Hostname: page-component-745bb68f8f-cphqk Total loading time: 0 Render date: 2025-01-23T15:26:03.206Z Has data issue: false hasContentIssue false
  • English
  • Français

Acute and Chronic Toxicity of Antiepileptic Medications: a Selective Review

Published online by Cambridge University Press:  18 September 2015

Peter Camfield  and
Carol Camfield
Peter Camfield
Affiliation:
Izaak Walton Killam Hospital for Children, Dalhousie University Medical School, Halifax
Carol Camfield*
Affiliation:
Izaak Walton Killam Hospital for Children, Dalhousie University Medical School, Halifax
*
Izaak Walton Killam Children’s Hospital, 5850 University Avenue, P.O. Box 3070, Halifax, Nova Scotia B3J 3G9
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Acute and chronic toxicity complicates all antiepileptic medications (AED) and is idiosyncratic. Acute toxicity can be categorized into 1) acute brain dysfunction or 2) acute organ dysfunction when AED’s are started. Despite promising in vitro lymphocyte testing, anticipation of acute reactions cannot be offered. Furthermore, screening for AED toxicity by routine blood and urine tests in asymptomatic patients is of doubtful value and should be abandoned. Patients should be informed of possible reactions and immediately report early symptoms. Treatment for acute reactions is largely unstudied. It is unclear how to reintroduce AED’s following acute reactions. Often patients are sensitive to drugs with a similar chemical structure. The “desensitization” protocol of Purvis may be of merit. Three major chronic toxicities of AED’s have been noted – soft tissue and gum hypertrophy, progressive ataxia, and peripheral neuropathy. New AED’s require careful post-marketing surveillance since long term toxicity data are not yet available.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 21 , Issue S3 , August 1994 , pp. S7 - S11
Copyright
Copyright © Canadian Neurological Sciences Federation 1994

