Vitamin d deficiency can result in lower bone mineral density and an increased risk of reduced bone density osteoporosis or bone fracture because a lack of vitamin d alters mineral metabolism in the body. Serum calcium, parathormone pth, 25hydroxyvitamin d 25ohd3, osteocalcin. Chronic hypercalcemia may lead to serious or even lifethreatening complications, and. It also plays an important role in maintaining proper bone structure. Side effects requiring immediate medical attention. We prospectively studied 36 young males aged 2030 years, with newonset epilepsy, and treated with phenytoin. Effect of phenytoin on bone and vitamin d metabolism. Effect of vitamin d and calcium supplementation on bone. The older aeds are phenobarbital pb, phenytoin pht, carbamazepine cbz, primidone. Significant decreases occurred in serum concentrations of calcium, albumin, and 25hydroxycholecalciferol. 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.
Effect of antiepileptic drugs on bone density in ambulatory. The effect of anti epileptic drug therapy on serum 25hydroxyvitamin. The results showed a distinct difference in the action of the two vitamins on bone metabolism during anticonvulsant. Significant decreases occurred in serum concentrations of calcium, albumin, and 25. The t3 and t4 thyroid hormones control the bone metabolism and the mineral homeosthasis of adults22 and the. Vitamin d is a group of fatsoluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and multiple other biological effects. Dec 11, 2018 dilantin phenytoin sodium injection, usp is a sterile solution of 50 mg phenytoin sodium per milliliter for intravenous or intramuscular administration. Beside this, the medication oriented supplementation of vitamin d can ameliorate the pharmacologic action of some drugs, such as bisphosphonates, cytostatics and statins.
Although not all of these side effects may occur, if they do occur they may need medical attention. The objective of the study was to determine the bone loss and change in bone mineral parameters in patients treated with phenytoin sodium. Antiepileptic drugs aeds have an adverse effect on the bone mineral metabolism. Data on bone specific effects of newer aeds are limited. Its available as a generic drug and as the brandname drugs phenytek and dilantin. This may lead to vitamin d deficiency and heightened risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and. G influence of drugs on vitamin d and calcium metabolism. It has many clinical quirks that you need to be aware of. Oct 23, 2014 vitamin d regulates the plasma levels of calcium and phosphorous plasma calcium levels are regulated by effects of 1,25 dhcc on small intestine, kidney and bone it maintains the plasma calcium levels by increasing absorption of calcium from small intestine, increasing reabsorption of calcium by renal distal tubules and increasing. Vitamin d is required for the regulation of the minerals calcium and phosphorus found in the body.
Low dose phenytoin is an osteogenic agent in the rat. It is important in promoting absorption of calciumphosphorus in the gut to support bone integrity. Because it interferes with vitamin d metabolism, phenytoin can cause weakening of the bones. This may enhance the metabolism of vitamin d and decrease vitamin d levels, which may lead to vitamin d deficiency. A 29yearold lady came for evaluation of metabolic bone disease. Effects of phenytoin dph on parathyroid hormone pth and 1,25dihydroxyvitamin d 3 1,25dhccmediated bone resorption in bone organ culture were evaluated. Vitamin d and bone metabolism balanced system low levels of vitamin d calcium absorption meet slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. To assess the status of vitamin d and the effects of calcium and vitamin d3 supplementation on the bone metabolism in a group of adults with downs syndrome ds. Vitamin d metabolism, mechanism of action, and clinical. However, pth tended to overcome the initial effects of dph, whereas bone resorption due to 1,25dhcc remained depressed as if dph treatment had. 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.
Dilantin phenytoin can cause vitamin d deficiency med. Anticonvulsants, osteomalacia, osteoporosis, vitamin d. Uses, side effects, interactions, dosage, and warning. Scientific evidence suggests that 25oh d serum levels should be over 75 nmoll. The solution is in a vehicle containing 40% propylene glycol and 10% alcohol in water for injection, adjusted to ph 12 with sodium hydroxide. Due to its large surface area, the small intestine is the main site of phenytoin absorption. The aim of the present study was to evaluate the possibility that low doses of phenytoin are osteogenic in vivo by measuring the effects of phenytoin administration on serum and bone histomorphometric parameters of bone. 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.
