Anticonvulsants, or antiepileptics, are used to treat acute seizures and prevent convulsions in patients with epilepsy. The first generation of antiepileptics was developed between 1938 and 1978 (Table 197-1). Since 1993, over 20 additional agents, termed the second and third generations of antiepileptic drugs, have been introduced into clinical use. In general, these new anticonvulsants have fewer serious adverse side effects and fewer drug interactions than the first-generation agents.
TABLE 197-1First-Generation Anticonvulsant Drugs ||Download (.pdf) TABLE 197-1 First-Generation Anticonvulsant Drugs
|Drug ||Typical Oral Adult Dose (milligrams) ||Maximum Oral Daily Dose (milligrams) ||Elimination Half-Life With Therapeutic Doses (h) |
|Carbamazepine ||800–1200 per day divided BID to QID ||1600 || |
25–65 (initial doses)
12–17 (repeated doses)
|Ethosuximide ||250–750 BID ||1500 ||56–60 |
|Methsuximide ||300–1200 once daily ||1200 || |
1–3 (parent drug)
28–34 (active metabolite)
|Phenobarbital ||60 BID or TID ||200* ||79 |
|Phenytoin ||300–400 per day divided BID or TID ||600* ||7–42 |
|Primidone ||250 TID or QID ||2000 || |
10–12 (parent drug)
|Valproic acid ||30–60 per kilogram per day divided BID or TID ||60 per kilogram ||16 |
The first-generation drugs have an established therapeutic range for serum levels that can guide therapy during long-term management and that roughly correlate with acute toxicity from an overdose. Consistent therapeutic levels have not been established for the second- and third-generation anticonvulsants, and serum levels are not a useful guide to therapy.
The toxicity of two benzodiazepines used to treat seizures—clonazepam and clobazam—is discussed elsewhere (see Chapter 183, “Benzodiazepines”)
This chapter reviews the pharmacology, clinical features, and treatment for toxicity of commonly used anticonvulsants. Disposition recommendations depend on the resolution of clinical toxicity, but patients with intentional overdose need mental health evaluation in the ED before discharge.
PHENYTOIN AND FOSPHENYTOIN
Phenytoin is a primary anticonvulsant for partial and generalized tonic-clonic seizures. In conjunction with rapidly acting anticonvulsants, it is useful in the treatment of non–drug-induced status epilepticus.1 Phenytoin has been used to prevent seizures due to head trauma (in the immediate posttraumatic period) and in the management of some chronic pain syndromes. Serious complications are extremely rare after intentional phenytoin overdose if supportive care is provided. Most phenytoin-related deaths have been associated with rapid IV administration or hypersensitivity reactions.
Phenytoin is available in oral and injectable forms. Phenytoin has poor solubility in water, so the vehicle for the parenteral formulation is 40% propylene glycol and 10% ethanol, adjusted to a pH of 12 with sodium hydroxide. The acute cardiovascular toxicity seen with IV phenytoin infusion is usually ascribed to the propylene glycol diluent. Other limitations with parenteral phenytoin are the irritating nature of the vehicle and ...