Pentobarbital

Not to be confused with phenobarbital or sodium pentothal.

Pentobarbital
Names
Trade namesNembutal, others
Other namesPentobarbitone
IUPAC name
  • 5-Ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
Clinical data
Drug classBarbiturate[1]
Main usesStatus epilepticus, acute agitation, short term management of trouble sleeping, surgery[1]
Side effectsSleepiness, vomiting, headache, delirium, abuse, respiratory arrest,anaphylaxis[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
    Routes of
    use    		By mouth, IV, IM, rectal; also intraperitoneal & intracardiac (for animal euthanasia)
    Onset of action< 1 min (IV), < 25 min (IM)[1]
    Duration of action15 min (IV)[1]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa682416
    Legal
    License data
    Legal status
    • AU: S8 (Controlled drug)
    • CA: Schedule IV
    • DE: Anlage III (Special prescription form required)
    • UK: Class B
    • US: Schedule II
    • UN: Psychotropic Schedule III
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    Bioavailability70–90% (by mouth); 90% (rectal)
    Protein binding20–45%
    MetabolismLiver
    Elimination half-life15–48 hours
    ExcretionKidney
    Chemical and physical data
    FormulaC11H18N2O3
    Molar mass226.276 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C1NC(=O)NC(=O)C1(C(C)CCC)CC
    InChI
    • InChI=1S/C11H18N2O3/c1-4-6-7(3)11(5-2)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16) checkY
    • Key:WEXRUCMBJFQVBZ-UHFFFAOYSA-N checkY

    Pentobarbital is a medication that has been used for status epilepticus, acute agitation, short term management of trouble sleeping, surgery, and to put someone in a coma.[1] It is used by injection into a muscle or vein.[1] The by mouth formulation has been discontinued in the United States.[2] Onset is within a minute when given into a vein and within 25 minutes when into a muscle.[1] When given into a vein effects last about 15 minutes.[1]

    Common side effects include sleepiness, vomiting, and headache.[1] Severe side effects include delirium, abuse, respiratory arrest, and anaphylaxis.[1] Use is not recommended in pregnancy.[1] It is in the barbiturate family of medications.[1] It works by increasing the activity of GABA in the brain.[1]

    Pentobarbital came into medical use in the United States in 1930 by John Lundy.[3] They were widely misused in the 1970s and known as "yellow jackets" due to their color.[4] It is used for veterinary euthanasia and some US states for executions of criminals.[5][6] The death of Marilyn Monroe in 1962 was due to an overdose of pentobarbital and chloral hydrate.[7]

    Uses

    Medical

    Typical applications for pentobarbital are sedative, short term hypnotic, preanesthetic, insomnia, and control of convulsions in emergencies.[8] Abbott Pharmaceutical discontinued manufacture of their Nembutal brand of Pentobarbital capsules in 1999, largely replaced by the benzodiazepine family of drugs. Pentobarbital was also widely abused, known on the street as "yellow jackets". They were available in 50 and 100 mg yellow capsules.

    It is also used as a veterinary anesthetic agent.[9]

    Pentobarbital also has an application in reducing intracranial pressure in Reye's syndrome, traumatic brain injury and induction of coma in cerebral ischemia patients.[10] Pentobarbital-induced coma has been advocated in patients with acute liver failure refractory to mannitol.[11]

    Euthanasia

    Pentobarbital can cause death when used in high doses. It is used for euthanasia for humans as well as animals. It is also used by itself, or in combination with complementary agents such as phenytoin, in commercial animal euthanasia injectable solutions.

    In the Netherlands, it is part of the standard protocol for physician-assisted suicide for self-administration by the patient.[12]

    It is also used by mouth for physician-assisted death in the United States states of Oregon, Washington, Vermont, and California (as of January, 2016).[13][14] This is considerably higher than the dose for the management of status epilepticus.[15]

    Execution

    Pentobarbital has been used or considered as a substitute for other drugs traditionally used for capital punishment in the United States when they are in short supply.[16] Such use however is illegal under Danish law, and when this was discovered, after public outcry in Danish media, Lundbeck, the owner of the drug, stopped selling it to US states that impose the death penalty. US distributors of the drug are forbidden by the owner to sell it to any customers, such as several state authorities, that practice or participate in executions of humans.[17]

    Texas began using pentobarbital for executing death-row inmates by lethal injection on July 18, 2012.[18] The use of pentobarbital has been considered by several states, including Ohio, Arizona, Idaho, and Washington; those states made the decision to switch following shortages of pancuronium bromide, a muscle paralytic previously used as one component in a three-drug cocktail.[18]

