Relationship between antiepileptic drugs and biological markers affecting long-term cardiovascular function in children and adolescents

Canadian Journal of Clinical Pharmacology

Volumn 17, Issue 1, 2010, Pages

  Cheng, Laura S ^a,c,d   Prasad, Asuri N ^a,b,d   Rieder, Michael J ^a,b,c,d  

^a UNIVERSITY OF WESTERN ONTARIO   (Canada)

^b CHILDREN S HOSPITAL OF WESTERN ONTARIO   (Canada)

^c ROBARTS RESEARCH INSTITUTE   (Canada)

^d CHILDREN S HEALTH RESEARCH INSTITUTE   (Canada)

Author keywords

Anticonvulsant antiepileptic drugs; Cardiovascular events; Children; Epilepsy; Homocysteine

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ANTICONVULSIVE AGENT; CARBAMAZEPINE; CYTOCHROME P450; ETIRACETAM; FOLIC ACID; HOMOCYSTEINE; LAMOTRIGINE; LIPOPROTEIN; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; VALPROIC ACID;

ABSENCE; ADOLESCENT; AGGRESSION; ANEMIA; ANOREXIA; ANTICONVULSANT THERAPY; ARTICLE; ASTHENIA; ATAXIA; BEHAVIOR DISORDER; BENIGN CHILDHOOD EPILEPSY; BLEEDING DISORDER; BLURRED VISION; BONE DENSITY; BRAIN ATROPHY; BRAIN DISEASE; CARDIOVASCULAR EFFECT; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR RISK; CHEMOTHERAPY INDUCED EMESIS; CHILD; COGNITIVE DEFECT; CONFUSION; DEMENTIA; DEVELOPMENTAL DISORDER; DIPLOPIA; DISTRIBUTION VOLUME; DIZZINESS; DNA POLYMORPHISM; DROWSINESS; DRUG BIOAVAILABILITY; DRUG ELIMINATION; DRUG ERUPTION; DRUG FEVER; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG TRANSFORMATION; DYSARTHRIA; EDEMA; ENDOTHELIAL DYSFUNCTION; ENZYME ACTIVITY; EPILEPSY; EPILEPTIC STATE; FATIGUE; FEBRILE CONVULSION; FLU LIKE SYNDROME; FOCAL EPILEPSY; GAIT DISORDER; GASTROINTESTINAL SYMPTOM; GENERALIZED EPILEPSY; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; GRAND MAL SEIZURE; HAIR LOSS; HUMAN; HYPERAMMONEMIA; HYPERINSULINISM; HYPOCARNITINEMIA; HYPONATREMIA; INFECTION; INSOMNIA; LENNOX GASTAUT SYNDROME; LETHARGY; LIPOPROTEIN BLOOD LEVEL; LIVER FAILURE; MENSTRUAL IRREGULARITY; MENTAL DISEASE; MENTAL INSTABILITY; METABOLIC DISORDER; MONOTHERAPY; MOOD CHANGE; MOOD DISORDER; MOTOR DYSFUNCTION; MYOCLONUS; NAUSEA; NEURAL TUBE DEFECT; NOCTURNAL ENURESIS; NYSTAGMUS; OVARY POLYCYSTIC DISEASE; PANCREATITIS; PSYCHOSIS; RHINITIS; SEDATION; SEIZURE; SIDE EFFECT; SIGNAL TRANSDUCTION; SOMNOLENCE; THROMBOCYTE AGGREGATION; THROMBOCYTOPENIA; TREATMENT DURATION; TREMOR; VASCULAR DISEASE; WEIGHT GAIN;

EID: 77249166056     PISSN: 1198581X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (92)

1. Fisher RS, van Emde Boas W, Blume W, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46(4):470-2.
2. Statistics Canada. National Population Health Survey, 1998-99 (Cycle 3): Household Component. General file. Ottawa: Statistics Canada, Health Statistics Division, 2001.
3. Statistics Canada. Canadian Community Health Survey, Cycle 1.1 (2000-2001). Ottawa: Statistics Canada. Health Statistics Division, 2001.
4. Schwaninger M, Ringleb P, Winter R, et al. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment. Epilepsia 1999;40(3):345-50.
5. Verrotti A, Pascarella R, Trotta D, Giuva T, Morgese G, Chiarelli F. Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine. Epilepsy Res 2000;41(3):253-7.
6. Kurul S, Unalp A, Yis U. Homocysteine levels in epileptic children receiving antiepileptic drugs. J Child Neurol 2007;22(12):1389-92.
7. Vurucu S, Demirkaya E, Kul M, et al. Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy. Prog Neuropsychopharmacol Biol Psychiatry 2008;32(3):844-8.
8. Ono H, Sakamoto A, Eguchi T, et al. Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants. Metabolism 1997;46(8):959-62.
9. Huemer M, Vonblon K, Fodinger M, et al. Total homocysteine, folate, and cobalamin, and their relation to genetic polymorphisms, lifestyle and body mass index in healthy children and adolescents. Pediatr Res 2006;60(6):764-9.
10. Osganian SK, Stampfer MJ, Spiegelman D, et al. Distribution of and factors associated with serum homocysteine levels in children: Child and Adolescent Trial for Cardiovascular Health. JAMA 1999;281(13):1189-96.
11. Schwaninger M, Ringleb P, Annecke A, et al. Elevated plasma concentrations of lipoprotein(a) in medicated epileptic patients. J Neurol 2000;247(9):687-90.
12. Tumer L, Serdaroglu A, Hasanoglu A, Biberoglu G, Aksoy E. Plasma homocysteine and lipoprotein (a) levels as risk factors for atherosclerotic vascular disease in epileptic children taking anticonvulsants. Acta Paediatr 2002;91(9):923-6.
13. Voudris KA, Attilakos A, Katsarou E, et al. Early and persistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy. Epilepsy Res 2006;70(2-3):211-7.
14. Eiris J, Novo-Rodriguez MI, Del Rio M, Meseguer P, Del Rio MC, Castro-Gago M. The effects on lipid and apolipoprotein serum levels of long-term carbamazepine, valproic acid and phenobarbital therapy in children with epilepsy. Epilepsy Res 2000;41(1):1-7.
15. Sozuer DT, Atakil D, Dogu O, Baybas S, Arpaci B. Serum lipids in epileptic children treated with carbamazepine and valproate. Eur J Pediatr 1997;156(7):565-7.
16. Eiris JM, Lojo S, Del Rio MC, et al. Effects of long-term treatment with antiepileptic drugs on serum lipid levels in children with epilepsy. Neurology 1995;45(6):1155-7.
17. Tamura T, Aiso K, Johnston KE, Black L, Faught E. Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy. Epilepsy Res 2000;40(1):7-15.
18. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969;56(1):111-28.
19. Ueland PM, Refsum H, Beresford SA, Vollset SE. The controversy over homocysteine and cardiovascular risk. Am J Clin Nutr 2000;72(2):324-32.
20. Tonstad S, Refsum H, Sivertsen M, Christophersen B, Ose L, Ueland PM. Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives. Pediatr Res 1996;40(1):47-52.
21. Vilaseca MA, Moyano D, Artuch R, et al. Selective screening for hyperhomocysteinemia in pediatric patients. Clin Chem 1998;44(3):662-4.
22. Prengler M, Sturt N, Krywawych S, Surtees R, Liesner R, Kirkham F. Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood. DevMed Child Neurol 2001;43(4):220-5.
23. Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother 2000;34(1):57-65.
24. Ueland PM, Refsum H. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease, and drug therapy. J Lab Clin Med 1989;114(5):473-501.
25. Apeland T, Mansoor MA, Strandjord RE. Antiepileptic drugs as independent predictors of plasma total homocysteine levels. Epilepsy Res 2001;47(1-2):27-35.
26. Morrell MJ. Guidelines for the care of women with epilepsy. Neurology 1998;51(5 Suppl 4):S21-7.
27. Trabetti E. Homocysteine, MTHFR gene polymorphisms, and cardio-cerebrovascular risk. J Appl Genet 2008;49(3):267-82.
28. Huang T, Yuan G, Zhang Z, Zou Z, Li D. Cardiovascular pathogenesis in hyperhomocysteinemia. Asia Pac J Clin Nutr 2008;17(1):8-16.
29. Jacobsen DW. Homocysteine and vitamins in cardiovascular disease. Clin Chem 1998;44(8 Pt 2):1833-43.
30. Hoffer LJ. Homocysteine remethylation and transsulfuration. Metabolism2004;53(11):1480-3.
31. Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999;19:217-46.
32. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270(22):2693-8.
