Barbiturates

Barbiturates

The major pharmacologic action of barbiturates is to reduce over-all CNS alertness. Barbiturates used primarily as sedatives and hypnotics include:

·                 amobarbital

·                 butabarbital

·                 mephobarbital

·                 pentobarbital

·                 phenobarbital

·                 secobarbital.

On the dose

Low doses of barbiturates depress the sensory and motor cortex in the brain, causing drowsiness. High doses may cause respirato-ry depression and death because of their ability to depress all lev-els of the CNS.

Pharmacokinetics

Barbiturates are well absorbed from the GI tract, distributed rapidly, metabolized by the liver, and excreted in urine.

Pharmacodynamics

As sedative-hypnotics, barbiturates depress the sensory cortex of the brain, decrease motor activity, alter cerebral function, and pro-duce drowsiness, sedation, and hypnosis.

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These drugs appear to act throughout the CNS; however, the RAS of the brain, which is responsible for wakefulness, is a particularly sensitive site.

Pharmacotherapeutics

Barbiturates have many clinical indications, including:

·                 daytime sedation (for short periods only, typically less than 2 weeks)

·                 hypnotic effects for patients with insomnia

·                 preoperative sedation and anesthesia

·                 relief of anxiety

·                 anticonvulsant effects.

Popularity plunge

Patients develop tolerance to barbiturates more quickly than to benzodiazepines, and physical dependence on barbiturates may occur even with a small daily dosage. In comparison, benzodiazepines are relatively effective and safe and, for these reasons,have replaced barbiturates as the sedatives and hypnotics of choice.

Drug interactions

Barbiturates may interact with many other drugs:

• They may reduce the effects of beta-adrenergic blockers (metoprolol, propranolol), chloramphenicol, corticosteroids, doxycy cline, oral anticoagulants, hormonal contraceptives, quinidine, tricyclic antidepressants (TCAs), metronidazole, theophylline,and cyclosporine.

• Hydantoins, such as phenytoin, reduce the metabolism of phenobarbital, resulting in increased toxic effects.

• Their use with methoxyflurane may stimulate production of metabolites that are toxic to the kidneys.

• Their use with other CNS depressants (especially alcohol) may cause excessive CNS depression.

• Valproic acid may increase barbiturate levels.

• Monoamine oxidase inhibitors (MAOIs) inhibit the metabolismof barbiturates, increasing their sedative effects.

• When barbiturates are taken with acetaminophen, the risk ofliver toxicity increases. (See Adverse reactions to barbiturates.)