    In October 2013, Missouri changed its protocols to allow for a compounded pentobarbital to be used in a lethal dose for executions[19] and it was first used in November 2013.[20][21]

    On July 25, 2019, US Attorney General William Barr directed the federal government to resume capital punishment after 16 years. The drug of choice for these executions is pentobarbital.[22]

    Interactions

    Administration of ethanol, benzodiazepines, opioids, antihistamines, other sedative-hypnotics, and other central nervous system depressants will cause possible additive effects.[10]

    Metabolism

    Pentobarbital undergoes first-pass metabolism in the liver and possibly the intestines.[23]

    Chemistry

    Pentobarbital

    Pentobarbital is synthesized by methods analogous to that of amobarbital, the only difference being that the alkylation of α-ethylmalonic ester is carried out with 2-bromopentane in place of 1-bromo-3-methylbutane to give pentobarbital.[24][25][26]

    Society and culture

    Names

    Pentobarbital is the INN, AAN, BAN, and USAN while pentobarbitone is a former AAN and BAN.

    One brand name for this drug is Nembutal, coined by John S. Lundy, who started using it in 1930, from the structural formula of the sodium salt—Na (sodium) + ethyl + methyl + butyl + al (common suffix for barbiturates).[27] Nembutal is trademarked and manufactured by the Danish pharmaceutical company Lundbeck (now produced by Akorn Pharmaceuticals) and is the only injectable form of pentobarbital approved for sale in the United States. Abbott discontinued their Nembutal brand of Pentobarbital capsules in 1999, largely replaced by the Benzodiazepine family of drugs. Abbott's Nembutal brand of Pentobarbital capsules were widely abused and were known on the streets as "yellow jackets". They were available in 50 and 100 Mg.strength yellow capsules.[28]

    Pentobarbital can occur as a free acid, but is usually formulated as the sodium salt, pentobarbital sodium. The free acid is only slightly soluble in water and in ethanol.[29][30]

    Notable overdoses

    Capsules that were take by mouth

    The death of Marilyn Monroe in 1962 was ruled as probable suicide due to an overdose of pentobarbital.[31] Kenneth Halliwell's death is also attributed to an overdose of pentobarbital.