33. Farid FA, Faheem MS, Heshmat NM, Shaheen KY, Saad SS. Study of the homocysteine status in children with chronic renal failure. Am J Nephrol 2004;24(3):289-95.
34. Siniscalchi A, Mancuso F, Gallelli L, Ferreri Ibbadu G, Biagio Mercuri N, De Sarro G. Increase in plasma homocysteine levels induced by drug treatments in neurologic patients. Pharmacol Res 2005;52(5):367-75.
35. Mota C, Fonseca I, Santos MJ, et al. Homocysteine levels in pediatric renal transplant recipients. Transplant Proc 2003;35(3):1093-5.
36. Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med 1998;338(15):1042-50.
37. Diaz-Arrastia R. Homocysteine and neurologic disease. Arch Neurol 2000;57(10):1422-7.
38. Vilaseca MA, Moyano D, Ferrer I, Artuch R. Total homocysteine in pediatric patients. Clin Chem 1997;43(4):690-2.
39. Minniti G, Cerone R, Piana A, Armani U, Lorini R. Plasma and serum total homocysteine concentrations in paediatric patients, evaluated by high-performance liquid chromatography with fluorescence. Clin Chem Lab Med 2000;38(7):675-6.
40. Huemer M, Ausserer B, Graninger G, et al. Hyperhomocysteinemia in children treated with antiepileptic drugs is normalized by folic acid supplementation. Epilepsia 2005;46(10):1677-83.
41. Ubbink JB, van der Merwe A, Delport R, et al. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest 1996;98(1):177-84.
42. Karabiber H, Sonmezgoz E, Ozerol E, Yakinci C, Otlu B, Yologlu S. Effects of valproate and carbamazepine on serum levels of homocysteine, vitamin B12, and folic acid. Brain Dev 2003;25(2):113-5.
43. Yoo JH, Hong SB. A common mutation in the methylenetetrahydrofolate reductase gene is a determinant of hyperhomocysteinemia in epileptic patients receiving anticonvulsants. Metabolism 1999;48(8):1047-51.
44. Lawrence de Koning AB, Werstuck GH, Zhou J, Austin RC. Hyperhomocysteinemia and its role in the development of atherosclerosis. Clin Biochem 2003;36(6):431-41.
45. Dean J, Robertson Z, Reid V, et al. Fetal anticonvulsant syndromes and polymorphisms in MTHFR, MTR, and MTRR. Am J Med Genet A 2007;143A(19):2303-11.
46. Kang SS, Wong PW, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr 1992;12:279-98.
47. Rang HP. Rang and Dale's Pharmacology. 6th ed. Philadelphia, PA: Churchill Livingstone /Elsevier, 2007.
48. Shorvon SD. Handbook of epilepsy treatment: forms, causes and therapy in children and adults. 2nd ed. Malden, Mass.; Oxford: Blackwell Pub., 2005.
49. Pellock JM, Bourgeois BFD, Dodson WE. Pediatric epilepsy: diagnosis and therapy. 3rd ed. New York: Demos Medical Publishing, 2008.
50. Wyllie E, Gupta A, Lachhwani DK. The treatment of epilepsy: principles & practice. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2006.
51. Attilakos A, Papakonstantinou E, Schulpis K, et al. Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy. Epilepsy Res 2006;71(2-3):229-32.
52. Vilaseca MA, Monros E, Artuch R, et al. Antiepileptic drug treatment in children: hyperhomocysteinaemia, B-vitamins and the 677C - >T mutation of the methylenetetrahydrofolate reductase gene. Eur J Paediatr Neurol 2000;4(6):269-77.
53. Unal O, Deda G, Teber S, Ertem M, Akar N. Thrombophilic risk factors in epileptic children treated with valproic Acid. Pediatr Neurol 2009;40(2):102-6.
54. Sener U, Zorlu Y, Karaguzel O, Ozdamar O, Coker I, Topbas M. Effects of common antiepileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6. Seizure 2006;15(2):79-85.
55. Verrotti A, Domizio S, Angelozzi B, Sabatino G, Morgese G, Chiarelli F. Changes in serum lipids and lipoproteins in epileptic children treated with anticonvulsants. J Paediatr Child Health 1997;33(3):242-5.
56. Tan TY, Lu CH, Chuang HY, et al. Long-term antiepileptic drug therapy contributes to the acceleration of atherosclerosis. Epilepsia March 9, 2009. DOI: 10.1111/j.1528-1167.2009.02024.x
57. Stamler JS, Osborne JA, Jaraki O, et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993;91(1):308-18.
58. Wang G, Dai J, Mao J, Zeng X, Yang X, Wang X. Folic acid reverses hyper-responsiveness of LPS-induced chemokine secretion from monocytes in patients with hyperhomocysteinemia. Atherosclerosis 2005;179(2):395-402.
59. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274(13):1049-57.
60. van Beynum IM, Smeitink JA, den Heijer M, te Poele Pothoff MT, Blom HJ. Hyperhomocysteinemia: a risk factor for ischemic stroke in children. Circulation 1999;99(16):2070-2.
61. Annegers JF, Hauser WA, Shirts SB. Heart disease mortality and morbidity in patients with epilepsy. Epilepsia 1984;25(6):699-704.
62. Lodish HF. Molecular cell biology. 5th ed. New York: W.H. Freeman and Company, 2004.
