Pentobarbital

Pentobarbital (previously known as pentobarbitone in Britain and Australia) is a short-acting barbiturate typically used as a sedative, a preanesthetic, and to control convulsions in emergencies.[1] It can also be used for short-term treatment of insomnia but has been largely replaced by the benzodiazepine family of drugs.

Not to be confused with phenobarbital or sodium pentothal.

Pentobarbital
Clinical data
Trade namesNembutal
AHFS/Drugs.comMonograph
MedlinePlusa682416
License data
Pregnancy
category
  • AU: C
Routes of
administration		By mouth, IV, IM, rectal; also intraperitoneal & intracardiac (for animal euthanasia)
ATC code
Legal status
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)
Pharmacokinetic data
Bioavailability70–90% (oral); 90% (rectal)
Protein binding20–45%
MetabolismLiver
Elimination half-life15–48 hours
ExcretionKidney
Identifiers
IUPAC name
  • 5-Ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.895
Chemical and physical data
FormulaC11H18N2O3
Molar mass226.276 g·mol−1
3D model (JSmol)
  • O=C1NC(=O)NC(=O)C1(C(C)CCC)CC
  • 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) Y
  • Key:WEXRUCMBJFQVBZ-UHFFFAOYSA-N Y
  (verify)

In high doses, pentobarbital causes death by respiratory arrest. It is used for veterinary euthanasia and is used by some U.S. states and the U.S. federal government for executions of convicted criminals.[2] In some countries and states, it is also used for physician-assisted suicide.[3][4]

Pentobarbital was widely abused and sometimes known as "yellow jackets" due to the yellow capsule of the Nembutal brand. Pentobarbital in oral (pill) form is no longer commercially available.[2]

Uses

Medical

Typical applications for pentobarbital are sedative, short term hypnotic, preanesthetic, insomnia treatment, and control of convulsions in emergencies.[1] 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".[5] They were available as 30, 50, and 100 mg capsules of yellow, white-orange, and yellow colors, respectively.[6]

It is also used as a veterinary anesthetic agent.[7]

Pentobarbital can reduce intracranial pressure in Reye's syndrome, treat traumatic brain injury and induce coma in cerebral ischemia patients.[8] Pentobarbital-induced coma has been advocated in patients with acute liver failure refractory to mannitol.[9]

Euthanasia

Pentobarbital can cause death when used in high doses. It is used for euthanasia for humans as well as animals. It is taken alone, or in combination with complementary agents such as phenytoin, in commercial animal euthanasia injectable solutions.[3][4]

Pentobarbital Sodium (CAS No. 57-33-0)

In the Netherlands, it is part of the standard protocol for physician-assisted suicide for self-administration by the patient.[10]

It is taken by mouth for physician-assisted death in the United States states of Oregon, Washington, Vermont, and California (as of January 2016).[11][12]

The oral dosage of pentobarbital indicated for physician-assisted suicide in Oregon is typically 10 g of liquid.[11][12]

In Switzerland, sodium pentobarbital is administered to the patient intravenously. Once administered, sleep is induced within 30 seconds, and the heart stops beating within 3 minutes.[13]

Execution

Pentobarbital has been used or considered as a substitute for other drugs previously used for capital punishment in the United States when those drugs are unavailable.[14] Such use 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 state authorities, that practice or participate in executions of humans.[15]

Texas began using pentobarbital for executing death-row inmates by lethal injection on July 18, 2012.[16] 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.[16]

In October 2013, Missouri changed its protocol to allow for compounded pentobarbital to be used in a lethal dose for executions.[17] It was first used in November 2013.[18][19]

According to a December 2019 ProPublica article, by 2017 the Bureau of Prisons (BOP), in discussion with then Attorney General Jeff Sessions, had begun to search for suppliers of pentobarbital to be used in lethal injections. The BOP was aware that the use of pentobarbital as their "new drug choice" would be challenged in the courts because some lawyers had said that "pentobarbital would flood prisoners’ lungs with froth and foam, inflicting pain and terror akin to a death by drowning." BOP claimed that these concerns were unjustified and that their two expert witnesses asserted that the use of pentobarbital was "humane".[20] 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 was pentobarbital.[21]

Metabolism

Pentobarbital undergoes first-pass metabolism in the liver and possibly the intestines.[22]

Drug interactions

Administration of ethanol, benzodiazepines, opioids, antihistamines, other sedative-hypnotics, and other central nervous system depressants will cause possible additive effects.[8]

