Benzodiazepines

Benzodiazepines

The four benzodiazepine drugs that provide anticonvulsant ef-fects are:

clonazepam

·                 clorazepate

·                 diazepam (parenteral form)

·                 lorazepam. (See Sound-alikes: Diazepam and lorazepam.)

Only one for ongoing treatment

Only clonazepam is recommended for long-term treatment of epilepsy. Diazepam may be used to treat status epilepticus or, in rectal form, repetitive seizures. Lorazepam I.V. is considered the drug of choice for status epilepticus. Clorazepate is prescribed as an adjunct in treating partial seizures.

Pharmacokinetics

The patient can receive benzodiazepines orally, parenterally or, in special situations, rectally (diazepam rectal gel).

Absorption and distribution

Benzodiazepines are absorbed rapidly and almost completely from the GI tract but are distributed at different rates. Protein binding of benzodiazepines ranges from 85% to 90%.

Metabolism and excretion

Benzodiazepines are metabolized in the liver to multiple metabo-lites and are then excreted in urine. They readily cross the placen-ta and are secreted in breast milk.

Pharmacodynamics

Benzodiazepines act as:

·                 anticonvulsants

·                 antianxiety agents

·                 sedative-hypnotics

·                 muscle relaxants.

Their mechanism of action is poorly understood.

Pharmacotherapeutics

Each of the benzodiazepines can be used in slightly different ways.

Absence, atypical, and more

Clonazepam is used to treat the following types of seizures:

·                 absence (petit mal)

·                 atypical absence (Lennox-Gastaut syndrome)

·                 atonic

·                 myoclonic.

I.V. or with others

Diazepam isn’t recommended for long-term treatment because of its potential for addiction and the high serum concentra-tions required to control seizures.

I.V. lorazepam is currently considered the benzodi-azepine of choice for treating status epilepticus.

I.V. diazepam is used to control status epilepticus. Be-cause diazepam provides only short-term effects of less than 1 hour, the patient must also be given a long-acting anticonvulsant, such as phenytoin or phenobarbital, dur-ing diazepam therapy. Diazepam rectal gel is approved for treatment of repetitive seizures and has reduced the incidence of recurrent seizures in children.

Clorazepate is used with other drugs to treat partial seizures.

Drug interactions

When benzodiazepines are taken with CNS depressants, sedatives, cimetidine, or hormonal contraceptives, depressant effects are en-hanced. This can cause motor skill impairment, respiratory de-pression, excessive sedation, CNS depression, and even death at high doses. (See Adverse reactions to benzodiazepines.)