References

REFERENCES

1.Willmore, JL., Wheless, JW.Adverse effects of antiepileptic drugs. In: Wyllie, E., ed. The Treatment of Epilepsy: Principles and Practice. Philadelphia: Lea & Febiger, 1993: 824–834.Google Scholar
2.Schmidt, D., Jacob, R.Clinical and laboratory monitoring of antiepileptic medication. Ibid: 798–809.Google Scholar
3.Reynolds, EH.Chronic antiepileptic toxicity: a review. Epilepsia 1975; 16:319–352.CrossRefGoogle ScholarPubMed
4.Schmidt, D.>Adverse Effects of Antiepileptic Drugs. Raven Press New York, 1982.Google Scholar
5.Camfield, PR., Camfield, CS., Smith, E., Tibbies, JR.Newly treated childhood epilepsy: a prospective study of recurrences and side effects. Neurology 1985; 35: 722–725.CrossRefGoogle ScholarPubMed
6.Mattson, RH., Cramer, JA., Collins, JF., et al. Comparison of carbamazepine, phenobarbital, phenytoin and primidone in partial and secondarily generalized tonic-clonic seizures. N Eng J Med 1985; 313: 145–151.CrossRefGoogle ScholarPubMed
7.Pelekanos, J., Camfield, PR., Camfield, CS., Gordon, K.Allergic rash due to antiepileptic drugs: clinical features and management. Epilepsia 1991; 32(4): 554–559.CrossRefGoogle ScholarPubMed
8.Spielberg, SP., Gordon, GB., Blake, DA., et al. Predisposition to phenytoin hepatotoxicity assessed in vitro. N Engl J Med 1981; 305: 722–727.CrossRefGoogle ScholarPubMed
9.Gerson, WT., Fine, DF., Speilberg, SP., Sensenbrenner, LL.Anticonvulsant-induced aplastic anemia: increased susceptibility to toxic drug metabolites in vitro. Blood 1983; 61: 889–893.CrossRefGoogle ScholarPubMed
10.Dreifus, F., Santilli, N., Langer, DH., et al. Valproic acid hepatic fatalities: a retrospective review. Neurology 1987; 37: 379–385.CrossRefGoogle Scholar
11.Huttenlocker, PR., Solitare, GB., Adams, G.Infantile diffuse cerebral degeneration with hepatic cirrhosis. Arch Neurol 1976; 33: 186–190.CrossRefGoogle Scholar
12.Scheffner, D., Konig, S., Rauterberg-Ruland, I., et al. Fatal liver failure in 16 children with valproate therapy. Epilepsia 1988; 29: 530–542.CrossRefGoogle ScholarPubMed
13.Fenichel, FM.Valproate hepatotoxicity: two new cases, a summary of others and recommendations. Pediatr Neurol 1985; 1: 109–113.CrossRefGoogle Scholar
14.Delattre, JT., Safai, B., Posner, JB.Erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and phenytoin. Neurology 1988; 38: 194–197.CrossRefGoogle ScholarPubMed
15.Camfield, CS., Camfield, PR., Smith, E., Tibbies, JAR.Asymptomatic children with epilepsy: little benefit from screening for anticonvulsant-induced liver, blood or renal damage. Neurology 1986; 36:838–841.CrossRefGoogle ScholarPubMed
16.Mattson, RH., Cramer, JA., Collins, JF., et al. Comparison of carbamazepine, phenobarbital, phenytoin and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985; 313: 145–151.CrossRefGoogle ScholarPubMed
17.Camfield, PR., Camfield, CS., Dooley, JM., et al. Routine screening of blood and urine for severe reactions to anticonvulsant drugs in asymptomatic patients is of doubtful value. Can Med Assoc J 1989; 140: 1303–1305.Google ScholarPubMed
18.Camfield, PR., Camfield, CS., Dooley, JM., et al. Routine screening of blood and urine for severe anticonvulsant reactions in asymptomatic patients is of doubtful value. Can J Neurol Sci 1989: 16; 361–364.CrossRefGoogle Scholar
19.Murphy, JM., Mashman, J., Miller, JD., Bell, JB.Suppression of carbamazepine-induced rash with prednisone. Neurology 1991; 41: 144–145.CrossRefGoogle ScholarPubMed
20.Smith, H., Newton, R.Adverse reactions to carbamazepine managed by desensitization (letter) Lancet 1985; 1: 753.CrossRefGoogle Scholar
21.Eames, P.Adverse reactions to carbamazepine managed by desensitization (letter) Lancet 1989; 1: 509–510.CrossRefGoogle Scholar
22.Purvis, SJ., Hashimoto, SA., Tse, KS.Successful desensitization of patients with carbamazepine allergy. Can J Neurol Sci 1988: 15; 237(abstract).Google Scholar
23.Dreifuss, FE.Valproate: toxicity. In: Levy, RH., Mattson, RH., Meldrum, BS., Penry, JK., Dreifuss, FE., eds. Antiepileptic Drugs. 3rd ed. New York, NY: Raven Press, 1989: 643–651.Google Scholar
24.Silverstein, FS., Parrish, MA., Johnston, MV.Adverse behavioural reactions in children treated with carbamazepine (Tegretol). J Pediatr 1982; 101:785–787.CrossRefGoogle ScholarPubMed
25.Camfield, CS., Chaplin, S., Doyle, AB., et al. Side effects of phenobarbital in toddlers: behavioural and cognitive aspects. J Pediatr 1979;95:361–366.CrossRefGoogle ScholarPubMed
26.Sheth, RD., Goulden, KJ., Penney, S., Ronen, GM.Treatment of epilepsy with clobazam: a 5-year cohort study in children. Ann Neurol 1993: 34; 449 (abstract).Google Scholar
27.Grant, SM., Heel, RC.Vigabatrin: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in epilepsy and disorders of motor control. Drugs 1991; 41: 889–926.CrossRefGoogle ScholarPubMed
28.Reynolds, EH.Gamma vinyl GABA (vigatrin): clinical experience in adult and adolescent patients with intractable epilepsy. Epilepsia 1992; 33 (Suppl 5): S30–S33.Google ScholarPubMed
29.Reynolds, EH.Chronic antiepileptic toxicity: a review. Epilepsia 1975; 16: 319–352.CrossRefGoogle ScholarPubMed
30.Dongari, A., McDonnell, HT., Langais, RP.Drug-induced gingival overgrowth. Oral Surg Oral Med Oral Pathol 1993; 76: 543–548.CrossRefGoogle ScholarPubMed
31.Churesigaew, S., Ruvalcaba, RH., Kelley, VC.Epilepsy and abnormal calcium metabolism in institutionalized mentally retarded patients. Am J Ment Defic 1975; 79: 738–741.Google ScholarPubMed
32.Camfield, CS., Delvin, EE., Camfield, PR., and Glorieux, FH.Normal serum 25-hydroxyvitamin D levels in phenobarbital-treated toddlers. Dev Pharmacol Ther 1983; 6: 157–161.CrossRefGoogle ScholarPubMed
33.Shorvon, SD., Reynolds, EH.Anticonvulsant peripheral neuropathy: a clinical and electrophysiological study of patients on single drug treatment with phenytoin, carbamazepine, or barbiturates. J Neurol Neurosurg Psychiatry 1982; 45: 620–626.CrossRefGoogle ScholarPubMed
34.McLain, LW., Martin, JT., Allen, JH.Cerebellar degeneration due to chronic phenytoin therapy. Ann Neurol 1980; 7: 18–23.CrossRefGoogle ScholarPubMed
35.Masur, H., Elger, DE., Ludolph, AC., Galanski, M.Cerebellar atrophy following acute intoxication with phenytoin. Neurology 1989; 39: 432–433.CrossRefGoogle ScholarPubMed
36.Lindvall, O., Nilsson, B.Cerebellar atrophy following phenytoin intoxication. Ann Neurol 1984; 16: 258–260.CrossRefGoogle ScholarPubMed