The effect of aeds on the vitamin d metabolism is of considerable value especially in children. It has been suggested that the drugs such as phenytoin accelerate vitamin d metabolism or directly inhibit intestinal calcium absorption. Because 25ohd is the predominant circulating form of vitamin d in the normal population, it is considered to be the most reliable index. Phenytoin induced vitamin d deficiency presenting as. Phenytoin interferes with the renal activation of vitamin d. This may lead to vitamin d deficiency and heightened risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and hypophosphatemia in chronically. Dosage adjustment of vitamin d may be necessary when phenytoin is added to or withdrawn from concomitant therapy 195. Osteomalacia and phenytoin therapy annals of internal. The first step in the metabolism of vitamin d, 25 hydroxylation, occurs mainly in the liver 2. Warfarin may increase serum phenytoin concentrations. The chemical name is sodium 5,5diphenyl2, 4imidazolidinedione, having the following structural formula.
Inadequate low serum phenytoin levels could indicate inappropriate absorption, increased liver metabolism of the drug, renal disease, interaction with other medication etc. Enterohepatic circulation of vitamin d metabolites and their conjugates will be also discussed. The objective of this study was to determine the effect of antiepileptic drugs on vitamin d by measuring 25oh vitamin d levels in patients on aeds. In children, muscle weakness due to vitamin d deficiency is rarely.
Learn vocabulary, terms, and more with flashcards, games, and other study tools. It would be best to discuss the situation and the suggested management plan in detail with your treating neurologist. Influence of drugs on vitamin d and calcium metabolism. Significant decreases occurred in serum concentrations of calcium, albumin, and 25. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Significant decreases occurred in serum concentrations of calcium, albumin, and 25hydroxycholecalciferol. The effect of anti epileptic drug therapy on serum 25hydroxyvitamin. Musculoskeletal effects osteomalacia has been associated with phenytoin therapy and is considered to be due to phenytoin s interference with vitamin d metabolism see section 4. Severe hypocalcemia and resulting seizure caused by vitamin d. When the level is optimal, vitamin d should be reduced to a supplementation dose of 400800 iuday. Musculoskeletal effects osteomalacia has been associated with phenytoin therapy and is considered to be due to phenytoins interference with vitamin d metabolism see section 4. Phenytoin and other anticonvulsants that have been shown to induce the cyp450 enzyme are thought to affect bone mineral metabolism indirectly by increasing the metabolism of vitamin d3. Learn about side effects, warnings, dosage, and more. In vitamin d metabolism, antiepileptic drugs aeds, including phenytoin, are known to interact with cytochrome p450 activity.
The decreases in serum calcium paralleled those in serum albumin. Effect of antiepileptic drugs on bone density in ambulatory. It is possible that anticonvulsant drugs alter vitamin d metabolism which results in disturb ance of. Clinical pharmacokinetics of phenytoin springerlink. Phenytoin sodium is related to the barbiturates in chemical structure, but has a fivemembered ring.
Vitamin d vitamin d has been in the news frequently this past year, including an article in the new york times on november 16, 2009. Vitamin d rich foods and drinks include salmon or mackerel, canned tuna fish, and egg yolks as well as vitamin d fortified foods like cereals, juice, milk and other dairy products see charts at the bottom for detailed amounts per servings. Phenytoininduced changes in the bone mineral metabolism. There is also increasing awareness of endogenous, mostly steroid, pathways, relevant in particular to vitamin d and cholesterol metabolism, which are targets for this process. Cell differentiation inhibits proliferation and stimulates the normal differentiation of cells immunity the inactive form of vitamin d aids in the formation of active vitamin d which enhances immunity and inhibits the development of autoimmune disease. Pdf in the past, interactions between drugs and vitamin d have received only little or no. However, this medicine can make absence or petit mal seizures happen more frequently. Vitamin d has long been known for its effects on calcium and bone metabolism. Interplay between vitamin d and the drug metabolizing. Phenytoin may be prescribed with other seizure medications. Phenytoin can cause the platelet or white blood cell counts to drop, increasing the risk of bleeding or infection, respectively. Vitamin d is a fatsoluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. Deficiency of calcium, magnesium, or zinc may impair drug metabolism. Pdf calcium and bone metabolism in patients with epilepsy taking.
Vitamin d and fall riskgrand rounds presentation final. Consideration should be given to screening with bonerelated laboratory and radiological tests as appropriate and initiating treatment plans according to established guidelines. Phenytoin should be used with caution in patients with hypotension andor severe myocardial insufficiency. For vitamin d supplementation, vitamin d 3, the natural form of vitamin d, is preferred over vitamin d 2, because vitamin d 3 is most effective in maintaining adequate levels of vitamin d in the human body. Bikle1, 1va medical center, department of medicine and dermatology, university of california, san francisco, san francisco, ca 94121, usa correspondence. Nutrientdrug interactions nutritional disorders msd. Serum calcium, parathormone pth, 25hydroxyvitamin d 25. Bone mineral density, vitamin d and anticonvulsant therapy scielo. In 22 epileptic outpatients treated for at least 1 year with phenobarbitonephenytoin the local and total bone mass, together with serum and urinary indices of calcium metabolism, were measured before and during treatment with either vitamin d 2 or d 3, 4,000 iu daily for 24 weeks. Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in scandinavia. It is a medicine that has been approved by the food and drug administration to treat tonic clonic grand mal and complex partial seizures. The results showed a distinct difference in the action of the two vitamins on bone metabolism during. A guide to therapeutic drug monitoring melissa faye wu, bsc pharm. This can lead to a vitamin d deficiency, as well as low calcium and phosphate.
