Doses-carga de carbamazepina e difenil-hidantoína: utilização em pacientes de alto risco

Leite, Paulo J. M.; Tsanaclis, Lolita M.; Markourakis, Tânia; Mittencourt, Paulo Rogério M.

doi:10.1590/S0004-282X1987000300008

Resumos

Doses-carga de difenil-hidantoína (lOOOmg) e carbamazepina (600mg) foram administradas oralmente a respectivamente 10 e 6 pacientes com crises epilépticas secundárias a doença aguda neurológica ou síndrome de abstinência alcoólica. No grupo da difenil-hidantoína a idade variou de 12 a 73 anos e as concentrações séricas 2, 4, 6, 8, 12 e 18 horas após a administração foram 7,6, 8,8, 8,7, 8,7, 7,2 e 6,5 mg/ml (média). Não foram anotados efeitos colaterais importantes por um método quantitativo. No grupo da carbamazepina a idade variou de 25 a 56 anos e as concentrações séricas nas mesmas horas foram 3,9, 5,3, 6,5, 7,5, 7,4 e 8,2 mg/ml. Efeitos colaterais foram discretos. Não foi necessária medicação suplementar durante as 24 horas após a administração das doses-carga. Embora ambos os esquemas tenham controlado a situação clínica sem efeitos colaterais relevantes, as concentrações séricas foram sub-terapêuticas no caso da difenil-hidantoína. Sugerimos que a dosecarga ideal de difenil-hidantoína é 1500mg. A dose-carga de carbamazepina foi eficaz e produziu níveis séricos terapêuticos. A estabilidade dos níveis séricos durante o período de estudo torna este esquema útil no controle subagudo de crises epilépticas frequentes, no tratamento de manutenção de estado de mal epiléptico e na síndrome de retirada alcoólica.

Loading-doses of phenytoin (1000mg) and carbamazepine (600mg) were given orally respectively to 10 and 6 patients with uncontrolled epileptic seizures secondary to acute neurological disorders or alcohol withdrawal. In the phenytoin group age varied between 12-73 years and serum concentrations at 2, 4, 6, 8, 12 and 18 hours after drug administration were 7.6, 8.8, 8.7, 8.7, 7.2 and 6.5mg/ml (means). A quantitative method did not detect important side-effects. In the carbamazepine group age varied between 25-56 years and serum concentrations at the same times were 3.9, 5.3, 6.5, 7.5, 7.4 and 8.2 mg/ml. Side-effects were discrete. Further medication was not necessary in the 24 hours after drug administration. Although both regimens controlled the clinical situation without relevant side-effects serum concentrations were sub-therapeutic in the case of phenytoin. We suggest the ideal phenytoin oral loading-dose is 1500mg. The carbamazepine load produced therapeutic concentrations. The stability of serum concentrations for the period of the study shows that these regimens are useful in the subacute control of epileptic seizures in the maintenance treatment of status epilepticus and in alcohol withdrawal.

Doses-carga de carbamazepina e difenil-hidantoína: utilização em pacientes de alto risco

Carbamazepine and phenytoin loading-doses: utilization in high-risk patients

Paulo J. M. Leite^I; Lolita M. Tsanaclis^II; Tânia Markourakis^II; Paulo Rogério M. Mittencourt^I

^IUnidade de Neurologia Clínica, Hospital Nossa Senhora das Graças, Curitiba

^IICentro de Investigações em Neurologia, Faculdade de Medicina, Universidade de São Paulo

RESUMO

Doses-carga de difenil-hidantoína (lOOOmg) e carbamazepina (600mg) foram administradas oralmente a respectivamente 10 e 6 pacientes com crises epilépticas secundárias a doença aguda neurológica ou síndrome de abstinência alcoólica. No grupo da difenil-hidantoína a idade variou de 12 a 73 anos e as concentrações séricas 2, 4, 6, 8, 12 e 18 horas após a administração foram 7,6, 8,8, 8,7, 8,7, 7,2 e 6,5 mg/ml (média). Não foram anotados efeitos colaterais importantes por um método quantitativo. No grupo da carbamazepina a idade variou de 25 a 56 anos e as concentrações séricas nas mesmas horas foram 3,9, 5,3, 6,5, 7,5, 7,4 e 8,2 mg/ml. Efeitos colaterais foram discretos. Não foi necessária medicação suplementar durante as 24 horas após a administração das doses-carga. Embora ambos os esquemas tenham controlado a situação clínica sem efeitos colaterais relevantes, as concentrações séricas foram sub-terapêuticas no caso da difenil-hidantoína. Sugerimos que a dosecarga ideal de difenil-hidantoína é 1500mg. A dose-carga de carbamazepina foi eficaz e produziu níveis séricos terapêuticos. A estabilidade dos níveis séricos durante o período de estudo torna este esquema útil no controle subagudo de crises epilépticas frequentes, no tratamento de manutenção de estado de mal epiléptico e na síndrome de retirada alcoólica.

