Pyridoxine deficiency effect

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. 

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. 

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

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. 

In 20-25% of cases, side effects are observed, depending mainly on the dose (hypersensitivity reactions, aphthous lesions, arthralgia, nausea, fever). All in all, treatment of Wilson s disease with penicillamine is considered to be successful and safe. If jrenicill-amine is not well tolerated or if serious side effects are observed (e.g. kidney or bone-marrow damage, polyneuropathy, pemphigus), treatment must be discontinued. Penicillamine usually causes pyridoxin deficiency, so that substitution (25—40 mg/day) is recommended, particularly as chronic liver damage also leads to vitamin Bg deficiency. If necessary, electrolytes and trace elements also have to be substituted. 

Penicillamine, both L-penicillamine and the racemic mixture, strongly inhibit pyridoxal-dependent enzymes, cause pyridoxine deficiency in animal experiments, and are neurotoxic. Although this effect is much weaker with D-penicillamine, a few case reports have shown that D-penicillamine can also occasionally cause a polyneuropathy, as either a toxic or an allergic reaction (69-72). Rarely, an optic neuropathy (73) or a polyradiculoneuropathy (Guillain-Barre syndrome) (74,75) can occur. 

Ludwig S, Kaplowitz N. Effect of pyridoxine deficiency on serum and liver transaminases in experimental liver injury in the rat. Gastroenterology 1980 79 545-9. 

Injected tryptophan causes a rise in erythrocyte DPN in the rat (562). The problem was taken up by Elvehjem and his school (c/. review, 224), who at first found tryptophan to be more active than nicotinamide in stimulating synthesis of rat-liver DPN and TPN (924, 925). Nicotinamide had, however, a sparing effect in young, but not in adult, rats (925). In pyridoxine deficiency conversion of tryptophan to pyridine nucleotides... 

Vitamin status also may be affected by drugs (Table 135-15). For example, sulfasalazine therapy has been noted to cause a decrease in folic acid, isoniazid therapy causes pyridoxine deficiency, and furosemide therapy may result in decreased thiamin concentrations. Furthermore, some drug therapy outcomes may be affected by vitamin intake. The ingestion of megadoses of folic acid may decrease methotrexate s therapeutic effect, whereas changes in an individual s usual vitamin K intake may cause variability in warfarin s anticoagulation effects. 

B5. Bhagavan, H. M., and Coursin, D. B., Effects of pyridoxin deficiency and DL-p-cjhlorophenylalanine administration to rats on 5-hydroxytryptamine and noradrenaline concentrations in brain and 5-hydroxytryptamine concentration in blood. Biochetn. J. 134, 763-767 (1973). 

Vitamin Be, see also under Pyridoxine deficiency, manifestations, VIII, 56 fat metabolism and, VIII, 56 physiological effects, VIII, 56 terminology, VIII, 56 Vitamin Bio, activity, VIII, 11 nature of, VI, 20 Vitamin Bn, activity, VIII, 11 nature of, VI, 20... 

The deleterious effects of pyridoxine deficiency have been observed by experimentation on animals, by observations of people with deficient diets, and by experimentation with antivitamins in humans. Depending upon the animals used in the experiments, at least four major groups of lesions have been attributed to pyridoxine deficiency dermatitis involving the extremities, microcytic hypochromic anemia, nervous injuries associated with convulsions, and vascular lesions resembling those of arteriosclerosis. 

In cats, pyridoxine deficiency is associated with the formation of calcium oxalate calculi in the kidneys. The magnesium and pyridoxine levels in the diet are related. Diets low in magnesium are responsible for increased incidence and severity of the oxalate lithiasis in the kidney, and the effect of the low-magnesium diet is counteracted by the administration of pyridoxine. These observations made in animals may have some relevance to the development of lithiasis in humans. Patients with recurring calcium oxalate stones in the kidney secrete more xanthurenic and pyridoxic acid than normal individuals, suggesting that lithiasis may result from deficient pyridoxine metabolism, possibly due to accelerated breakdown of the coenzyme. If other signs of pyridoxine deficiency develop, one must assume that the accelerated breakdown occurs only in a few organs, probably only in the kidneys. 

The observations made in oxaluric patients suggest that the lithiasis that pyridoxine-deficient cats develop might be related to the role that pyridoxine plays as a cofactor of the transaminase. Anemia developing in pyridoxine-deficient animals probably can be explained at least in part by an interference with heme synthesis. Indeed, heme synthesis is reduced to one-third of normal in reticulocyte-rich blood obtained from pyridoxine-deficient animals. The rate of heme synthesis reaches normal values when pyridoxal phosphate is added to the incubation medium. This effect... 

Y.L. Siow and K. Dakshinamurti. Effect of pyridoxine deficiency on aromatic amino acid decarboxylase in adult rat brain. Etqt. Brain Res. 59 575-581 (1985). 

S.K. Sharma and K. Dakshinamurti. Effects of serotonergic agents on plasma prolactin levels in pyridoxine-deficient adult male rats. Neurochem. Res. 19 687-692 (1994). 

More recently Wiss found that kynureninase inactivated by dialysis could be reactivated by pyridoxal-5-phosphate, but not by pyridoxal-2-phosphate. As pyridoxine deficiency has no observable effect on the conversion of hydroxyanthranilic acid to nicotinic acid, the action of this vitamin appears to be connected solely with the removal of the alanyl side chain at the kynurenine level. 

The recommended dose, 25 mg per kg body weight per day or less (= 1—2,5gm per day) should not be exceeded since in experimental animals and man a decrease or even reversal of the effect of the drug has been observed (Green et al. 1963). Furthermore, signs of pyridoxine deficiency could be produced in dogs treated with long-term administration of high doses of CPIB. 

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