Several interactions are possible and the net effects are difficult to predict 106 195. Effect of phenytoin on bone and vitamin d metabolism. The rate of metabolism appears to be subject to genetic polymorphism. Phenytoin is mainly excreted in the urine as its parahydroxylated metabolite 23 to 70 percent, either free or in conjugated form 5 percent. Subjects who were already on aed, on drug therapy that interfere with vitamin d metabolism, those with hepatic, renal. Ligandbound vitamin d receptor binds to consensus sequences on target genes as a heterodimer with the retinoid x receptor and exerts transcriptional regulatory effects. Vitamin d fatsoluble vitamin hormonal regulation of. Vitamin c deficiency decreases activity of drugmetabolizing enzymes, especially in older people. This may enhance the metabolism of vitamin d and decrease vitamin d levels, which may lead to vitamin d deficiency, hypocalcemia, and hypophosphatemia. Therapy with phenytoin should be administered cautiously in patients with. Effect of phenytoin on bone and vitamin d metabolism wiley online. Increased metabolism of vitamin d, leading to low blood levels of 25hydroxyvitamin d, is seen in individuals given anticonvulsant medications and antituberculous therapy. Although several studies revealed that pht use was associated with low folate status, the exact mechanism underlying the effect of pht on homocysteine metabolism has not yet been clarified.
There are few clinicians who use prophylactic calcium or vitamin d for patients taking aed. Clinically important displacement can be caused by. Twothirds of the recruited subjects were vitamin d deficient. Cytochrome p450 3a4 cyp3a4 is a multifunctional enzyme involved in both xenobiotic and endobiotic metabolism. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin d synthesis. Low levels of biologically active vitamin d in patients on aeds have been demonstrated in a number of studies 33, 37, 4446, particularly with use of hepatic enzyme inducing medications like pb, pd, dph and cbz. Treatment for vitamin ddeficiency rickets requires therapeutic doses of calciferol.
Effects of phenytoin on serum levels of homocysteine. Phenytoin may also raise the serum glucose level in diabetic patients. Enzyme induction will continue for as long as the patient takes the inducer and no. In humans, only a small amount of 25ohd is metabolized in the kidney to other dihydroxy metabolites 3, 4. Dilantin phenytoin can cause vitamin d deficiency date june 11, 2014 author by eric christianson category osteoporosis, seizures dilantin phenytoin is probably one of the dirtiest drugs, but is necessary as it treats an obviously serious condition seizures. As the rate of administration increases, the plasma concentration at steady state. Comparative study of the relative influence of different. Vitamin d deficiency causes a lack of bone mineralization, which manifests as rickets in children and osteomalacia in adults. Phenytoin is metabolized by hepatic cytochrome p450 enzymes cyp2c9 and cyp2c19 and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. This medicine is available in different forms, including dilantin, phenytek, or generic phenytoin. Phenytoin is a relatively insoluble weak acid, usually administered as the sodium salt. Influence of drugs on vitamin d and calcium metabolism ncbi. Vitamin d is a well known fat soluble vitamin that is important for maintaining calcium and phosphate homeostasis, mineralization of the bone, and the modulation of gene expression, cell growth and differentiation.
Pdf influence of drugs on vitamin d and calcium metabolism. An international journal of medicine, volume 59, issue 3, june 1986, pages 569577. Calcium phosphate homeostasis mineral bone metabolism halfon m, phan o, teta d. Phenytoin therapy in young male patients for 1year causes a bone loss at femur and spine in the absence of vitamin d deficiency and significant bone loss in the cortical bone radius. Previous research showed that phenytoin, as enzyme inducers, can directly regulate the activity of different liver enzymes. This effect has been attributed to metabolism of vitamin d to polar inactive metabolites by the hepatic microsomes. Alterations in calcium, vitamin d and bone tissue metabolism have been associated with the following drugs. Dilantin phenytoin can cause vitamin d deficiency med. Nutrientdrug interactions and nutritional disorders learn about from the msd manuals medical professional version. Callaghan, a comparative study of the relative influence of different anticonvulsant drugs, uv exposure and diet on vitamin d and calcium metabolism in outpatients with epilepsy, qjm. The drug has a moderately large volume of distribution and is approximately 90% bound to plasma proteins. The older aeds are phenobarbital pb, phenytoin pht, carbamazepine cbz, primidone prm, sodium. Vitamin d 3, is not a vitamin its a hormone but its easier and safer to say vitamin. The active hormone, 1,25dihydroxyvitamin d, exerts its effects by binding to the vitamin d receptor, a member of the steroidthyroid hormone superfamily of nuclear receptors.
Serum 25oh vitamin d level testing should be repeated in 3 months after giving pharmacologic doses of vitamin d. Drugs that activate the pregnane x receptor can disrupt vitamin d metabolism. Calcium and vitamin d metabolism were evaluated in 5 adult epileptic patients before and during treatment with phenytoin. Because it interferes with vitamin d metabolism, phenytoin can cause weakening of the bones osteomalacia. Sunarc sun exposure uvb protects against 16 types of cancer the new study links uvb as protective to a total of 16 types of cancer, primarily epithelial pertaining to the surface cancers of the digestive and reproductive systems. Phenytoin 100mg filmcoated tablets summary of product. Each dilantin 100 mg extended oral capsulecontains 100 mg phenytoin sodium. Osteomalacia has been associated with phenytoin therapy and is considered to be due to phenytoins interference with vitamin d metabolism.
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