The barbiturates are nonselective central nervous system 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 (See “Drug Abuse and Dependence” section).

The sodium salts of amobarbital, pentobarbital, phenobarbital, and secobarbital are available as sterile parenteral solutions.

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 (CNS) activity. CNS activity is obtained by substituting alkyl, alkenyl, or aryl groups on the pyrimidine ring.

NEMBUTAL Sodium Solution (pentobarbital sodium injection) is a sterile solution for intravenous or intramuscular injection. Each mL contains pentobarbital sodium 50 mg, in a vehicle of propylene glycol, 40%, alcohol, 10% and water for injection, to volume. The pH is adjusted to approximately 9.5 with hydrochloric acid and/or sodium hydroxide.

NEMBUTAL Sodium is a short-acting barbiturate, chemically designated as sodium 5-ethyl-5-(1-methylbutyl) barbiturate. The structural formula for pentobarbital sodium is:

Nembutal – Clinical Pharmacology

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 at fixed doses. 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. However, of the drugs in this class, only phenobarbital, mephobarbital, and metharbital have been clinically demonstrated to be effective as oral anticonvulsants in subhypnotic doses.

Barbiturates are respiratory depressants. 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.

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” section).

Pharmacokinetics:

Uses of Nembutal:

• It is used to treat sleep problems.
• It is used to calm you before a procedure.
• It is used to treat seizures.
• It is used to put you to sleep for surgery.
• It may be given to you for other reasons. Talk with the doctor.

What do I need to tell my doctor BEFORE I take Nembutal?

• If you have an allergy to pentobarbital or any other part of Nembutal (pentobarbital).
• If you are allergic to Nembutal (pentobarbital); any part of Nembutal (pentobarbital); or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you have ever had porphyria.
• If you have liver disease.

This is not a list of all drugs or health problems that interact with Nembutal (pentobarbital).

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Nembutal (pentobarbital) with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take Nembutal?

• Tell all of your health care providers that you take Nembutal (pentobarbital). This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until the effects of Nembutal (pentobarbital) wear off and you feel fully awake.
• Have your blood work checked if you are on Nembutal (pentobarbital) for a long time. Talk with your doctor.
• This medicine may be habit-forming with long-term use.
• Use Nembutal (pentobarbital) for short periods of time. If signs show up again, talk with the doctor.
• If you have been taking Nembutal (pentobarbital) on a regular basis and you stop it all of a sudden, you may have signs of withdrawal. Do not stop taking Nembutal (pentobarbital) all of a sudden without calling your doctor. Tell your doctor if you have any bad effects.
• Avoid drinking alcohol while taking Nembutal (pentobarbital).
• Talk with your doctor before you use other drugs and natural products that slow your actions.
• If you are 65 or older, use Nembutal (pentobarbital) with care. You could have more side effects.
• Studies in young animals and children have shown that frequent or long-term use of anesthesia drugs or drugs used for sleep in children younger than 3 years of age may lead to long-term brain problems. This may also happen in unborn babies if the mother uses Nembutal (pentobarbital) during the third trimester of pregnancy. Talk with the doctor.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking Nembutal (pentobarbital).
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking Nembutal (pentobarbital), call your doctor right away.
• Long-term use of Nembutal (pentobarbital) during pregnancy may cause dependence in the unborn baby or newborn. Talk with the doctor.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is this medicine (Nembutal) best taken?

Use Nembutal (pentobarbital) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a muscle or vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

For all uses of Nembutal (pentobarbital):

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Trouble breathing, slow breathing, or shallow breathing.
• Very bad dizziness or passing out.
• Feeling nervous and excitable.
• Feeling confused.
• Low mood (depression).

Injection (if given in the muscle):

• Pain and irritation where  (pentobarbital) goes into the body.

Injection (if given in the vein):

This medicine may cause tissue damage if the drug leaks from the vein. Tell your nurse if you have any redness, burning, pain, swelling, blisters, skin sores, or leaking of fluid where the drug is going into your body.

of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of these findings is not clear. However, based on the available data, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately three years of age in humans (see “Precautions-Pregnancy and Pediatric Use” and “Animal Pharmacology and/or Toxicology”).

Some published studies in children suggest that similar deficits may occur after repeated or prolonged exposures to anesthetic agents early in life and may result in adverse cognitive or behavioral effects. These studies have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors such as the surgery or underlying illness.

Anesthetic and sedation drugs are a necessary part of the care of children and pregnant women needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks