Efecto de los medicamentos antiepilépticos en el metabolismo de la vitamina D y el impacto negativo relacionado al déficit

  • Juan J. Ramírez-Jiménez Hospital San Vicente Fundación
  • Juan M. Alfaro-Velásquez Universidad de Antioquia
Palabras clave: deficiencia de vitamina D, vitamina D, sistema enzimático del citocromo P-450, receptores de calcitriol, anticonvulsivantes, osteopatía.

Resumen

La alteración en el metabolismo de la vitamina D ha ido creciendo en importancia hasta considerarse un problema de salud pública. Cada vez son más frecuentes las etiologías relacionadas al déficit de la vitamina D y con consecuencias a largo plazo, lo que hace necesario conocer no sólo las bases moleculares del metabolismo de la vitamina D, con especial atención en la participación de las enzimas de la familia del citocromo P450, sino la descripción de las vías metabólicas, la interacción con el receptor específico, las acciones genómicas y no genómicas, sus resultados en el metabolismo óseo y las acciones extra esqueléticas. Además, la acción directa de los antiepilépticos sobre las enzimas de la citocromo P450 y su efecto negativo sobre los niveles de la vitamina D y el metabolismo óseo. Esta revisión pretende brindar las bases que permitan extrapolar estos conceptos a la práctica clínica e identificar los pacientes con riesgo de hipovitaminosis D debido al uso crónico de antiepilépticos que requieren una conducta terapéutica. Es necesario tener presente que en la actualidad no hay un protocolo clínico universal sobre el seguimiento de estos pacientes incluso con la mejoría en el acceso a recursos diagnósticos.

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Biografía del autor/a

Juan J. Ramírez-Jiménez, Hospital San Vicente Fundación

Médico Pediatra. Residente de Endocrinología Pediátrica, Universidad de Antioquia-Hospital Universitario San Vicente Fundación (HUSVF). Medellín, Colombia. 

Juan M. Alfaro-Velásquez, Universidad de Antioquia

Médico Pediatra Endocrinólogo. Director Departamento de Endocrinología Pediátrica, Universidad de Antioquia. Medellín, Colombia.

Referencias bibliográficas

Offermann G, Pinto V, Kruse R. Antiepileptic drugs and vitamin D supplementation. Epilepsia 1979; 20: 3-15.

https://doi.org/10.1111/j.1528-1157.1979.tb04771.x

El-Hajj Fuleihan G, Dib L, Yamout B, Sawaya R, Mikati MA. Predictors of bone density in ambulatory patients on antiepileptic drugs. Bone 2008; 43: 149-155.

https://doi.org/10.1016/j.bone.2008.03.002

Souverein PC, Webb DJ, Petri H, Weil J, Van Staa TP, Egberts T. Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database. Epilepsia 2005; 46: 304-310.

https://doi.org/10.1111/j.0013-9580.2005.23804.x

Shellhaas RA, Joshi SM. Vitamin D and bone health among children with epilepsy. Pediatr Neurol 2010; 42: 385-393.

https://doi.org/10.1016/j.pediatrneurol.2009.12.005

Valmadrid C, Voorhees C, Litt B, Schneyer CR. Practice patterns of neurologists regarding bone and mineral effects of antiepileptic drug therapy. Arch Neurol 2001; 58: 1369-1374.

https://doi.org/10.1001/archneur.58.9.1369

Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Lewiecki EM, et al. Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference. J Clin Densitom 2008; 11: 75-91.

https://doi.org/10.1016/j.jocd.2007.12.007

Ranganathan LN, Ramaratnam S. Vitamins for epilepsy. Cochrane Database Syst Rev 2005: CD004304.

https://doi.org/10.1002/14651858.CD004304.pub2

Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 2008; 122: 1142-1152.

https://doi.org/10.1542/peds.2008-1862

Harijan P, Khan A, Hussain N. Vitamin D deficiency in children with epilepsy: Do we need to detect and treat it? J Pediatr Neurosci 2013; 8: 5-10.

https://doi.org/10.4103/1817-1745.111413

Mikati MA, Dib L, Yamout B, Sawaya R, Rahi AC, Fuleihan Gel H. Two randomized vitamin D trials in ambulatory patients on anticonvulsants: impact on bone. Neurology 2006; 67: 2005-2014.

https://doi.org/10.1212/01.wnl.0000247107.54562.0e

Chung S, Ahn C. Effects of anti-epileptic drug therapy on bone mineral density in ambulatory epileptic children. Brain Dev 1994; 16: 382-385.

https://doi.org/10.1016/0387-7604(94)90125-2

Gniatkowska-Nowakowska A. Fractures in epilepsy children. Seizure 2010; 19: 324-325.

https://doi.org/10.1016/j.seizure.2010.04.013

Oner N, Kaya M, Karasalihoglu S, Karaca H, Celtik C, Tutunculer F. Bone mineral metabolism changes in epileptic children receiving valproic acid. J Paediatr Child Health 2004; 40: 470-473.

https://doi.org/10.1111/j.1440-1754.2004.00431.x

Shellhaas RA, Barks AK, Joshi SM. Prevalence and risk factors for vitamin D insufficiency among children with epilepsy. Pediatr Neurol 2010; 42: 422-426.

https://doi.org/10.1016/j.pediatrneurol.2010.03.004

Holick MF. Vitamin D: extraskeletal health. Endocrinol Metab Clin North Am 2010; 39: 381-400, table of contents.

https://doi.org/10.1016/j.ecl.2010.02.016

Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML. Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics 2009; 124: e362-370.

https://doi.org/10.1542/peds.2009-0051

Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res 2011; 31: 48-54.

https://doi.org/10.1016/j.nutres.2010.12.001

Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab 2010; 95: 471-478.

https://doi.org/10.1210/jc.2009-1773

Zuluaga Espinosa NA, Alfaro Velásquez JM, Balthazar González V, Jiménez Blanco KE, Campuzano Maya G. Vitamina D: nuevos paradigmas. Medicina & laboratorio 2011; 17: 211-246.

Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 2008; 88: 491S-499S.

https://doi.org/10.1093/ajcn/88.2.491S

Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ. Vitamin D: metabolism. Endocrinol Metab Clin North Am 2010; 39: 243-253.

https://doi.org/10.1016/j.ecl.2010.02.002

Miller WL. The syndrome of 17,20 lyase deficiency. J Clin Endocrinol Metab 2012; 97: 59-67.

https://doi.org/10.1210/jc.2011-2161

Reichrath J, Lehmann B, Carlberg C, Varani J, Zouboulis CC. Vitamins as hormones. Horm Metab Res 2007; 39: 71-84.

https://doi.org/10.1055/s-2007-958715

Schuster I. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim Biophys Acta, Proteins Proteomics 2011; 1814: 186-199.

https://doi.org/10.1016/j.bbapap.2010.06.022

Shinkyo R, Sakaki T, Kamakura M, Ohta M, Inouye K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem Biophys Res Commun 2004; 324: 451-457.

https://doi.org/10.1016/j.bbrc.2004.09.073

Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem 2003; 278: 38084-38093.

https://doi.org/10.1074/jbc.M307028200

Le Carrour T, Assou S, Tondeur S, Lhermitte L, Lamb N, Reme T, et al. Amazonia!: An Online Resource to Google and Visualize Public Human whole Genome Expression Data. Open Bioinforma J 2010; 4: 5-10.

https://doi.org/10.2174/1875036201004010005

Sawada N, Sakaki T, Kitanaka S, Kato S, Inouye K. Structure-function analysis of CYP27B1 and CYP27A1. Studies on mutants from patients with vitamin D-dependent rickets type I (VDDR-I) and cerebrotendinous xanthomatosis (CTX). Eur J Biochem 2001; 268: 6607-6615.

https://doi.org/10.1046/j.0014-2956.2001.02615.x

Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol 2008; 181: 7090-7099.

https://doi.org/10.4049/jimmunol.181.10.7090

White JH. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect Immun 2008; 76: 3837-3843.

https://doi.org/10.1128/IAI.00353-08

Schuster I, Egger H, Astecker N, Herzig G, Schussler M, Vorisek G. Selective inhibitors of CYP24: mechanistic tools to explore vitamin D metabolism in human keratinocytes. Steroids 2001; 66: 451-462.

https://doi.org/10.1016/S0039-128X(00)00166-5

Schuessler M, Astecker N, Herzig G, Vorisek G, Schuster I. Skin is an autonomous organ in synthesis, two-step activation and degradation of vitamin D(3): CYP27 in epidermis completes the set of essential vitamin D(3)-hydroxylases. Steroids 2001; 66: 399-408.

https://doi.org/10.1016/S0039-128X(00)00229-4

van Etten E, Stoffels K, Gysemans C, Mathieu C, Overbergh L. Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev 2008; 66: S125-134.

https://doi.org/10.1111/j.1753-4887.2008.00096.x

Adams JS, Hewison M. Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase. Arch Biochem Biophys 2012; 523: 95-102.

https://doi.org/10.1016/j.abb.2012.02.016

Prosser DE, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci 2004; 29: 664-673.

https://doi.org/10.1016/j.tibs.2004.10.005

Masuda S, Byford V, Arabian A, Sakai Y, Demay MB, St-Arnaud R, et al. Altered pharmacokinetics of 1alpha,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 in the blood and tissues of the 25-hydroxyvitamin D-24-hydroxylase (Cyp24a1) null mouse. Endocrinology 2005; 146: 825-834.