The production of vitamin d 3 d 3 in the skin is not an enzymatic process. Longterm use of phenytoin for the treatment of epilepsy has been associated with increased thickness of craniofacial bones. Phenytoin monotherapy in patients with epilepsy affects calcium metabolism and bone turnover markers leading to hypovitaminosis d, hypocalcemia, reduced bone mineral density and its imminent. Jun 27, 2019 however, phenytoin has been shown to induce the cyp450 enzyme, which can affect bone mineral metabolism indirectly by increasing the metabolism of vitamin d3. Different actions of vitamin d 2 and d 3 on bone metabolism. Multiple sclerosis and vitamin d what is vitamin d. Phenytoin sodium is related to the barbiturates in chemical structure, but has a fivemembered ring. Thus, vitamin d is also critical for bone remodeling through its role as a potent stimulator of bone resorption. The mechanism for phenytoin dilantin associated decreases in vitamin d. Data sources include ibm watson micromedex updated 4 may 2020, cerner multum updated 4 may.
Antiepileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome p450 and other enzyme, which may lead to catabolism of vitamin d and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. Dilantin extended oral capsules phenytoin pfizer medical. Vitamin d toxicity can result from regular excess intake of this vitamin, and may lead to hypercalcemia and excess bone loss. In 2011, the endocrine society issued clinical practice guidelines for vitamin d, stating that the desirable serum concentration of 25oh d is 75 nmoll 30 ngml to maximize the effect of this vitamin on calcium, bone, and muscle metabolism. The objective is to determine the effect of aed on vitamin d levels and bone density in ambulatory patients and to compare the effects of enzymeinducing. Phenytoin should be used with caution in patients with hypotension andor severe myocardial insufficiency.
Dec 10, 2018 phenytoin sodium injection, usp is a sterile solution containing in each ml phenytoin sodium 50 mg, propylene glycol 0. Phenytoin sodium injection, usp is a sterile solution containing in each ml phenytoin sodium 50 mg, propylene glycol 0. Pdf calcium and bone metabolism in patients with epilepsy taking. Phenytoin induces hepatic metabolizing enzymes, which may enhance metabolism of vitamin d and decrease vitamin d levels, leading to vitamin d deficiency, hypocalcemia, and hypophosphatemia. Calcium and vitamin d metabolism were evaluated in 5 adult epileptic patients. Vitamin d regulates the plasma levels of calcium and phosphorous plasma calcium levels are regulated by effects of 1,25 dhcc on small intestine, kidney and bone it maintains the plasma calcium levels by increasing absorption of calcium from small intestine, increasing reabsorption of calcium by renal distal tubules and increasing. The aim of the present study was to evaluate the possibility that low doses of phenytoin are osteogenic in vivo by measuring the effects of phenytoin administration on serum and bone histomorphometric parameters of bone formation in two rat experiments. In 22 epileptic outpatients treated for at least 1 year with phenobarbitone phenytoin the local and total bone mass, together with serum and urinary indices of calcium metabolism, were measured before and during treatment with either vitamin d2 or d3, 4,000 iu daily for 24 weeks. Individuals at particular risk include those with hyperparathyroidism, kidney disease, sarcoidosis, tuberculosis, or histoplasmosis.
Epilepsy, prolonged phenytoin usage, and its effects on bone. Effect of phenytoin on bone and vitamin d metabolism core. Sorry, we are unable to provide the full text but you may find it at the following locations. The decreases in serum calcium paralleled those in serum albumin. Prophylactic administration of adequate amounts of calcium and vitamin d is recommended for all patients.