SUMMARY

Loading-doses of phenytoin (1000mg) and carbamazepine (600mg) were given orally respectively to 10 and 6 patients with uncontrolled epileptic seizures secondary to acute neurological disorders or alcohol withdrawal. In the phenytoin group age varied between 12-73 years and serum concentrations at 2, 4, 6, 8, 12 and 18 hours after drug administration were 7.6, 8.8, 8.7, 8.7, 7.2 and 6.5mg/ml (means). A quantitative method did not detect important side-effects. In the carbamazepine group age varied between 25-56 years and serum concentrations at the same times were 3.9, 5.3, 6.5, 7.5, 7.4 and 8.2 mg/ml. Side-effects were discrete. Further medication was not necessary in the 24 hours after drug administration. Although both regimens controlled the clinical situation without relevant side-effects serum concentrations were sub-therapeutic in the case of phenytoin. We suggest the ideal phenytoin oral loading-dose is 1500mg. The carbamazepine load produced therapeutic concentrations. The stability of serum concentrations for the period of the study shows that these regimens are useful in the subacute control of epileptic seizures in the maintenance treatment of status epilepticus and in alcohol withdrawal.

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Unidade de Neurologia Clinica, Hospital Nossa Senhora das Graças - Rua Alcides Munhoz, J/33 - Mercês - 80510 - Curitiba, PR . Brasil.