https://doi.org/10.1210/en.2004-1116

Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 2008; 29: 726-776.

https://doi.org/10.1210/er.2008-0004

Pike JW, Meyer MB, Watanuki M, Kim S, Zella LA, Fretz JA, et al. Perspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its receptor. J Steroid Biochem Mol Biol 2007; 103: 389-395.

https://doi.org/10.1016/j.jsbmb.2006.12.050

Audi L, Marti G, Esteban C, Oyarzabal M, Chueca M, Gussinye M, et al. VDR gene polymorphism at exon 2 start codon (FokI) may have influenced Type 1 diabetes mellitus susceptibility in two Spanish populations. Diabet Med 2004; 21: 393-394.

https://doi.org/10.1111/j.1464-5491.2004.01126.x

Petty SJ, Paton LM, O'Brien TJ, Makovey J, Erbas B, Sambrook P, et al. Effect of antiepileptic medication on bone mineral measures. Neurology 2005; 65: 1358-1365.

https://doi.org/10.1212/01.wnl.0000180910.72487.18

Khanna S, Pillai KK, Vohora D. Insights into liaison between antiepileptic drugs and bone. Drug Discov Today 2009; 14: 428-435.

https://doi.org/10.1016/j.drudis.2009.01.004

Pascussi JM, Robert A, Nguyen M, Walrant-Debray O, Garabedian M, Martin P, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest 2005; 115: 177-186.

https://doi.org/10.1172/JCI21867

St-Arnaud R, Arabian A, Travers R, Barletta F, Raval-Pandya M, Chapin K, et al. Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology 2000; 141: 2658-2666.

https://doi.org/10.1210/endo.141.7.7579

Takasu H, Sugita A, Uchiyama Y, Katagiri N, Okazaki M, Ogata E, et al. c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs. J Clin Invest 2006; 116: 528-535.

https://doi.org/10.1172/JCI24742

Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking DJ. The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone 2004; 35: 312-319.

https://doi.org/10.1016/j.bone.2004.02.003

Fox SW, Lovibond AC. Current insights into the role of transforming growth factor-beta in bone resorption. Mol Cell Endocrinol 2005; 243: 19-26.

https://doi.org/10.1016/j.mce.2005.09.008

Pack AM. The Association Between Antiepileptic Drugs and Bone Disease. Epilepsy Curr 2003; 3: 91-95.

https://doi.org/10.1046/j.1535-7597.2003.03306.x

Qin H, Yang FS. Calcitonin may be a useful therapeutic agent for osteoclastogenesis syndromes involving premature eruption of the tooth. Med Hypotheses 2008; 70: 1048-1050.

https://doi.org/10.1016/j.mehy.2007.08.024

Shearer MJ. Vitamin K. Lancet 1995; 345: 229-234.

https://doi.org/10.1016/S0140-6736(95)90227-9

Szulc P, Chapuy MC, Meunier PJ, Delmas PD. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest 1993; 91: 1769-1774.

https://doi.org/10.1172/JCI116387

Hernandez JL, Garces CM, Sumillera M, Fernandez-Aldasoro EV, Garcia-Ibarbia C, Ortiz-Gomez JA, et al. Aromatase expression in osteoarthritic and osteoporotic bone. Arthritis Rheum 2008; 58: 1696-1700.

https://doi.org/10.1002/art.23500

Apeland T, Mansoor MA, Strandjord RE. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Res 2001; 47: 27-35.

https://doi.org/10.1016/S0920-1211(01)00288-1

McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 2004; 350: 2042-2049.

https://doi.org/10.1056/NEJMoa032739

Casini A, Antel J, Abbate F, Scozzafava A, David S, Waldeck H, et al. Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg Med Chem Lett 2003; 13: 841-845.

https://doi.org/10.1016/S0960-894X(03)00029-5

De Simone G, Di Fiore A, Menchise V, Pedone C, Antel J, Casini A, et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett 2005; 15: 2315-2320.

https://doi.org/10.1016/j.bmcl.2005.03.032

Kim SH, Lee JW, Choi KG, Chung HW, Lee HW. A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy. Epilepsy Behav 2007; 10: 291-295.

https://doi.org/10.1016/j.yebeh.2006.11.007

Cómo citar
1.
Ramírez-Jiménez JJ, Alfaro-Velásquez JM. Efecto de los medicamentos antiepilépticos en el metabolismo de la vitamina D y el impacto negativo relacionado al déficit. Med. Lab. [Internet]. 1 de marzo de 2015 [citado 22 de abril de 2021];21(3-4):131-48. Disponible en: https://medicinaylaboratorio.com/index.php/myl/article/view/116
Publicado
2015-03-01
Sección
Química Clínica
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