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. Effect of phenytoin on rat bone resorption in vitro. Difusion effect of phenytoin on bone and vitamin d metabolism. The biologically active metabolite of vitamin d, 1,25oh 2 d 3, affects mineral homeostasis and has numerous other diverse physiological functions including effects on growth of cancer cells and protection against certain immune disorders. Phenytoininduced changes in the bone mineral metabolism in.
Vitamin d metabolism the major biologically active metabolite of vitamin d is 1,25 dihydroxy vitamin d, which, in addition to its roles in bone metabolism, has antiproliferative, prodifferentiation and immunosuppressive effects. Severe vitamin d deficiency results in defective mineralisation osteomalacia, or rickets in the developing skeleton. In 2011, the endocrine society issued clinical practice guidelines for vitamin d, stating that the desirable serum concentration of 25ohd is 75 nmoll 30 ngml to maximize the effect of this vitamin on calcium, bone, and muscle metabolism. Antiepileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome p450 and other enzyme, which may lead to catabolism of vitamin d and hypocalcemia and other effects that may significantly effect the risk for low bone mass and. Theoretically it can be worthwhile to supplement calcium and vitamin d even before initiation of antiepileptic therapy. Influence of drugs on vitamin d and calcium metabolism. Several drugs can interfere with the vitamin d and bone metabolism. There are few clinicians who use prophylactic calcium or vitamin d for patients taking aed. Dilantin phenytoin is probably one of the dirtiest drugs, but is necessary as it treats an obviously serious condition seizures. It also reported that to consistently raise serum levels of 25oh d above 75 nmoll 30 ngml, at.
The chronic use of phenytoin in patients with epilepsy has been associated with decreased bone mineral density osteopenia, osteoporosis, and osteomalacia and bone fractures. Scientific evidence suggests that 25ohd serum levels should be over 75 nmoll. Phenytoin induced osteopathy too common to be neglected. However, pth tended to overcome the initial effects of dph, whereas bone resorption due to 1,25dhcc remained depressed as if dph treatment had continued. The possible explanations for these unexpected findings are discussed. Levetiracetam phenytoinvalproatebonemineralcontentbiomechanical strength. The results showed a distinct difference in the action of the two. At the end of 6 months, the metabolic bone disease profile and serum levels of. Vitamin d has long been known for its effects on calcium and bone metabolism. Phenytoin can cause the platelet or white blood cell counts to drop, increasing the risk of bleeding or infection, respectively. Phenytoininduced changes in the bone mineral metabolism. The effect of aeds on the vitamin d metabolism is of considerable value especially in children. Effect of chronic metabolic acidosis on vitamin d metabolism.
Direct effect of the drug on intestinal calcium transport includes other mechanisms of aed induced bone loss. Influence of drugs on vitamin d and calcium metabolism ncbi. Longterm antiepileptic drug aed use causes multiple abnormalities in calcium and bone metabolism that have been most extensively described in institutionalized patients. The mechanism for phenytoin dilantin associated decreases. It also reported that to consistently raise serum levels of 25ohd above 75 nmoll 30 ngml, at. Phenytoin may be given intravenously to patients who cannot receive the drug orally or who require rapid onset of drug effect. They are thought to affect bone and mineral metabolism indirectly by increasing the metabolism of vitamin d, thereby causing vitamin d insufficiency or. Phenytoin 100mg filmcoated tablets summary of product. Dxa should be done in patients during the treatment with aeds to identify patients who are susceptible to increased risk of fractures. Phenytoin induced osteopathy too common to be neglected ncbi.
For maintenance of aromatase activity necessary in osteoblasts, physiological levels of vitamin d3 are required. The effect of anti epileptic drug therapy on serum 25. 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. D 3 cholecalciferol is produced from 7dehydrocholesterol 7dhc through a twostep process in which the b ring is broken by uv light spectrum 280320 uvb radiation from the sun, forming pred 3 that isomerizes to d 3 in a thermosensitive but noncatalytic process. Because it interferes with vitamin d metabolism, phenytoin can cause weakening of the bones osteomalacia. Drugs such as cbz, pb, prm and dph are known to induce hepatic mixed function oxidase activity throughout the microsomal enzymes p450 in the liver. The protocol was approved by the committee on human studies and signed informed consent was obtained from all participants. Levetiracetam, phenytoin, and valproate act differently on. In humans, the most important compounds in this group are vitamin d 3 also known as cholecalciferol and vitamin d 2 ergocalciferol the major natural source of the vitamin is synthesis of cholecalciferol in the. Phenytoin oral capsule is used to treat tonicclonic and complex partial seizures in people with epilepsy.
Effects of phenytoin andor vitamin k2 menatetrenone on bone mineral density in the tibiae of growing rats article in life sciences 70. The objective is to determine the effect of aed on vitamin d levels and bone density in ambulatory patients and to compare the effects of enzymeinducing and. Effects of phenytoin andor vitamin k2 menatetrenone on. Effect of phenytoin on bone and vitamin d metabolism bell. Along with its needed effects, phenytoin may cause some unwanted effects. Phenytoin is poorly soluble in water and is therefore commonly given as phenytoin sodium salt, which dissolves more readily. This may lead to vitamin d deficiency and heightened risk of osteomalacia, bone fractures, osteoporosis, hypocalcemia, and hypophosphatemia in chronically treated epileptic patients. Dec 14, 2005 to assess the status of vitamin d and the effects of calcium and vitamin d3 supplementation on the bone metabolism in a group of adults with downs syndrome ds. Anticonvulsant drugs and bone disease in the elderly. Other important side effects caused by phenytoin include sexual dysfunction. Hypocalcemia, folate deficiency, abnormal vitamin d metabolism, increased vitamin d requirements possibly resulting from abnormal vitamin d metabolism, vitamin k deficiency, hypophosphatemia. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Consequently, in the hypogonadism, smaller formation of the linking calcium protein decreasing its intestinal absorption is observed21.
Effect of phenytoin on bone and vitamin d metabolism wiley online. Chronic phenytoin use has been associated with decreased bone density and increased bone fractures. Effect of metabolic acidosis on vitamin d metabolism 645 disease, bone disease, or nephrolithiasis, or were they receiving a medication known to affect vitamin d metabolism. This leads to increased metabolism of vitamin d, thus decreased vitamin d levels. Phenytoin induces metabolizing enzymes in the liver.
Introduction vitamin d has long been known for its effects on calcium and bone metabolism. Phenytoin can potentially injure the liver although this is an uncommon occurrence. Phenytoin interferes with the renal activation of vitamin d. Vitamin d is synthesized by the skin from sunlight.
Anticonvulsants have the broad spectrum of side effects on the bone that are collectively. Normal bone metabolism is the complex sequence of bone turnover osteoclastogenesis and bone formation osteoblastogenesis physiology of bone metabolism. The effect of phenytoin monotherapy on serum 25hydroxyvitamin d and bone health markersa prospective study. Pdf the effect of phenytoin monotherapy on serum 25. The objective is to determine the effect of aed on vitamin d levels and bone density in ambulatory patients and to compare the effects of enzymeinducing and noninducing aed and of single vs multiple therapy on. Oxcarbazepine has fewer side effects on calcium and bone metabolism than. 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. Calcium and vitamin d metabolism were evaluated in 5 adult epileptic patients before and during treatment with phenytoin. Vitamin d deficiency, as well as low calcium and phosphate in the blood cause decreased bone mineral density. Calcium and bone metabolism in patients with epilepsy taking phenytoin or. These findings warrant further human studies of possible adverse effects of lev on bone development and growth, particularlyinchildrenandadolescents. Effect of the physical activity on normal bone and on the. Therefore, the higher vitamin d cutoffs of 30 ngml have not been the official recommendation of the american academy of pediatrics, pes, or their european counterparts.
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