Phenobarbital Sodium

PHENOBARBITAL SODIUM- phenobarbital sodium injection

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The barbiturates are nonselective central nervous system (CNS) depressants which are primarily used as sedative hypnotics and also anticonvulsants in subhypnotic doses. The barbiturates and their sodium salts are subject to control under the Federal Controlled Substances Act (CIV).

Barbiturates are substituted pyrimidine derivatives in which the basic structure common to these drugs is barbituric acid, a substance which has no central nervous system activity. CNS activity is obtained by substituting alkyl, alkenyl or aryl groups on the pyrimidine ring.

Phenobarbital Sodium Injection, USP is a sterile solution for intramuscular or slow intravenous administration as a long-acting barbiturate. Each mL contains phenobarbital sodium either 65 mg or 130 mg, alcohol 0.1 mL, and propylene glycol 0.678 mL in Water for Injection; hydrochloric acid added, if needed, for pH adjustment. The pH range is 9.2-10.2. Contains no preservative.

Chemically, phenobarbital sodium is 2,4,6(1 H ,3 H ,5 H)-Pyrimidinetrione,5-ethyl-5-phenyl-, monosodium salt and has the following structural formula:

Structural formula

C 12 H 11 N 2 NaO 3 MW 254.22

The sodium salt of phenobarbital occurs as a white, slightly bitter powder, crystalline granules or flaky crystals; it is soluble in alcohol and practically insoluble in ether or chloroform.


Barbiturates are 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, barbiturates induce anesthesia.

Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function and produce drowsiness, sedation and hypnosis.

Barbiturate-induced sleep differs from physiological sleep. Sleep laboratory studies have demonstrated that barbiturates reduce the amount of time spent in the rapid eye movement (REM) phase of sleep or dreaming stage. Also, Stages III and IV sleep are decreased. Following abrupt cessation of barbiturates 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).

In studies, secobarbital sodium and pentobarbital sodium have been found to lose most of their effectiveness for both inducing and maintaining sleep by the end of 2 weeks of continued drug administration even with the use of multiple doses. As with secobarbital sodium and pentobarbital sodium, other barbiturates might be expected to lose their effectiveness for inducing and maintaining sleep after about 2 weeks. The short-, intermediate- and, to a lesser degree, long-acting barbiturates have been widely prescribed for treating insomnia. Although the clinical literature abounds with claims that the short-acting barbiturates are superior for producing sleep while the intermediate-acting compounds are more effective in maintaining sleep, controlled studies have failed to demonstrate these differential effects. Therefore, as sleep medications, the barbiturates are of limited value beyond short-term use.

Barbiturates have little analgesic action at subanesthetic doses. Rather, in subanesthetic doses these drugs may increase the reaction to painful stimuli. All barbiturates exhibit anticonvulsant activity in anesthetic doses.

Barbiturates are respiratory depressants by virtue of their direct effect on the medullary respiratory center. They diminish and, in high doses, may abolish the sensitivity of the respiratory center to its normal stimulus, carbon dioxide. The degree of respiratory depression is dependent upon dose. With hypnotic doses, respiratory depression produced by barbiturates is similar to that which occurs during physiologic sleep with slight decrease in blood pressure and heart rate.

Ordinary hypnotic doses of barbiturates have no significant effect on the cardiovascular system. The barbiturates tend to decrease the tonus of the gastrointestinal musculature. They have no direct injurious effect on the normal kidney. Severe oliguria or anuria may occur in acute barbiturate poisoning, largely as a result of the marked hypotension.

Hypnotic doses tend to reduce slightly the metabolic rate in man. Body temperature is reduced slightly, owing to lessened activity and to depression of the central temperature-regulatory mechanisms.

While anesthetic doses of all barbiturates exert an anticonvulsant effect, phenobarbital has a selective anticonvulsant activity independent of the degree of sedation produced. Phenobarbital limits the spread of seizures and raises the seizure threshold in grand mal (generalized tonic-clonic) epilepsy.

Studies in laboratory animals have shown that barbiturates cause reduction in the tone and contractility of the uterus, ureters and urinary bladder. However, concentrations of the drugs required to produce this effect in humans are not reached with sedative-hypnotic doses.

Barbiturates do not impair normal hepatic function, but have been shown to induce liver microsomal enzymes, thus increasing and/or altering the metabolism of barbiturates and other drugs. (See PRECAUTIONS, Drug Interactions.)

Following IV administration, the onset of action is 5 minutes for phenobarbital sodium. For IM administration, the onset of action is slightly slower. Maximal CNS depression may not occur until 15 minutes or more after IV administration.

Duration of action, which is related to the rate at which the barbiturates are redistributed throughout the body, varies among persons and in the same person from time to time.

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

Barbiturates are weak acids that are absorbed and rapidly distributed to all tissues and fluids with high concentrations in the brain, liver and kidneys. Lipid solubility of the barbiturates is the dominant factor in their distribution within the body. The more lipid soluble the barbiturate, the more rapidly it penetrates all tissues of the body. Barbiturates are bound to plasma and tissue proteins to a varying degree with the degree of binding increasing directly as a function of lipid solubility.

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. Its diffusion across the blood-brain barrier and its distribution into other tissues occurs more slowly than with other short-acting barbiturates. Fifteen minutes or more may be required for maximal central depression following intravenous administration of phenobarbital. However, with time, phenobarbital distributes into all tissues and fluids. Barbiturates are known to cross the placenta. Phenobarbital is 20-45% protein bound. In adults, the plasma half-life of phenobarbital is 53 to 118 hours (mean 79 hours) and in children/newborns, the plasma half-life is 60 to 180 hours (mean 110 hours).

Barbiturates are 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. Urinary pH and rate of urine flow affect the renal circulation of unchanged phenobarbital, a greater quantity being eliminated in alkaline urine and at increased flow rates. 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.



  1. Sedative. Sedation is obtainable within an hour, and in adequate dosage, the duration of action is more than six hours. Included in the more common conditions in which the sedative action of this class of drugs is desired are anxiety-tension states, hyperthyroidism, essential hypertension, nausea and vomiting of functional origin, motion sickness, acute labyrinthitis, pylorospasm in infants, chorea and cardiac failure. Phenobarbital is also a useful adjunct in treatment of hemorrhage from the respiratory or gastrointestinal tract. Phenobarbital controls anxiety, decreases muscular activity and lessens nervous excitability in hyperthyroid patients. However, thyrotoxic individuals occasionally react poorly to barbiturates.
  2. Hypnotic, for the short-term treatment of insomnia, since it appears to lose its effectiveness for sleep induction and sleep maintenance after 2 weeks (see CLINICAL PHARMACOLOGY).
  3. Preanesthetic.
  4. Long-term anticonvulsant, (phenobarbital, mephobarbital and metharbital) for the treatment of generalized tonic-clonic and cortical focal seizures. And, in the emergency control of certain acute convulsive episodes, e.g., those associated with status epilepticus, cholera, eclampsia, cerebral hemorrhage, meningitis, tetanus, and toxic reactions to strychnine or local anesthetics. Phenobarbital sodium may be administered intramuscularly or intravenously as an anticonvulsant for emergency use. When administered intravenously, it may require 15 or more minutes before reaching peak concentrations in the brain. Therefore, injecting phenobarbital sodium until the convulsions stop may cause the brain level to exceed that required to control the convulsions and lead to severe barbiturate-induced depression.
  5. Phenobarbital is indicated in pediatric patients as an anticonvulsant and as a sedative, including its preoperative and postoperative use.

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