TOXICIDAD HEPÁTICA Y HEMATOLÓGICA DE LA CARBAMAZEPINA EN LA EPILEPSIA FARMACORRESISTENTE Y SU RELACIÓN CON VARIABLES CLÍNICAS / HEPATIC AND HEMATOLOGICAL TOXICITY OF CARBAMAZEPINE IN DRUG-RESISTANT EPILEPSY AND ITS RELATIONSHIP WITH CLINICAL VARIABLES
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Introducción: La epilepsia es un trastorno neurológico complejo que se caracteriza por la presencia de crisis espontáneas recurrentes. Aproximadamente el 30% de los pacientes con epilepsia no responden el tratamiento farmacológico constituyendo el grupo de pacientes con epilepsia farmacorresistente (EFR).
Objetivo: analizar la toxicidad de la carbamazepina (CBZ) en pacientes con EFR mediante la evaluación de las concentraciones séricas de este fármaco, así como medir variables de química sanguínea y hematológicas y su relación con parámetros clínicos como: número de fármacos antiepilépticos, tiempo de evolución y número de crisis.
Materiales y métodos: Se estudiaron 19 pacientes con EFR. Se midió por cromatografía liquida de alta resolución la concentración de CBZ y por método enzimático y colorimétrico las variables hematológicas y de química sanguínea respectivamente.
Resultados: El 42,11% de los pacientes mostraron toxicidad ligera a la CBZ. Existe correlación positiva entre la CBZ y la gamma glutamil transferasa (GGT). Se evidenció una correlación entre el tiempo de evolución y el conteo de leucocitos (p≤0.03) en el sexo femenino. En el sexo masculino, se correlacionó positivamente el número de farmacos con el ácido úrico (p≤0.0009), el conteo de hematíes (p≤0.04), la hemoglobina (p≤0.02) y el hematocrito (p≤0.02).
Conclusiones: Estos datos sustentan la presencia de toxicidad ligera por CBZ relacionada con daño hepático en un porcentaje de pacientes con EFR lo que hace importante y necesario el monitoreo farmacológico. Se aportan nuevas evidencias de la relación entre variables clínicas, parámetros de químicas sanguíneas y hematológicas en estos pacientes.
Abstract
Objective: to analyze the toxicity of carbamazepine (CBZ) in patients with EFR by evaluating the serum concentrations of this drug, as well as to measure blood chemistry and hematological variables and their relationship with clinical parameters such as: number of antiepileptic drugs, time of evolution and number of crises.
Methodical: 19 patients with EFR were studied. The concentration of CBZ was measured by high-performance liquid chromatography and by enzymatic and colorimetric method the hematological and blood chemistry variables, respectively.
Results: 42.11% of the patients showed slight toxicity to CBZ. There is a positive correlation between CBZ and gamma glutamyl transferase (GGT). There was a correlation between the evolution time and the leukocyte count (p≤0.03) in the female sex. In males, the number of drugs was positively correlated with uric acid (p≤0.0009), red cell count (p≤0.04), hemoglobin (p≤0.02) and hematocrit (p≤0.02).
Conclusions: These data support the presence of mild toxicity due to CBZ related to liver damage in a percentage of patients with EFR, which makes pharmacological monitoring important and necessary. New evidence is provided of the relationship between clinical variables, blood chemistry and hematological parameters in these patients.
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Referencias
Engel J. What can we do for people with drug-resistant epilepsy?: The 2016 Wartenberg Lecture. Neurology. 2016;87(23):2483-9.
Tang F, Hartz AMS, Bauer B. Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers. Frontiers in neurology. 2017;8:301.
Morales Chacón L, Garcia Maeso I, Baez Martin M, Bender del Busto J, García Navarro M, Quintanal Cordero N, et al. Long-Term Electroclinical and Employment Follow up in Temporal Lobe Epilepsy Surgery. A Cuban Comprehensive Epilepsy Surgery Program. Behavioral Sciences. 2018;8(2):19.
Greenwood RS. Adverse effects of antiepileptic drugs. Epilepsia. 2000;41 Suppl 2:S42-52.
Aldenkamp AP, Weber B, Overweg-Plandsoen WC, Reijs R, van Mil S. Educational underachievement in children with epilepsy: a model to predict the effects of epilepsy on educational achievement. Journal of child neurology. 2005;20(3):175-80.