Chemistry

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.[23][24][25]

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).[26] 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, known on the streets as "yellow jackets", was widely abused. It was available in 50 and 100 mg strength yellow capsules.[27]

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.[28][29]

See also
  • Animal euthanasia
  • List of veterinary drugs

References
  1. "Nembutal sodium- pentobarbital sodium injection". DailyMed. 31 December 2016. Retrieved 29 January 2020.
  2. "Ohio says it will switch to new drugs for executions". Reuters. 28 October 2013.
  3. "Euthanasia drugs: What is needed from medications for assisted deaths?". abc.net.au. Australian Broadcasting Corporation. 20 October 2017. Retrieved 22 September 2021. Both secobarbital capsules and pentobarbital (usually known as the brand name, Nembutal) liquid — (not to be mistaken for epilepsy medication phenobarbital) have been used either alone or in combination for physician-assisted suicide or euthanasia. They are also used in injectable forms for animal euthanasia.
  4. "Euthanasia referendum: What drugs are used in assisted dying, and how do they work?". Stuff. 13 August 2020. Retrieved 22 September 2021. In Australia, most people will ingest the lethal dose of pentobarbital as a drink – a white powder mixed with about 30 millilitres of a liquid suspension. [...] However, in cases where the person is too ill to ingest the medication themselves, a doctor or nurse practitioner could administer the dose, under the proposed Act.
  5. High Times Encyclopedia of Recreational Drugs. Aldrich, Michael R., Ashley, Richard, Horowitz, Michael. New York: Stonehill. 1978. p. 243. ISBN 0-88373-082-0. OCLC 4557439.{{cite book}}: CS1 maint: others (link)
  6. Physicians' Desk Reference (33rd ed.). Oradell, New Jersey: Medical Economics Co. 1979. p. 403. ISBN 0-87489-999-0. OCLC 4636066.
  7. "Pentobarbital". Drugs.com.
  8. "Pentobarbital" (Monograph). Drugs.com. AHFS.
  9. 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.
  10. "Euthanica". Euthanesia Dossier (in Dutch). NRC Webpagina's.
  11. Fass, Jennifer; Fass, Andrea (2011). "Physician-assisted Suicide: Ongoing Challenges for Pharmacists". Am J Health Syst Pharm. 68 (9): 846–849. doi:10.2146/ajhp100333. PMID 21515870.
  12. Nitschke, Philip; Stewart, Fiona (2006). The Peaceful Pill Handbook. Exit International US Ltd. p. 137. ISBN 0978878809 – via Google Books.
  13. On February 9, the Dying With Dignity Canada team was joined by Dr. Erika Preisig to learn about assisted dying in Switzerland, see 39:00-41:19 min
  14. "States urge feds to help import lethal injection drugs". CNN. 21 May 2012.
  15. "The Hidden Hand Squeezing Texas' Supply of Execution Drugs". Time. 7 August 2013.
  16. "Texas executes Yokamon Hearn with pentobarbitol". bbc.co.uk. BBC News. 18 July 2012. Retrieved 9 December 2017.
  17. "Lethal injection: Secretive US states resort to untested drugs". bbc.co.uk. BBC News. 15 November 2013. Retrieved 17 March 2016.
  18. "Missouri executes serial killer Franklin". Yahoo News. 20 November 2013.
  19. Martin, Sami K. (20 November 2013). "Joseph Paul Franklin Executed; First MO Inmate Killed Using Pentobarbital". Christian Post.
  20. Arnsdorf, Isaac (23 December 2020). "Inside Trump and Barr's Last-Minute Killing Spree". ProPublica. Retrieved 11 January 2021.
  21. Williams, Pete; Arkin, Daniel (25 July 2019). "AG Barr orders reinstatement of the federal death penalty". NBC News.
  22. 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.
  23. 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.
  24. German imperial patent, D.R.P. 293163 (1916), Bayer
  25. 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
  26. 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.
  27. Jolly, David (1 July 2011). "Danish Company Blocks Sale of Drug for U.S. Executions". The New York Times. Retrieved 20 November 2013.
  28. "Pentobarbital Compound summary (CID4737)". Pubchem. NCBI.
  29. "FR1972_08_25_17226" (PDF). Food and Drug Administration. {{cite journal}}: Cite journal requires |journal= (help)
  • "Pentobarbital". Drug Information Portal. U.S. National Library of Medicine.
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