Dose-Related Adverse Effects of Anticonvulsants

Drug Safety - Tập 14 - Trang 299-328 - 2012
Allan S. Troupin1
1Louisiana State University School of Medicine, New Orleans, USA

Tóm tắt

The serum concentration at which a given drug has full efficacy in delivering seizure control bears no predictable relationship to the concentration at which adverse effects will appear. In theory, the threshold for adverse effects should be considerably higher than that for efficacy. For each agent this obviously happens most of the time, or the anticonvulsant would not be on the market, but there are also patients in whom this relationship is reversed. The adverse effects of this class of drugs are discussed from three points of view: the adverse effect type, the kinetic factors that so frequently determine the presence of adverse effects, and the specific characteristics of each drug. Some less well recognised adverse effects syndromes that are not strictly dose related are considered. The importance of adverse effects in therapeutic monitoring is then addressed, and some strategies for maximising efficacy without the burden of long term functional impairment or distress are discussed. The usefulness of monotherapy is stressed with due attention to rational choice of second drugs, when necessary, based on mechanisms of antiepileptic action and adverse effects profiles. While most of these symptoms evolve gradually, there are times when acute, drastic, and even life threatening clinical overdose situations present themselves. Special attention is given to these scenarios, drawing on the drug profiles and clinical pharmacokinetics that define these events to propose methods of coping with the problems efficiently and effectively.

