine. Xanthure-nate levels in the urine increase with vitamin B6 deficiency because B (as pyridoxal phosphate) is necessary for the further chemical transformation of 3-hydroxykynurenine. Pyridoxine deficiency may be detected by giving the patient a loading dose of tryptophan. If pyridoxine deficiency is present, there will be a detectable excess of xanthurinate in the urine. Oral contraceptives may increase urinary xanthurenate levels, possibly... 

In 1942 it was shown that the urine of pyridoxine-deficient rats contained large amounts of xanthurenic acid (L2). This was the starting point for studies on the interrelationship among vitamin Be, tryptophan, and protein metabolism. 

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