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Chapter 24: Antiseizure Drugs

A 9-year-old child is having learning difficulties at school. He has brief lapses of awareness with eyelid fluttering that occur every 5–10 min. Electroencephalogram (EEG) studies reveal brief 3-Hz spike and wave discharges appearing synchronously in all leads. Which drug would be effective in this child without the disadvantages of excessive sedation or tolerance development?

(A) Clonazepam

(B) Diazepam

(C) Ethosuximide

(D) Gabapentin

(E) Phenobarbital

This child suffers from absence seizures, and 2 of the drugs listed are effective in this seizure disorder. Clonazepam is effective but exerts troublesome CNS-depressant effects, and tolerance develops with chronic use. Ethosuximide is not excessively sedating, and tolerance does not develop to its antiseizure activity. Valproic acid (not listed) is also used in absence seizures. The answer is C.

Which statement concerning the proposed mechanisms of action of anticonvulsant drugs is most accurate?

(A) Benzodiazepines facilitate glutamate-mediated inhibitory actions

(B) Ethosuximide selectively blocks potassium ion (K+) channels in thalamic neurons

(C) Phenobarbital produces a selective blockade of calcium ion (Ca2+) channels

(D) Phenytoin prolongs the inactivated state of the Na+ channel

(E) Zonisamide blocks voltage-gated K+ channels

Benzodiazepines facilitate GABA-mediated inhibitory actions. Ethosuximide selectively blocks calcium channels in thalamic neurons. Phenobarbital produces multiple effects, mainly enhancement of GABA-chloride inhibitory activity. Zonisamide blocks voltage-gated Na+ channels. Phenytoin selectively blocks the Na+ channel and prolongs the inactivated state. The answer is D.

Which drug used in management of seizure disorders is most likely to elevate the plasma concentration of other drugs administered concomitantly?

(A) Carbamazepine

(B) Clonazepam

(C) Phenobarbital

(D) Phenytoin

(E) Valproic acid

Read the question carefully. Several of these agents (carbamazepine, phenobarbital, and phenytoin) induce drug metabolizing enzymes and reduce the plasma concentration of other drugs. Valproic acid, an inhibitor of drug metabolism, can increase the plasma levels of many drugs, including those used in seizure disorders such as carbamazepine, lamotrigine, phenobarbital, and phenytoin. Benzodiazepines (including clonazepam and diazepam) as well as gabapentin and vigabatrin have no major effects on the metabolism of other drugs. The answer is E.

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