Absence seizures Antiseizure drugs

Other antiseizure drugs regulate a subset of voltagegated calcium currents. In contrast to partial seizures, which arise from localized regions of the cerebral cortex, the absence or petit mal form of generalized-onset seizures arise from the reciprocal firing of the thalamus and... 

Trimethadione, the first oxazolidinedione (Figure 24-3), was introduced as an antiseizure drug in 1945 and remained the drug of choice for absence seizures until the introduction of succinimides in the 1950s. Use of the oxazolidinediones (trimethadione, paramethadione, and dimethadione) is now very limited. 

Withdrawal Withdrawal from antiseizure drugs should be accomplished gradually to avoid increased seizure frequency and severity. In general, withdrawal from anti-absence drugs is more easily accomplished than withdrawal from drugs used in partial or generalized tonic-clonic seizure states. 

Drug of choice in absence seizures Is established to be teratogenic in humans Life-threatening skin disorders may occur Visual field defects occur in up to one-third of patients Withdrawal of antiseizure drugs can cause increased seizure frequency and severity. Withdrawal is least likely to be a problem with (A) Clonazepam Diazepam Ethosuximide Phenobarbital Phenytoin... 

Three of the drugs listed are effective in absence seizures. Ethosuximide and valproic acid are not sedating, and tolerance does not develop to their antiseizure activity. Clonazepam is effective but exerts troublesome CNS depressant effects, and tolerance develops with chronic use. At high doses, the drug has a dependence liability like most benzodiazepines. The answer is (A). 

There are two problems with regard to withdrawal from antiseizure drugs the effects of withdrawal itself and the need to continue suppression of seizures. Dose-tapering is an important principle in antiseizure drug withdrawal. As a rule, withdrawal from drugs used in absence seizures is easier than withdrawal from drugs used for partial and tonic-clonic seizures. Withdrawal is most difficult in patients who have been treated with barbiturates and benzodiazepines. The answer is (C). 

Because oxazolidinediones are toxic, an extensive search was undertaken to replace them with less toxic drugs. Substituting the ring O in the oxazolidinediones with a methylene group gave the antiseizure succinimides. The clinically used succinimides include ethosuximide, methsuximide, and phensuximide, which were introduced between 1951 and 1958 (Fig. 20.11) and widely accepted for the treatment of absence seizures. 

Phensuximide and methsuximide are phenylsuccinimides that were developed and marketed before ethosuximide. They are used primarily as anti-absence drugs. Methsuximide is generally considered more toxic, and phensuximide less effective, than ethosuximide. Unlike ethosuximide, these two compounds have some activity against maximal electroshock seizures, and methsuximide has been used for partial seizures by some investigators. The desmethyl metabolite of methsuximide has a half-life of 25 hours or more and exerts the major antiseizure effect. The toxicity and reduced effectiveness of phensuximide when compared with methsuximide has been investigated, and the failure of the desmethyl metabolite to accumulate in the former probably explains its relatively... 

Phenobarbital has selective antiseizure activity at low doses and has a long half-life suitable for maintenance treatment in seizure disorders (for characteristics of barbiturates, see sedative-hypnotics). Clonazepam is usually a backup drug in absence and myoclonic seizures it causes marked sedation at anticonvulsant doses. IV lorazepam and diazepam are both used in status epilepticus. 

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