1. BITTENCOURT, P.R.M. - Diretrizes gerais. In P.R.M. Bittencourt (ed.): Palestras do II Simpósio Paranaense de Epilepsia, Publicações do Capítulo Paranaense da Liga Brasileira de Epilepsia, 1984, pg. 45.
2. BITTENCOURT, P.R.M. - Epilepsy in Latin America. In J. Laidlaw, A. Richens & J. Oxley: Textbook of Epilepsy. Ed. 3. Churchill-Livingstone, Edinburgh, na prensa.
3. BITTENCOURT, P.R.M. - Particularidades do tratamento farmacológico da epilepsia. In P.C. de Sena (ed.): Novas Achegas sobre Epilepsia. UFBA, Salvador, 1980.
4. BITTENCOURT, P.R.M. - The effect of some centrally acting drugs on saccadic and smooth pursuit eye movements in man. PhD Thesis, University of London. London, 1981.
5. BITTENCOURT, P.R.M.; GRESTRY, M.A. & RICHENS, A. - Quantitative assessment of smooth-pursuit eye movements in healthy and epileptic subjects. J. Neurol. Neurosurg. Psychiat. 43:119, 1980.
6. BITTENCOURT, P.R.M.; PERÜCCA, E. & CREMA, A. - Cerebellar toxicity of anti epileptic drugs. In K. Blum & L. Manzo (eds.): Neurotoxicology. Marcel Dekker, New York, 1985, pg. 233.
7. BITTENCOURT, P.R.M. & RICHENS, A. - Assessment of antiepileptic drug toxicity by eye movements. In P.A. Buser, W.A. Cobb & T. Okuna (eds.): Kyoto Symposia. (EEG Supplement 36), Elsevier Biomedical, Amsterdam, 1982, pg. 467.
8. BITTENCOURT, P.R.M. & RICHENS, A. - Concentrações séricas após doses únicas de drogas antiepilépticas: conceito de dose-carga. Arq. Neuro-Psiquiat. (São Paulo) 42:11, 1985.
9. BITTENCOURT, P.R.M.; SMITH, A.T.; LLOYD, D.S.L. & RICHENS, A. - Determination of smooth pursuit eye movement velocity in humans by computer. Electroenceph. clin. Neurophysiol. 54:399, 1982.
10. BITTENCOURT, P.R.M.; WADE, P.; SMITH, AT. & RICHENS, A. - Benzodiazepines impair smooth pursuit eye movements. Brit. J. clin. Pharmacol. 15:259, 1983.
11. BITTENCOURT, P.R.M.; WADE, P.; SMITH, A.T. & RICHENS, A. - The relationship between peak velocity of saccadic eye movement and serum benzodiazepine concentration. Brit. J. clin. Pharmacol. 12:532, 1981.
12. BJORKQUIST, S.E.; ISOHANNIM, M.; MAKELA R. & MALINEN, L. - Ambulant treatment of alcohol withdrawal symptoms with carbamazepine: a formal multicentre double-blind comparison with placebo. Acta, psychiat. scand. 53:333, 1976.
13. BOOKER, H.E. & DARCEY, B. - Serum concentration of free diphenylhidantoin and their relationship to clinical intoxication. Epilepsia 14:177, 1973.
14. DAM, M. - Phenitoin toxicity. In D.M. Woodbury, J.K. Penry & C.E. Pippenger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 247.
15. GRIFFITHS, A.N.; MARSHALL, R.W. & RICHENS, A. - Saccadic eye movement analysis as a measure of drug effects on human psychomotor performance. Brit. J. clin. Pharmacol. 18:735, 1984.
16. HÖPPENER, R.J.; KUYER, A.; MIJER, J.W.A. & MULSMAN, J. - Correlation between daily flutuations of carbamazepine serum levels and intermitent side-effects. Epilepsia 21:341, 1980.
17. MASCAN, R.L.- Carbamazepine: Neurotoxicity. In D.M. Woodbury, J.K. Penry & C.E. Pippenger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 521.
18. MARSDEN, C.E. & REYNOLDS, E.H. - Neurology. In J. Laidlaw & A. Richens (eds.): Textbook of Epilepsy. Churchill-Livingstone, Edinburgh, 1982, pg. 116.
19. REYNOLDS, E.H. - Serum levels of anticonvulsant drugs: interpretation and clinical value. Pharmacol. Ther. 8:217, 1979.
20. REYNOLDS, E.M.; SHORVON, S.D.; GALBRAITH, A.W.; CHADWICK, D.; C.I. DELLAPORTAS & VY DELINGUN - Phenytoin monotherapy for epilepsy: a long-term prospective study, assisted by serum level monitoring in previously untreated patients. Epilepsia 22:475, 1981.
21. RIKER, W.K.; DOWNES, H.; OLSEN, G.D. & SMITH, B. - Conjugate lateral gaze nystagmus and free Phenytoin concentration in plasma: lack of correlation. Epilepsia 19:93, 1978.
22. SILVADO, C.E.S. & BITTENCOURT, P.R.M. - Classificação das crises epilépticas. In P.R.M. Bittencourt (ed.): Palestras do II Simpósio Paranaense de Epilepsia. Publicações do Capítulo Paranaense da Liga Brasileira de Epilepsia, 1984, pg. 16.
23. STRANDJORD, R.E. & JOHANNESSEN, S.I. - Single-drug therapy with carbamazepine in patients with epilepsy: serum levels and clinical effect. Epilepsia 21:655, 1980.

Datas de Publicação

Publicação nesta coleção
22 Jun 2011
Data do Fascículo
Set 1987

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BITTENCOURT, P.R.M. - Diretrizes gerais. In P.R.M. Bittencourt (ed.): Palestras do II Simpósio Paranaense de Epilepsia, Publicações do Capítulo Paranaense da Liga Brasileira de Epilepsia, 1984, pg. 45.

[2] 2. BITTENCOURT, P.R.M. - Epilepsy in Latin America. In J. Laidlaw, A. Richens & J. Oxley: Textbook of Epilepsy. Ed. 3. Churchill-Livingstone, Edinburgh, na prensa.

[3] 3. BITTENCOURT, P.R.M. - Particularidades do tratamento farmacológico da epilepsia. In P.C. de Sena (ed.): Novas Achegas sobre Epilepsia. UFBA, Salvador, 1980.

[4] 4. BITTENCOURT, P.R.M. - The effect of some centrally acting drugs on saccadic and smooth pursuit eye movements in man. PhD Thesis, University of London. London, 1981.

[5] 5. BITTENCOURT, P.R.M.; GRESTRY, M.A. & RICHENS, A. - Quantitative assessment of smooth-pursuit eye movements in healthy and epileptic subjects. J. Neurol. Neurosurg. Psychiat. 43:119, 1980.