63. Aynaci FM, Orhan F, Orem A, Yildirmis S, Gedik Y. Effect of Antiepileptic drugs on plasma lipoprotein (a) and other lipid levels in childhood. J Child Neurol 2001;16(5):367-9.
64. Van Biervliet JP, Labeur C, Michiels G, Usher DC, Rosseneu M. Lipoprotein(a) profiles and evolution in newborns. Atherosclerosis 1991;86(2-3):173-81.
65. Sonmez FM, Demir E, Orem A, et al. Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes. J Child Neurol 2006;21(1):70-4.
66. Verrotti A, Basciani F, Domizio S, Sabatino G, Morgese G, Chiarelli F. Serum lipids and lipoproteins in patients treated with antiepileptic drugs. Pediatr Neurol 1998;19(5):364-7.
67. Franzoni E, Govoni M, D'Addato S, et al. Total cholesterol, high-density lipoprotein cholesterol, and triglycerides in children receiving antiepileptic drugs. Epilepsia 1992;33(5):932-5.
68. American Academy of Pediatrics. Committee on Nutrition. Cholesterol in childhood. Pediatrics 1998;101(1 Pt 1):141-7.
69. Dean JC, Robertson Z, Reid V, et al. A high frequency of the MTHFR 677C>T polymorphism in Scottish women with epilepsy: possible role in pathogenesis. Seizure 2008;17(3):269-75.
70. Ono H, Sakamoto A, Mizoguchi N, Sakura N. Methylenetetrahydrofolate reductase 677C > T mutation and epilepsy. J Inherit Metab Dis 2000;23(5):525-6.
71. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet 1991;338(8760):131-7.
72. Dean JC, Hailey H, Moore SJ, Lloyd DJ, Turnpenny PD, Little J. Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth. J Med Genet 2002;39(4):251-9.
73. Moore SJ, Turnpenny P, Quinn A, et al. A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet 2000;37(7):489-97.
74. Kaneko S, Battino D, Andermann E, et al. Congenital malformations due to antiepileptic drugs. Epilepsy Res 1999;33(2-3):145-58.
75. Friso S, Choi SW, Girelli D, et al. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status. Proc Natl Acad Sci U S A 2002;99(8):5606-11.
76. Castro R, Rivera I, Ravasco P, et al. 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C - >T and 1298A - >C mutations are associated with DNA hypomethylation. J Med Genet 2004;41(6):454-8.
77. Shelnutt KP, Kauwell GP, Gregory JF, 3rd, et al. Methylenetetrahydrofolate reductase 677C - >T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem 2004;15(9):554-60.
78. Hunt S, Russell A, Smithson WH, et al. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008;71(4):272-6.
79. Kang SS, Zhou J, Wong PW, Kowalisyn J, Strokosch G. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet 1988;43(4):414-21.
80. Kang SS, Wong PW, Susmano A, Sora J, Norusis M, Ruggie N. Thermolabile methylenetetrahydrofolate reductase: an inherited risk factor for coronary artery disease. Am J Hum Genet 1991;48(3):536-45.
81. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10(1):111-3.
82. Alessio AC, Annichino-Bizzacchi JM, Bydlowski SP, Eberlin MN, Vellasco AP, Hoehr NF. Polymorphisms in the methylenetetrahydrofolate reductase and methionine synthase reductase genes and homocysteine levels in Brazilian children. Am J Med Genet A 2004;128A(3):256-60.
83. Ono H, Sakamoto A, Mizoguchi N, Sakura N. The C677T mutation in the methylenetetrahydrofolate reductase gene contributes to hyperhomocysteinemia in patients taking anticonvulsants. Brain Dev 2002;24(4):223-6.
84. Van den Berg M, Boers GH, Franken DG, et al. Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. Eur J Clin Invest 1995;25(3):176-81.
85. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999;340(19):1449-54.
86. Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000;343(22):1608-14.
87. Malm H, Kajantie E, Kivirikko S, Kaariainen H, Peippo M, Somer M. Valproate embryopathy in three sets of siblings: further proof of hereditary susceptibility. Neurology 2002;59(4):630-3.
88. Craig J, Morrison P, Morrow J, Patterson V. Failure of periconceptual folic acid to prevent a neural tube defect in the offspring of a mother taking sodium valproate. Seizure 1999;8(4):253-4.
89. Duncan S, Mercho S, Lopes-Cendes I, et al. Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality. Epilepsia 2001;42(6):750-3.
90. Nebert DW, Russell DW. Clinical importance of the cytochromes P450. Lancet 2002;360(9340):1155-62.
91. Mintzer S, Skidmore CT, Abidin CJ, et al. Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein. Ann Neurol 2009;65(4):448-56.
92. Zighetti ML, Chantarangkul V, Tripodi A, Mannucci PM, Cattaneo M. Determination of total homocysteine in plasma: comparison of the Abbott IMx immunoassay with high performance liquid chromatography. Haematologica 2002;87(1):89-94.