Pyridoxine levodopa

Levodopa interacts with many different drugs. When levodopa is used with phenytoin, reserpine, and papaverine, there is a decrease in response to levodopa The risk of a hypertensive crisis increases when levodopa is used with the monoamine oxidase inhibitors (see Chap. 31). Foods high in pyridoxine (vitamin B6) or vitamin B6 preparations reverse the effect of levodopa However, when carbidopa is used with levodopa, pyridoxine has no effect on the action of levodopa hi fact, when levodopa and carbidopa are given together, pyridoxine may be prescribed to decrease the adverse effects associated with levodopa... 

If your patient with parkinsonism is taking levodopa, he must be careful to avoid vitamin B6 (pyridoxine) because it may interfere with the therapeutic effects of the drug. Most multivitamin supplements contain vitamin B6. Therefore, be sure to instruct your patient to check with his health care provider before taking any vitamin supplements. 

Levodopa is converted to dopamine in the peripheral tissues by dopa decarboxylase, which has pyridoxine as a cofactor. Excess of this vitamin will increase this reaction, which is an undesirable effect because dopamine does not cross the blood-brain barrier where the therapeutic effect is desired. 

Pyridoxine [Vitamin B ] [Vitamin B Supplement] U e Rx prevention of vit B6 deficiency Action Vit supl Dose Adults. Deficiency 10-20 mg/d PO Drug-induced neuritis 100-200 mg/d 25-100 mg/d prophylaxis Peds. 5-25 mg/d x 3 wk Caution [A (C if doses exceed RDA), +] Contra Component aUCTgy Disp Tabs 25, 50, 100 mg inj 100 mg/mL SE Allergic Rxns, HA, N Interactions -1- Effects OF levodopa, phenobarbital, phenytoin EMS Can be used as an antidote for isoniazid poisoning OD May cause sensory nerve damage (numbness, tingling, reduced sensation) and coordination problems Sxs are usually revised aft stopping pyridoxine symptomatic and supportive... 

Pharmacologic doses of pyridoxine (vitamin B6 ) enhance the extracerebral metabolism of levodopa and may therefore prevent its therapeutic effect unless a peripheral decarboxylase inhibitor is also taken. Levodopa should not be given to patients taking monoamine oxidase A inhibitors or within 2 weeks of their discontinuance because such a combination can lead to hypertensive crises. 

Interactions The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness (Figure 8.6). Concomitant administration of levodopa and monoamine oxidase (MAO) inhibitors, such as phenelzine (see p. 124), can produce a hypertensive crisis caused by enhanced catecholamine production therefore, caution is required when they are used simultaneously. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central amines. In patients with glaucoma, the drug can cause an increase in intraocular pressure. Cardiac patients should be carefully monitored because of the possible development of cardiac arrhythmias. Antipsychotic drugs are contraindicated in parkinsonian patients, since these block dopamine receptors and produce a parkinsonian syndrome themselves. 

Dopa-decarboxylase is a pyridoxine-dependent enzyme and concomitant use of pyridoxine, e.g. in self-medication with a multivitamin preparation, can enhance peripheral conversion of levodopa to dopamine so that less is available to enter the CNS, and benefit is lost. This effect does not occur, of course, with the now usual levodopa-decarboxylase inhibitor combinations. 

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. 

Leon AS, Spiegel HE, Thomas G, Abrams WB. Pyridoxine antagonism of levodopa in parkinsonism. JAMA 1971 218(13) 1924-7. 

Pyridoxine has both dopamine-enhancing and dopamineblocking properties on the one hand pyridoxine (like dopamine) depresses the release of prolactin from the pituitary gland on the other hand, in oral doses of 10-20 mg it rapidly reverses the therapeutic effect of dopamine (16). This should be borne in mind if pyridoxine is prescribed for nursing mothers or for patients treated with levodopa for Parkinson s disease or syndrome, although the problem does not seem to arise when using the combination of levodopa with decarboxylase inhibitors. 

