Antiseizure drugs barbiturate

Until 1990, approximately 16 antiseizure drugs were available, and 13 of them can be classified into five very similar chemical groups barbiturates. 

Aside from the bromides, phenobarbital is the oldest of the currently available antiseizure drugs. Although it has long been considered one of the safest of the antiseizure agents, the use of other medications with lesser sedative effects has been urged. Many consider the barbiturates the drugs of choice for seizures only in infants. 

The four derivatives of barbituric acid clinically useful as antiseizure drugs are phenobarbital, mephobarbital, metharbital, and primidone. The first three are so similar that they are considered together. Metharbital is methylated barbital, and mephobarbital is methylated phenobarbital both are demethylated in vivo. The pKas of these three weak acid compounds range from 7.3 to 7.9. Slight changes in the normal acid-base balance, therefore, can cause significant fluctuation in the ratio of the ionized to the un-ionized species. This is particularly important for phenobarbital, the most commonly used barbiturate, whose pKa is similar to the plasma pH of 7.4. 

Most of the sedative-hypnotics are capable of inhibiting the development and spread of epileptiform activity in the central nervous system. Some selectivity exists in that some members of the group can exert anticonvulsant effects without marked central nervous system depression (although psychomotor function may be impaired). Several benzodiazepines—including clonazepam, nitrazepam, lorazepam, and diazepam—are sufficiently selective to be clinically useful in the management of seizure states (see Chapter 24 Antiseizure Drugs). Of the barbiturates, phenobarbital and metharbital (converted to phenobarbital in the body) are effective in the treatment of generalized tonic-clonic seizures. 

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). 

Amphetamine (Benzedrine). Amphetamine was synthesized in 1887. It was quickly found to be a potent stimulant with effects similar to cocaine, which had been discovered over 100 years before. In the subsequent years, amphetamine found a variety of uses. It was used to treat narcolepsy, Parkinson s disease, barbiturate overdose, bed wetting (enuresis), and obesity. It was also used to counteract the sedating effects of other drugs and medications including antiseizure medications and alcohol. 

Mechanism of Action. Barbiturates are known to increase the inhibitory effects of GABA (see Chapter 6), and this effect is probably the primary way that these drugs decrease seizure activity. Barbiturates may also produce some of their antiseizure effects by inhibiting calcium entry into excitatory presynaptic nerve terminals and thereby decreasing the release of excitatory neurotransmitters such as glutamate.20... 

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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