Butabarbital

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Butabarbital
Butabarbital.svg
Clinical data
Trade names Butisol
AHFS/Drugs.com Professional Drug Facts
MedlinePlus a682417
License data
ATC code
  • none
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 100 hours [2]
Excretion Urine [3]
Identifiers
  • 5-butan-2-yl-5-ethyl-1,3-diazinane-2,4,6-trione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.004.308 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C10H16N2O3
Molar mass 212.249 g·mol−1
3D model (JSmol)
  • O=C1NC(=O)NC(=O)C1(C(C)CC)CC
  • InChI=1S/C10H16N2O3/c1-4-6(3)10(5-2)7(13)11-9(15)12-8(10)14/h6H,4-5H2,1-3H3,(H2,11,12,13,14,15) Yes check.svgY
  • Key:ZRIHAIZYIMGOAB-UHFFFAOYSA-N Yes check.svgY
   (verify)

Butabarbital (brand name Butisol) is a prescription barbiturate sleep aid and anxiety medication. Butabarbital has a particularly fast onset of effects and short duration of action compared to other barbiturates, which makes it useful for certain applications such as treating severe insomnia, relieving general anxiety and relieving anxiety before surgical procedures; however it is also relatively dangerous particularly when combined with alcohol, and so is now rarely used, although it is still prescribed in some Eastern European and South American countries. Its intermediate duration of action gives butabarbital an abuse potential slightly lower than secobarbital. Butabarbital can be hydrolyzed to valnoctamide. [4]

Contents

Stereoisomeres of butabarbital
(R)-Butabarbital.svg (S)-Butabarbital.svg
(R)-Stereoisomer(S)-Stereoisomer

Butabarbital is also sold in combination with belladonna alkaloids under the brand name Butibel. The belladonna is added for antispasmodic effect. This product contains a low dose of butabarbital combined with a standardised mix of belladonna alkaloids and is used as an antispasmodic taken to relieve cramping and spasms of the stomach and intestines. They are used also to decrease the amount of acid formed in the stomach. Another similar product is Donnatal, which contains belladonna alkaloids combined with phenobarbital.

History

Barbiturates were first discovered to have medical use in 1903, when a research at Bayer showed barbital to be an effective sedative for dogs. [5] It was not until the mid 20th century that the habit forming nature of barbiturates and behavioral side effects were first noted [6]

Benzodiazepines are more commonly administered today for their similar sedative and hypnotic properties, and reduced risk of physical dependence. Barbiturate drugs such as butabarbital sodium are used now for short-term and acute treatment under strict doctor supervision only [7]

Clinical uses

Barbiturates are non-selective depressants of the central nervous system, inducing drowsiness and mild sedative effects. Barbiturate hypnotics are used in the treatment of sleep and anxiety disorders for their calming and sedative properties, however are usually restricted to short term use due to risk of dependency. [8]

Butabarbital, most commonly known as Butisol commercially, is an approved Schedule III drug in the US and Canada used in the short-term treatment of anxiety disorders and as a pre-surgical sedative aid. Approved commercial forms are available in tablet or elixir forms. [9] Recently, butabarbital was approved for medical use in 2007 under the brand name Butisol Sodium. [8] Butisol sodium is manufactured by Meda Pharmaceuticals as a Schedule III controlled substance due to its high risk for abuse and dependence. [10]

Administration

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]

Clinical effects & elimination

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.

Overdose & abuse

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.

Side effects

Those taking butabarbital are asked to watch out for signs of severe allergic reaction, such as swelling or difficulty breathing. Less serious side effects include dizziness or drowsiness, excitation, headache, nausea, vomiting, or constipation. Psychiatric disturbances (hallucinations, agitation, confusion, depression, or memory problems), ataxia, difficulty breathing, or slow heartbeat could be signs of serious adverse effects and should be brought to the attention of a doctor immediately.

Adverse effects

[11]

1-10%

<1%

  • Apnea
  • Night terrors and sleep disturbances
  • Headache
  • Dizziness
  • Agitation or nervousness
  • Confusion
  • Nausea
  • Vomiting
  • Constipation
  • Hallucinations
  • Ataxia
  • Bradycardia
  • Hepatotoxicity
  • Hypoventilation
  • Fainting
  • Difficulty breathing or swallowing
  • Rash
  • Psychiatric disturbance

Contradictions

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]

Pharmacology

Butabarbital is a sedative hypnotic member of the barbiturate family. It is relatively fast acting, with a short duration, producing a range of effects from mild sedation to hypnosis as a function of dosage. [15] An overdose of butabarbital can result in deep coma or even death.

Absorption, distribution and excretion

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

Mechanism of action

The mechanism of action by which barbiturates exert their effect is not yet[ when? ] completely understood, however they are believed to be involved in the enhancement of GABA inhibitory neurotransmitter activity in the CNS via GABAA 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 GABAA 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]

Related Research Articles

<span class="mw-page-title-main">Hypnotic</span> Drug whose use induces sleep

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<span class="mw-page-title-main">Diazepam</span> Benzodiazepine sedative

Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken orally, as a suppository inserted into the rectum, intramuscularly, intravenously or used as a nasal spray. When injected intravenously, effects begin in one to five minutes and last up to an hour. Orally, effects begin after 15 to 60 minutes.

<span class="mw-page-title-main">Temazepam</span> Insomnia medication

Temazepam, sold under the brand name Restoril among others, is a medication of the benzodiazepine class which is generally used to treat severe or debilitating insomnia. It is taken by mouth. Temazepam is rapidly absorbed, and significant hypnotic effects begin in less than 30 minutes and can last for up to eight hours. Prescriptions for hypnotics such as temazepam have seen a dramatic decrease since 2010, while anxiolytics such as alprazolam, clonazepam, and lorazepam have increased or remained stable. Temazepam and similar hypnotics, such as triazolam (Halcion) are generally reserved for severe and debilitating insomnia. They have largely been replaced by z-drugs and atypical antidepressants as first line treatment for insomnia.

<span class="mw-page-title-main">Alprazolam</span> Benzodiazepine medication

Alprazolam, sold under the brand name Xanax, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly used in management of anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken orally.

<span class="mw-page-title-main">Lorazepam</span> Benzodiazepine medication

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting. It is also used during surgery to interfere with memory formation and to sedate those who are being mechanically ventilated. It is also used, along with other treatments, for acute coronary syndrome due to cocaine use. It can be given by mouth or as an injection into a muscle or vein. When given by injection, onset of effects is between one and thirty minutes and effects last for up to a day.

<span class="mw-page-title-main">Sedative</span> Drug that reduces excitement without inducing sleep

A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but the majority of them affect the neurotransmitter gamma-aminobutyric acid (GABA). In spite of the fact that each sedative acts in its own way, most produce relaxing effects by increasing GABA activity.

<span class="mw-page-title-main">Triazolam</span> Triazolobenzodiazepine class medication

Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.

<span class="mw-page-title-main">Hydroxyzine</span> Antihistamine drug

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<span class="mw-page-title-main">Nitrazepam</span> Benzodiazepine sedative

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<span class="mw-page-title-main">Flurazepam</span> Hypnotic medication

Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days. Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals, was one of the first benzodiazepine hypnotic medications to be marketed.

<span class="mw-page-title-main">Eszopiclone</span> Hypnotic medication

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<span class="mw-page-title-main">Meprobamate</span> Carbamate derivative used as an anxiolytic drug

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<span class="mw-page-title-main">Nonbenzodiazepine</span> Class of psychoactive drugs

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<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

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<span class="mw-page-title-main">Loprazolam</span> Benzodiazepine

Loprazolam (triazulenone) marketed under many brand names is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It is licensed and marketed for the short-term treatment of moderately-severe insomnia.

<span class="mw-page-title-main">Lormetazepam</span> Benzodiazepine medication

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<span class="mw-page-title-main">Chlordiazepoxide</span> Benzodiazepine class sedative and hypnotic medication

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<span class="mw-page-title-main">Delorazepam</span> Benzodiazepine medication

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<span class="mw-page-title-main">Benzoctamine</span> Chemical compound

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<span class="mw-page-title-main">Barbiturate</span> Class of depressant drugs derived from barbituric acid

Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential as well as overdose potential among other possible adverse effects. They have been used recreationally for their anti-anxiety and sedative effects, and are thus controlled in most countries due to the risks associated with such use.

References

  1. ↑ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. ↑ "Butisol". RxList. Archived from the original on 6 June 2011. Retrieved 11 March 2010.
  3. 1 2 Maynert EW, Losin L (November 1955). "The metabolism of butabarbital (butisol) in the dog". The Journal of Pharmacology and Experimental Therapeutics. 115 (3): 275–82. PMID   13272177.
  4. ↑ Freifelder M, Geiszler AO, Stone GR (1961). "Hydrolysis of 5,5-Disubstituted Barbituric Acids". The Journal of Organic Chemistry. 26 (1): 203–206. doi:10.1021/jo01060a048.
  5. ↑ "Barbiturates". Archived from the original on 7 November 2007. Retrieved 2007-10-31.
  6. ↑ Galanter M, Kleber HD (1 July 2008). The American Psychiatric Publishing Textbook of Substance Abuse Treatment (4th ed.). United States of America: American Psychiatric Publishing Inc. p. 217. ISBN   978-1-58562-276-4.
  7. ↑ "Barbiturates vs. Benzodiazepines". Pat Moore Foundation. 19 February 2014. Archived from the original on 26 January 2016.
  8. 1 2 "FDA Approved Labeling text for NDA 793/S- 025 (Butisol Sodium oral soln)" (PDF). U.S. Food and Drug Administration. 18 September 2007.
  9. 1 2 3 "Butabarbital". DrugBank.
  10. ↑ "Butisol Sodium (Butabarbital Sodium Tablets, USP and Butabarbital Sodium Oral Solution, USP) Tablets & Oral Solution" (PDF). U.S. Food and Drug Administration. December 2018.
  11. 1 2 "Butabarbital (Rx) - Butisol". MedScape. WebMD, LLC. 1994–2014.
  12. 1 2 3 4 "Butisol sodium- butabarbital sodium tablet". DailyMed. 12 August 2015. Retrieved 28 January 2020.
  13. ↑ "Butabarbital-sodium". Drugs.com.
  14. 1 2 3 American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 2579
  15. ↑ "Butisol sodium". RxList.
  16. ↑ "Butabarbital (Compound)". PubChem. U.S. National Library of Medicine.
  17. ↑ "Butasol". RxList Inc.
  18. ↑ Gilman AG, Rall TW, Nies AS, Taylor P, eds. (1991). "The Mechanisms of Drug Action". Goodman & Gilman's The Pharmacological Basis of Therapeutics (8th ed.). New York: Pergamon Press. p.  36. ISBN   0-08-040296-8.
  19. ↑ Goodman LS, Gilman AS, eds. (1975). The Pharmacological Basis of Therapeutics (5th ed.). New York: Macmillan. p. 116. ISBN   0023447818.
  20. 1 2 "Butabarbital". PubChem. U.S. National Library of Medicine.
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