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Pentobarbital Monograph for Professionals". Drugs.com. Archived from the original on 30 June 2018. Retrieved 11 December 2020.
    2. ↑ Administration, Food and Drug. Approved Drug Products with Therapeutic Equivalence Evaluations - FDA Orange Book 32nd Edition (2012): FDA Orange Book 32nd Edition (2012). DrugPatentWatch.com. p. PR736. ISBN 978-1-934899-82-3. Archived from the original on 28 August 2021. Retrieved 11 December 2020.
    3. ↑ Lamberth, Clemens; Dinges, Jürgen (2012). Bioactive Heterocyclic Compound Classes: Pharmaceuticals. John Wiley & Sons. p. PA30. ISBN 978-3-527-66447-4. Archived from the original on 28 August 2021. Retrieved 11 December 2020.
    4. ↑ Caroline, Nancy L.; Elling, Bob (2007). Nancy Caroline's Emergency Care in the Streets, Volume 2. Jones & Bartlett Learning. p. SA33-PA17. ISBN 978-0-7637-4239-3. Archived from the original on 28 August 2021. Retrieved 11 December 2020.
    5. ↑ "Why the Justice Department's Plan to Use a Single Drug for Lethal Injections Is Controversial". Time. 2019. Archived from the original on 11 December 2020. Retrieved 11 December 2020.
    6. ↑ "What Happens When You Put Your Pet to Sleep?". WebMD. Archived from the original on 16 November 2020. Retrieved 11 December 2020.
    7. ↑ "New Chapter in the Mystery of Marilyn: Her Own Words?". Los Angeles Times. 5 August 2005. Archived from the original on 1 August 2020. Retrieved 11 December 2020.
    8. ↑ "Nembutal sodium- pentobarbital sodium injection". DailyMed. 31 December 2016. Archived from the original on 11 January 2017. Retrieved 29 January 2020.
    9. ↑ "International". Drugs.com. Archived from the original on 30 June 2018. Retrieved 10 May 2018.
    10. 1 2 "Pentobarbital". Monograph. AHFS / Drugs.com. Archived from the original on 30 June 2018. Retrieved 10 May 2018.
    11. ↑ Stravitz RT, Kramer AH, Davern T, Shaikh AO, Caldwell SH, Mehta RL, Blei AT, Fontana RJ, McGuire BM, Rossaro L, Smith AD, Lee WM (2007). "Intensive care of patients with acute liver failure: Recommendations of the U.S. Acute Liver Failure Study Group". Critical Care Medicine. 35 (11): 2498–2508. doi:10.1097/01.CCM.0000287592.94554.5F. PMID 17901832. S2CID 11924124.
    12. ↑ "Euthanica". Euthanesia Dossier (in Nederlands). NRC Webpagina's. Archived from the original on 27 March 2017. Retrieved 25 June 2012.
    13. ↑ Jennifer Fass; Andrea Fass (2011). "Physician-assisted Suicide: Ongoing Challenges for Pharmacists". Am J Health Syst Pharm. 68 (9): 846–849. doi:10.2146/ajhp100333. PMID 21515870. Archived from the original on 2 August 2019. Retrieved 3 May 2013.
    14. ↑ Philip Nitschke; Fiona Stewart (2006). The Peaceful Pill Handbook. Exit International US Ltd. p. 137. ISBN 0978878809. Archived from the original on 22 February 2018. Retrieved 24 September 2016.
    15. ↑ Lexi-Comp Inc. (2010) Lexi-Comp Drug Information Handbook 19th North American Ed. Hudson, OH: Lexi-Comp Inc. ISBN 978-1-59195-278-7.
    16. ↑ "States urge feds to help import lethal injection drugs". CNN. 21 May 2012. Archived from the original on 28 August 2017. Retrieved 3 May 2013.
    17. ↑ "The Hidden Hand Squeezing Texas' Supply of Execution Drugs". Time. 7 August 2013. Archived from the original on 29 March 2017. Retrieved 8 August 2013.
    18. 1 2 "Texas executes Yokamon Hearn with pentobarbitol". BBC News. 18 July 2012. Archived from the original on 5 January 2018. Retrieved 9 December 2017.
    19. ↑ "Lethal injection: Secretive US states resort to untested drugs - BBC News". BBC News. Archived from the original on 12 April 2019. Retrieved 17 March 2016.
    20. ↑ "Missouri executes serial killer Franklin". 20 November 2013. Archived from the original on 24 March 2016. Retrieved 9 January 2017.
    21. ↑ "Joseph Paul Franklin Executed; First MO Inmate Killed Using Pentobarbital". 20 November 2013. Archived from the original on 10 June 2015. Retrieved 20 November 2013.
    22. ↑ "AG Barr orders reinstatement of the federal death penalty". Archived from the original on 9 October 2019. Retrieved 25 July 2019.
    23. ↑ Knodell RG, Spector MH, Brooks DA, Keller FX, Kyner WT (1980). "Alterations in pentobarbital pharmacokinetics in response to parenteral and enteral alimentation in the rat". Gastroenterology. 79 (6): 1211–1216. doi:10.1016/0016-5085(80)90915-4. PMID 6777235.
    24. ↑ Volwiler, E. H.; Tabern, D. L. (1930). "5,5-Substituted Barbituric Acids1". Journal of the American Chemical Society. 52 (4): 1676–1679. doi:10.1021/ja01367a061.
    25. ↑ German imperial patent, D.R.P. 293163 (1916), Bayer
    26. ↑ GB patent 650354, Wilde, B. E. & Balaban, I. E., "Improvements in the manufacture of substituted barbituric and thiobarbituric acids", issued 1951-02-21, assigned to Geigy 
    27. ↑ Fosburgh LC (1997). "From this point in time: Some memories of my part in the history of anesthesia--John S. Lundy, MD". AANA Journal. 65 (4): 323–328. PMID 9281913.
    28. ↑ Jolly, David (1 July 2011). "Danish Company Blocks Sale of Drug for U.S. Executions". The New York Times. Archived from the original on 21 December 2013. Retrieved 20 November 2013.
    29. ↑ "Pentobarbital Compound summary (CID4737)". Pubchem. NCBI. Archived from the original on 14 February 2014. Retrieved 10 May 2018.
    30. ↑ "FR1972_08_25_17226" (PDF). Food and Drug Administration. Archived (PDF) from the original on 8 February 2017. Retrieved 16 December 2019. {{cite journal}}: Cite journal requires |journal= (help)
    31. ↑ "Ohio says it will switch to new drugs for executions". Reuters. 28 October 2013. Archived from the original on 10 January 2015. Retrieved 1 July 2017.
    Identifiers:
    • "Pentobarbital". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 30 January 2020. Retrieved 30 January 2020.
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