Tài liệu tham khảo

Riker WK, Downes H, Olsen GD, et al. Conjugate lateral gaze nystagmus and free phenytoin concentrations in plasma: lack of correlation. Epilepsia 1978; 19: 93–8 Troupin AS, Ojemann LM, Halpern LM, et al. Tegretol® (carbamazepine) — a double-blind comparison with Dilantin® (phenytoin). Neurology 1977; 27: 511–9 Devinsky O. Clinical uses of the quality-of-life in epilepsy inventory. Epilepsia 1993; 34Suppl. 4: s39–S44 Schain RJ, Ward JW, Guthrie D. Carbamazepine as an anticonvulsant in children. Neurology 1977; 27: 476–80 Rodin EA, Rim CS, Kitano H, et al. A comparison of the effectiveness of primidone versus carbamazepine in epileptic outpatients. J Nerv Ment Dis 1976; 163: 41–6 Dodrill CB. Diphenylhydantoin serum levels, toxicity, and neuropsychological performance in patients with epilepsy. Epilepsia 1975; 16: 593–600 Yanai J, Bergman I. Neuronal deficits after neonatal exposure to phenobarbital. Exp Neurol 1981; 73: 199–208 Meador KJ, Loring DW, Moore EE, et al. Comparative cognitive effects of phenobarbital, phenytoin, and valproate in healthy adults. Neurology 1995; 45: 1494–9 Troupin AS, Green JR, Levy RH. Carbamazepine as an anticonvulsant — a pilot study. Neurology 1974; 24: 863–9 Johannessen SI, Henriksen O. Comparison of the serum concentration profiles of tegretol and two new slow release preparations. In: Wolf P, Dam M, Janz D, et al., editors. Advances in epileptology. New York: Raven Press; 16: 421–4 Klotz U. Bioavailability of a slow release preparation of valproic acid under steady-state conditions. Int J Clin Pharmacol Ther Toxicol 1982; 20(1): 24–6 Rambeck B. Pharmacologic interactions of methsuximide with phenobarbital and phenytoin in hospitalized epileptic patients. Epilepsia 1979; 20: 147–56 Richens A, Ahmad S. Controlled trial of sodium valproate in severe epilepsy. BMJ 1975; 4: 255–6 Leppik IE. Felbamate. Epilepsia 1995; 36Suppl. 2: s66–S72 Troupin AS, Friel PN, Wilensky AJ, et al. Evaluation of clorazepate (Tranxene®) as an anticonvulsant — a pilot study Neurology 1979; 29: 458–66 Mattson RH, Cramer JA, Williamson PD, et al. Valproic acid in epilepsy: clinical and pharmacological effects. Ann Neurol 1978; 3: 20–5 Bowdle TA, Patel IH, Levy RH, et al. Valproic acid. Dosage and plasma protein binding and clearance. Clin Pharmacol Ther 1980; 28: 486–92 Fraser GD, Ludden TM, Evens RP, et al. Displacement of phenytoin from plasma binding sites by salicylate. Clin Pharmacol Ther 1980; 27: 165–9 Boggs J, Delorenzo RJ. The use of antiepileptic medications in renal and liver disease. In: Wyllie E. The treatment of epilepsy: principles and practices. Philadelphia: Lea & Febiger, 1993: 835–43 Troupin AS, Johannessen SI. Epilepsy in the elderly: a pharmacologic perspective. In: Smith DB, editor. Epilepsy: current approach to diagnosis and therapy. New York: Raven Press, 1990: 141–53 Whyte MP, Dekaban AS. Metabolic fate of phenobarbital. A quanitative study of p-hydroxyphenobarbital elimination in man. Drug Metab Disp 1977; 5: 63–70 Leppik IE. Antiepileptic drugs in development: prospects for the near future. Epilepsia 1994; 35 (suppl. 4): S29–S40 Hussein G, Troupin AS, Montouris GD. Gabapentin interaction with felbamate. Neurology. In press Glaser GH. Diphenlyhydantoin: toxicity. In: Woodbury DM, Penry JK, Schmidt RP, editors. Antiepileptic Drugs. New York: Raven Press, 1972: 219–26 Dodrill CB, Troupin AS. Neuropsychological effects of carbamazepine and phenytoin: a reanalysis. Neurology 1991; 41: 141–4 Troupin AS, Ojemann LM, Dodrill CB. Mephenytoin (Mesantoin®) — a reappraisal. Epilepsia 1976; 17: 403–14 Troupin AS, Ojemann LM. Paradoxical intoxication — a complication of anticonvulsant administration. Epilepsia 1975; 16: 753–8 Kalff R, Houtkooper MA, Meyer JW, et al. Carbamazepine and serum sodium levels. Epilepsia 1984; 25: 390–7 Kerr BM, Levy RH. Carbamazepine epoxide. In: Levy R, Mattson R, Penry JK, et al., editors. Antiepileptic drugs. New York: Raven Press, 1989: 505–20 Murphy JV, Marquard K. Asymptomatic hyperammonemia in patients receiving valproic acid. Arch Neurol 1982; 39: 591–2 Tartara A, Manni R. Sodium valproate ‘encephalopathy’: report of three cases with generalised epilepsy. Ital J Neurol Sci. 1985; 6: 93–5 Karas BJ, Wilder BJ, Hammond EJ, et al. Treatment of valproate tremors. Neurology 1983; 39: 1380–2 Jeavons PM, Clark JE, Harding GFA. Valproate and curly hair [letter]. Lancet 1977; 1977; 359 Farwell JR, Lee YJ, Hirtz DG, et al. Phenobarbital for febrile seizures — effects on intelligence and on seizure recurrence. N Engl J Med 1990; 322: 364–9 Reynolds EH, Travers RD. Serum anticonvulsant concentrations in epileptic patients with mental symptoms. A preliminary report. Br J Psychiatry 1974; 124: 440–5 Rivinus TM. Psychiatric effects of the anticonvulsant regimens. J Clin Psychopharmacol 1982; 2: 165–92 Sher A, Andersen JM, Bhatia SC. Primidone-induced catatonic schizophrenia. Drug Intell Clin Pharm 1983; 17: 551–2 Dreifuss FE. Ethosuximide toxicity. In: Levy RH, Mattson R, Meldrum BM, editors. Antiepileptic Drugs. 3rd ed. New York: Raven Press, 1989: 699–705 Brown TR. Methsuximide. In: Levy RH, Mattson R, Meldrum BM, editors. Antiepileptic Drugs. 3rd ed. New York: Raven Press, 1989: 707–14 Lander CM, Eadie MJ, Tyrer J. Interactions between anticonvulsants. Proc Aust Assoc Neuro 1975; 12: 111–16 Richens A. Clinical pharmacokinetics of Gabapentin. In: Chadwick D, editor. New trends in epilepsy management: the role of Gabapentin. London: Royal Society of Medicine Services 1993: 41–6 McLean MJ. Gabapentin. Epilepsia 1995; 36Suppl. 2: s73–S86 Messenheimer JM. Lamotrigine. Epilepsia 1995; 36Suppl. 2: s97–S94 Troupin AS, Maguire D, Haddad H, et al. Phenacemide: a new clinical pharmacologic perspective. J Epilepsy 1991; 4: 189–98 Houghton GW, Richens A. The effect of benzodiazepines and pheneturide on phenytoin metabolism in man. Br J Clin Pharmacol 1974; 1: 344–5 Troupin AS. Antiepileptic drug therapy: a clinical overview. In: Wyllie E, editor. Treatment of epilepsy: principles and practice. Philadelphia: Lea & Febiger, 1993: 785–90 Kaneko S, Otani K, Fukushima Y, et al. Teratogenicity of antiepileptic drugs: analysis of possible risk factors. Epilepsia 1988; 29: 459–67 Dodrill CB. Effects of antiepileptic drugs on behaviour. In: Devinsky O, Theodore WH, editors. Epilepsy and behaviour. New York: Wiley-Liss, 1991: 37–46 Jeavons PM, Clark JE. Sodium valproate in treatment of epilepsy. BMJ 1974; 2: 584–6 Comstock EG, Falkner TP, Boisaubin EV. Studies on the efficacy of gastric lavage as practiced in the large metropolitan hospital. Clin Toxicol 1981; 18: 581–97 Cooney DO. Activated charcoal: antidotal and other medicinal uses. New York, Marcel Dekker, 1980 Rumack BH, Rosen P. Emesis: safe and effective? [editorial]. Ann Emerg Med 1981; 10: 551 Spivey WH. Flumenazil and seizures: analysis of 43 cases. Clin Ther 1992; 14(2): 292–305