[6] 6. BITTENCOURT, P.R.M.; PERÜCCA, E. & CREMA, A. - Cerebellar toxicity of anti epileptic drugs. In K. Blum & L. Manzo (eds.): Neurotoxicology. Marcel Dekker, New York, 1985, pg. 233.

[7] 7. BITTENCOURT, P.R.M. & RICHENS, A. - Assessment of antiepileptic drug toxicity by eye movements. In P.A. Buser, W.A. Cobb & T. Okuna (eds.): Kyoto Symposia. (EEG Supplement 36), Elsevier Biomedical, Amsterdam, 1982, pg. 467.

[8] 8. BITTENCOURT, P.R.M. & RICHENS, A. - Concentrações séricas após doses únicas de drogas antiepilépticas: conceito de dose-carga. Arq. Neuro-Psiquiat. (São Paulo) 42:11, 1985.

[9] 9. BITTENCOURT, P.R.M.; SMITH, A.T.; LLOYD, D.S.L. & RICHENS, A. - Determination of smooth pursuit eye movement velocity in humans by computer. Electroenceph. clin. Neurophysiol. 54:399, 1982.

[10] 10. BITTENCOURT, P.R.M.; WADE, P.; SMITH, AT. & RICHENS, A. - Benzodiazepines impair smooth pursuit eye movements. Brit. J. clin. Pharmacol. 15:259, 1983.

[11] 11. BITTENCOURT, P.R.M.; WADE, P.; SMITH, A.T. & RICHENS, A. - The relationship between peak velocity of saccadic eye movement and serum benzodiazepine concentration. Brit. J. clin. Pharmacol. 12:532, 1981.

[12] 12. BJORKQUIST, S.E.; ISOHANNIM, M.; MAKELA R. & MALINEN, L. - Ambulant treatment of alcohol withdrawal symptoms with carbamazepine: a formal multicentre double-blind comparison with placebo. Acta, psychiat. scand. 53:333, 1976.

[13] 13. BOOKER, H.E. & DARCEY, B. - Serum concentration of free diphenylhidantoin and their relationship to clinical intoxication. Epilepsia 14:177, 1973.

[14] 14. DAM, M. - Phenitoin toxicity. In D.M. Woodbury, J.K. Penry & C.E. Pippenger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 247.

[15] 15. GRIFFITHS, A.N.; MARSHALL, R.W. & RICHENS, A. - Saccadic eye movement analysis as a measure of drug effects on human psychomotor performance. Brit. J. clin. Pharmacol. 18:735, 1984.

[16] 16. HÖPPENER, R.J.; KUYER, A.; MIJER, J.W.A. & MULSMAN, J. - Correlation between daily flutuations of carbamazepine serum levels and intermitent side-effects. Epilepsia 21:341, 1980.

[17] 17. MASCAN, R.L.- Carbamazepine: Neurotoxicity. In D.M. Woodbury, J.K. Penry & C.E. Pippenger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 521.

[18] 18. MARSDEN, C.E. & REYNOLDS, E.H. - Neurology. In J. Laidlaw & A. Richens (eds.): Textbook of Epilepsy. Churchill-Livingstone, Edinburgh, 1982, pg. 116.

[19] 19. REYNOLDS, E.H. - Serum levels of anticonvulsant drugs: interpretation and clinical value. Pharmacol. Ther. 8:217, 1979.

[20] 20. REYNOLDS, E.M.; SHORVON, S.D.; GALBRAITH, A.W.; CHADWICK, D.; C.I. DELLAPORTAS & VY DELINGUN - Phenytoin monotherapy for epilepsy: a long-term prospective study, assisted by serum level monitoring in previously untreated patients. Epilepsia 22:475, 1981.

[21] 21. RIKER, W.K.; DOWNES, H.; OLSEN, G.D. & SMITH, B. - Conjugate lateral gaze nystagmus and free Phenytoin concentration in plasma: lack of correlation. Epilepsia 19:93, 1978.

[22] 22. SILVADO, C.E.S. & BITTENCOURT, P.R.M. - Classificação das crises epilépticas. In P.R.M. Bittencourt (ed.): Palestras do II Simpósio Paranaense de Epilepsia. Publicações do Capítulo Paranaense da Liga Brasileira de Epilepsia, 1984, pg. 16.

[23] 23. STRANDJORD, R.E. & JOHANNESSEN, S.I. - Single-drug therapy with carbamazepine in patients with epilepsy: serum levels and clinical effect. Epilepsia 21:655, 1980.