Mintzer S. Metabolic consequences of antiepileptic drugs. Current opinion in neurology. 2010;23(2):164-9.
Hadzagic-Catibusic F, Hasanbegovic E, Melunovic M, Zubcevic S, Uzicanin S. Effects of Carbamazepine and Valproate on Serum Aspartate Aminotransferase, Alanine Aminotransferase and Gamma - Glutamyltransferase in Children. Medical archives (Sarajevo, Bosnia and Herzegovina). 2017;71(4):239-42.
García MP, Serrano J, Fernandez-Villalba E, Briz E, Gómez I. Review of carbamazepine-induced toxicity cases at a general hospital over a period of 5 years. Farmacia Hospitalaria. 2002;25:332-7.
Talaat FM, Kamel T, Rabah AM, Ahmed SM, El-Jaafary SI, Abdelaziz GH. Epilepsy and antiepileptic drugs: risk factors for atherosclerosis. IntJNeurosci. 2015;125(7):507-11.
Leis K, Mazur E, Szyperski P, Aleksiewicz T, Jamrożek T, Lipa K, et al. Carbamazepine-hematologic effects of the use. Journal of Education, Health and Sport. 2018;8(8):51-60.
Çağ İ, Altun Y, Altunışık E. Do antiepileptic drugs have any effect on Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratio? Medical Science and Discovery. 2019;6(4):76-81.
Aliyu H, Ayo J, Ambali S, Kawu M, Aluwong T. Heamatobiochemical Alterations Induced by Carbamazepine and Phenytoin: Mini Review. Biochem Pharmacol (Los Angel). 2016;5(219):2167-0501.1000219.
SNI SO, Mazlam N, Kallarakkal T. Evaluation of Carbamazepine Pharmacotherapy In Patients With Trigeminal Neuralgia. Annals of Dentistry University of Malaya. 2016;23(2):20-7.
Brahmi N, Kouraichi N, Abderrazek H, Thabet H, Amamou M. Clinical experience with carbamazepine overdose: relationship between serum concentration and neurological severity. Journal of clinical psychopharmacology. 2008;28(2):241-3.
Acikgoz M, Paksu MS, Guzel A, Alacam A, Alacam F. Severe Carbamazepine Intoxication in Children: Analysis of a 40-Case Series. Medical science monitor : international medical journal of experimental and clinical research. 2016;22:4729-35.
Wang G-X, Wang D-W, Liu Y, Ma Y-H. Intractable epilepsy and the P-glycoprotein hypothesis. International Journal of Neuroscience. 2016;126(5):385-92.
French JA, Gidal BE. Antiepileptic drug interactions. Epilepsia. 2000;41:S30-S6.
Lopez González R. Epilepsia, tratamiento farmacológico y su monitoreo. Revista Cúpula. 2016;30(2):44-53.
Umarje S, Diwan A, Raut A. Suspected hepatotoxicity and thrombocytopenia: Sodium valproate and carbamazepine. CHRISMED Journal of Health and Research. 2018;5(1):57.
Ren T, Xiao M, Yang M, Zhao J, Zhang Y, Hu M, et al. Reduced Systemic and Brain Exposure with Inhibited Liver Metabolism of Carbamazepine After Its Long-Term Combination Treatment with Piperine for Epilepsy Control in Rats. The AAPS journal. 2019;21(5):90.
Pereira LR, Velasco TR, Ceiki-Sakamoto A, de Carvalho D. [Evaluation of the drug interaction between carbamazepine and lamotrigine in the treatment of refractory epilepsy patients]. Revista de neurologia. 2006;43(2):74-7.
Sanchez-Romero A, Mayordomo-Aranda A, Garcia-Delgado R, Duran-Quintana JA. Probable interaction between trazodone and carbamazepine. Pharmacopsychiatry. 2011;44(4):158-9.
Bender del Busto JE, Hernandez Toledo L. Considerations in the treatment of the patient with epilepsy. A review article. Revista Habanera de Ciencias Médicas. 2017;16(6):1059-72.
Ahmed SN, Siddiqi ZA. Antiepileptic drugs and liver disease. Seizure - European Journal of Epilepsy. 2006;15(3):156-64.
Benedetti MS, Whomsley R, Baltes E, Tonner F. Alteration of thyroid hormone homeostasis by antiepileptic drugs in humans: involvement of glucuronosyltransferase induction. European journal of clinical pharmacology. 2005;61(12):863-72.
Čepelak I, Grubišić TŽ, Mandušić A, Rekić B, Leniček J. Valproate and carbamazepine comedication changes hepatic enzyme activities in sera of epileptic children. Clinica chimica acta. 1998;276(2):121-7.
Svalheim S, Luef G, Rauchenzauner M, Mørkrid L, Gjerstad L, Taubøll E. Cardiovascular risk factors in epilepsy patients taking levetiracetam, carbamazepine or lamotrigine. Acta neurologica Scandinavica. 2010;122:30-3.
Consoli D, Bosco D, Postorino P, Galati F, Plastino M, Perticoni G, et al. Levetiracetam versus carbamazepine in patients with late poststroke seizures: a multicenter prospective randomized open-label study (EpIC Project). Cerebrovascular diseases. 2012;34(4):282-9.
Lorigados Pedre L, Gallardo J, Morales Chacón L, Vega García A, Flores-Mendoza M, Neri-Gómez T, et al. Oxidative stress in patients with drug resistant partial complex seizure. Behavioral Sciences. 2018;8(6):59.
Pedre LL, Hung MLD, Gallardo J, Chacón LMM, Díaz BOE, Fraguela MEG, et al. Neuroinflamación y estrés oxidativo en pacientes con crisis focales complejas farmacorresistentes. Revista Cubana de Neurología y Neurocirugía. 2016;6(1):14-5.
Abate MV, Stocco G, Devescovi R, Carrozzi M, Pierobon C, Valencic E, et al. Carbamazepine-induced thrombocytopenic purpura in a child: Insights from a genomic analysis. 2016;59.
Hómez AC, Jiménez M, Luna JR, Salazar JG, Peña JA. Trastornos hematológicos en pacientes tratados con carbamazepina, que acuden al Instituto Hospital Autónomo Universitario de Los Andes Mérida-Venezuela. Rev Fac Farm(Merida). 2004:22-6.
Ndrepepa G, Braun S, Schunkert H, Laugwitz K-L, Kastrati A. Gamma-glutamyl transferase and prognosis in patients with coronary artery disease. Clinica Chimica Acta. 2016;452:155-60.
Hussein R, Nie X, Northwood D. An investigation of ceramic coating growth mechanisms in plasma electrolytic oxidation (PEO) processing. Electrochimica Acta. 2013;112:111-9.
Brodie MJ, Zuberi SM, Scheffer IE, Fisher RS. The 2017 ILAE classification of seizure types and the epilepsies: what do people with epilepsy and their caregivers need to know? Epileptic disorders : international epilepsy journal with videotape. 2018;20(2):77-87.
Lorigados Pedre L, Morales Chacón L, Pavón Fuentes N, Robinson Agramonte M, Serrano Sánchez T, Cruz-Xenes R, et al. Follow-up of peripheral IL-1β and IL-6 and relation with apoptotic death in drug-resistant temporal lobe epilepsy patients submitted to surgery. Behavioral Sciences. 2018;8(2):21.
Wang FS, Goh DLM, Ong HT. Urea cycle disorder presenting as bilateral mesial temporal sclerosis - an unusual cause of seizures: a case report and review of the literature. Journal of medical case reports. 2018;12(1):208.
Joshi R, Tripathi M, Gupta P, Gulati S, Gupta YK. Adverse effects & drug load of antiepileptic drugs in patients with epilepsy: Monotherapy versus polytherapy. The Indian journal of medical research. 2017;145(3):317-26.
Kwan P, Brodie MJ. Refractory epilepsy: mechanisms and solutions. Expert review of neurotherapeutics. 2006;6(3):397-406.
Mallet L, Spinewine A, Huang A. The challenge of managing drug interactions in elderly people. The Lancet. 2007;370(9582):185-91.
Berg AT, Zelko FA, Levy SR, Testa FM. Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes: a prospective cohort study. Neurology. 2012;79(13):1384-91.
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