May 27, 2017
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Phenobarbital is capable of producing all levels of CNS mood alteration, from excitation to mild sedation to hypnosis, and deep coma. Overdosage can produce death. In high enough therapeutic doses, Phenobarbital induces anesthesia. Phenobarbital depresses the sensory cortex, decreases motor activity, alters cerebellar function, and produces drowsiness, sedation, and hypnosis. Phenobarbital-induced sleep differs from physiological sleep. Sleep laboratory studies have demonstrated that Phenobarbital reduces the amount of time spent in the rapid eye movement (REM) phase of sleep or the dreaming stage. Also Stages III and IV sleep are decreased. Following abrupt cessation of Phenobarbital used regularly, patients may experience markedly increased dreaming, nightmares and/or insomnia. Therefore, withdrawal of a single therapeutic dose over 5 or 6 days has been recommended to lessen the REM rebound and disturbed sleep which contribute to drug withdrawal syndrome (for example, decrease the dose from 3 to 2 doses a day for 1 week).

Phenobarbital might be expected to lose its effectiveness for inducing and maintaining sleep after about 2 weeks.

Phenobarbital has little analgesic action at subanesthetic doses. Rather, in subanesthetic doses, this drug may increase the reaction to painful stimuli. All barbiturates exhibit anticonvulsant activity in anesthetic doses. However, of the drugs in this class, only phenobarbital, mephobarbital, and metharbital are effective as oral anticonvulsants in subhypnotic doses.

Phenobarbital is a respiratory depressant. The degree of respiratory depression is dependent upon the dose. With hypnotic doses, respiratory depression produced by Phenobarbital is similar to that which occurs during physiologic sleep with slight decrease in blood pressure and heart rate. Studies in laboratory animals have shown that Phenobarbital causes reduction in the tone and contractility of the uterus, ureters, and urinary bladder. However, concentrations of the drug required to produce this effect in humans are not reached with sedative-hypnotic doses.

Phenobarbital does not impair normal hepatic function but has been shown to induce liver microsomal enzymes, thus increasing and/or altering the metabolism of barbiturates and other drugs. (See DRUG INTERACTIONS.)


Phenobarbital is absorbed in varying degrees following oral, rectal or parenteral administration. The salts are more rapidly absorbed than are the acids. The rate of absorption is increased if the sodium salt is ingested as a dilute solution or taken on an empty stomach.

Duration of action, which is related to the rate at which phenobarbital is redistributed throughout the body varies among persons and in the same person from time to time. Long-acting phenobarbital has onset of action of 1 hour or longer and duration of actions of 10 to 12 hours.

No studies have demonstrated that the different routes of administration are equivalent with respect to bioavailability.

Phenobarbital is a weak acid that is absorbed and rapidly distributed to all tissues and fluids with high concentrations in the brain, liver, and kidneys. The more lipid soluble the drug is, the more rapidly it penetrates all tissues of the body.

Phenobarbital has the lowest lipid solubility, lowest plasma binding, lowest brain protein binding, the longest delay in onset of activity, and the longest duration of action in the barbiturate class.

Phenobarbital has a plasma half-life of 53 to 118 hours (mean: 79 hours). For children and newborns the plasma half-life is 60 to 180 hours (mean: 110 hours). (Half-life values were determined for newborn age being defined as 48 hours or less.)

Phenobarbital is metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine, and less commonly, in the feces. Approximately 25 to 50 percent of a dose of phenobarbital is eliminated unchanged in the urine, whereas the amount of other barbiturates excreted unchanged in the urine is negligible. The excretion of unmetabolized barbiturate is one feature that distinguishes the long-acting category from those belonging to other categories which are almost entirely metabolized. The inactive metabolites of the barbiturates are excreted as conjugates of glucuronic acid.

Last reviewed on RxList: 1/17/2017
This monograph has been modified to include the generic and brand name in many instances.

Phenobarbital - User Reviews

Phenobarbital User Reviews

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