Butabarbital

It is most often administered orally as either sodium solution or tablet, however can also be given by intravenous injection. Tablets contain either 30 mg or 50 mg of butabarbital sodium, or 30 mg/5mL with 7% alcohol/vol in solution. For preoperative sedation, adults are administered 50–100 mg 60-90min prior to surgery, with varying doses for pediatric and geriatric patients.[11]

Effects from oral doses often are felt within an hour of administration, lasting somewhere from six to eight hours in effect.[9] A non-selective depressant of the CNS, Butabarbital sodium is used as a sedative hypnotic, depending on dose, to induce drowsiness or sleep, or reduce anxiety and tension.[12] Butabarbital sodium can be used as a pre-surgical anesthetic aid or in the short-term treatment of sleep and anxiety disorders. For short term sleep maintenance and induction butabarbital sodium treatment is recommended to be limited to two weeks, after which it begins to lose efficacy.[12] The half life is approximately 100hrs, eliminated primarily by hepatic microsomal enzymes and excreted in the urine.

Butabarbital sodium is a Schedule III controlled substance in the US and Canada due to risk of abuse and dependence. A psychoactive substance, butabarbital drugs are often abused with risk of acute intoxication and addiction. Barbiturates such as butabarbital are thought to be habit-forming and addictive, and have severe risks from withdrawal including death.[12] Due to the high risk of dependence and overdose, use of butabarbital is highly regulated and has become less common in clinical application.

[11]

1-10%

• Somnolence

<1%

Those with a hypersensitivity to barbiturates or a history of porphyria should discuss with a doctor before using butisol sodium treatment. Butabarbital has also been shown to interact with some medicines; Talk to your doctor if taking Monoamine oxidase inhibitors (MAOIs), beta-blockers, oral-contraceptives, or other medications, as their efficacy may be affected.[13]

At low doses Butabarbital has been shown clinically to induce drowsiness, depressing the sensory cortex and motor activity. In some rare cases Butabarbital has been shown to produce small bursts of excitement or euphoria prior to the sedative effects. Butabarbital is a highly potent drug however, with addictive properties, and small variations in dose can result in significant escalation of effects.[14]

Butabarbituates are rapidly distributed and absorbed in the brain, liver and kidneys. One of the more lipophilic barbiturates, butabarbital crosses the blood brain barrier with relative ease, and is slightly more potent then other less lipophilic barbiturates such as phenobarbital.[14] Butabarbital, a weak acid, is most commonly administered orally in its sodium salt form.[12] 3–4 hours after oral administration butabarbital sodium reaches peak plama concentrations of 203 ug/mL for sedation, or 25 ug/mL to induce sleep, absorbed via the GI tract.[16]

Once absorbed, butabarbital's effects have a duration of 6–8 hours if orally administered, or 3–6 hours following intravaneous administration. General consensus has it with a half-life of approximately 100hr, however it has also been reported in one study to have a half life of 34-42 hr.[17]

The primary way the body terminates activity is by oxidation of radicals at C5, with other biotransformations contributing to a lesser extent.[18][19] Butabarbital is metabolized almost entirely by the liver, products including polar alcohols, ketones, phenols, or carboxylic acids, before it is renally excreted in the urine.[3]

Half-Life: ~100 hr Duration: 6-8 hr Onset: 45-60 min Enzymes induced: CYP1A2, CYP2C9/10, CYP3A4 Excretion: Urine

The mechanism of action by which barbiturates exert their effect is not yet completely understood, however they are believed to be involved in the enhancement of GABA inhibitory neurotransmitter activity in the CNS via GABA_A receptors.[14] Butabarbital, as a member of this drug class, acutely potentiates inhibitory GABAergic tone by binding with a specific site associated with a Cl⁻ ionophore at the GABA_A receptor.[20] Butabarbital's binding causes the channel to remain open longer and thus prolongs post-synaptic inhibition by GABA.[9] Less well characterized effects of barbiturates include direct inhibition of AMPA-type glutamate receptors, suppressing excitatory glutamatergic neurotransmission.[20]