Vitamin B complex is the collective term for a number of water-soluble vitamins found particularly in dairy products, cereals and liver.Vitamin B (thiamine) is used by mouth for dietary supplement purposes and by injection in emergency treatment of Wernicke-Korsakoff syndrome. Vitamin B2 (riboflavin) is a constituent of the coenzyme FAD (flavine adenine dinucleotide) and FMN (flavine mononucleotide) and is therefore important in cellular respiration. Vitamin Be (pyridoxine) is a coenzyme for decarboxylases and transamination, and is concerned with many metabolic processes. Overdose causes peripheral neuropathy. It may be used medically for vomiting and radiation sickness and for premenstrual tension. Pyridoxine has a negative interaction with the therapeutic use of levodopa in parkinsonism by enhancing levodopa decarboxylation to dopamine in the periphery, which does not then reach the brain. The antitubercular drug isoniazid interferes with pyridoxine, and causes a deficiency leading to peripheral neuritis that may need to be corrected with dietary supplements. Vitamin B ... 

Interestingly, pyridoxine is known to antagonize levodopa , perhaps by promoting possible premature decarboxylation (as a coenzyme to dopa decarboxylase) before the drug has gained entry into the brain. It has been observed that carbidopa curtails antagonism by pyridoxine to a certain extent. 

Note Patients must not take multivitamin supplements containing pyridoxine during the course of levodopa therapy. L... 

Pyridoxine (a coenzyme for dopa decarboxylase) can reverse the therapeutic effects of levodopa by increasing decarboxylase activity, which results in more levodopa being converted to dopamine in the periphery and, consequently, less being available for penetration into the CNS. When peripheral dopa decarboxylation is blocked with carbidopa, however, the pyridoxine effect on peripheral levodopa metabolism is negligible (Fig. 25.7). 

The effects of levodopa are reduced or abolished by pyridoxine, but this interaction does not occur when ievodopa is given with the dopa-decarboxyiase inhibitors carbidopa or benserazide, as is usuai ciinicai practice. 

A study in 25 patients taking levodopa alone found that if they were given high doses of pyridoxine (750 to 1000 mg daily), the efteets of the levodopa were redueed within 24 hours, and were eompletely abolished within 3 to 4 days. Daily doses of pyridoxine 50 to 100 mg also reduced or abolished the effects of levodopa, and an increase in the signs and symptoms of parkinsonism occurred in 8 out of 10 patients taking only 5 to 10 mg of pyridoxine daily. ... 

The antagonism of the effects of levodopa (given without a dopa-decar-boxylase inhibitor) by pyridoxine has been described in numerous other reports. " ... 

The conversion of levodopa to dopamine within the body requires the presence of pyridoxal-5-phosphate (derived from pyridoxine) as a co-factor. When dietary amounts of pyridoxine are high, the peripheral metabolism of levodopa by dopa-decarboxylase is increased so that less is available for entry into the CNS, and its effects are reduced accordingly. Pyridoxine may also alter levodopa metabolism by Schiff-base formation. However, in the presence of dopa-decarboxylase inhibitors such as carbidopa or benserazide, this peripheral metabolism of levodopa is reduced and much larger amounts are available for entry into the CNS, even if quite small doses are given. So even in the presence of large amounts of pyridoxine, the peripheral metabolism remains unaffected and the serum levels of levodopa are virtually unaltered. 

Cotzias GC, PapavasiliouPS. Blocking the negative effects of pyridoxine on patients receiving levodopa. JAMA (1971) 215,1504-5. 

Abnormal involuntary movements frequently accompany optimal improvement with levodopa. The duration and the dose are related to the occurrence of these movements so that up to 73% of patients have them after 12 months of treatment. Abnormalities are seen earliest in the head and mouth, then later in the limbs and trunk, sometimes becoming violent and severe. Usually they can be reversed by lowering the levodopa dose or by adding other drugs (phenothiazines, haloperidol or pyridoxine) but with both approaches some therapeutic benefit is often lost. 

Pyridoxine (given alone or in combination with vitamin Bn ) may induce a deterioration of an acne vulgaris or an eruption of an acneiform exanthema (22 ). The antagonism between pyndoxine and levodopa is well known. The matter should be borne in mind when prescribing pyAdoxine for patients treated with levodopa for Parkinson s disease or syndrome (23 ). 

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