Pentobarbital

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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
Pharmacokinetic data
Bioavailability70–90% (oral); 90% (rectal)
Protein binding20–45%
MetabolismLiver
Elimination half-life15–48 hours
ExcretionKidney
Identifiers
  • 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 Edit this at Wikidata
Chemical and physical data
FormulaC11H18N2O3
Molar mass226.27 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) checkY
  • Key:WEXRUCMBJFQVBZ-UHFFFAOYSA-N checkY
  (verify)

Pentobarbital (INN, AAN, BAN, USAN) or pentobarbitone (former AAN and BAN) is a short-acting barbiturate. Pentobarbital can occur as both a free acid and as salts of elements such as sodium and calcium. The free acid is only slightly soluble in water and ethanol.[1][2]

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).[3] 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.[4]

In high doses, pentobarbital causes death by respiratory arrest. In the United States, the drug has been used for executions of convicted criminals. Lundbeck (one of many manufacturers) does not permit its sale to prisons or corrections departments to carry out the death penalty.[5]

Uses

Medical

Typical applications for pentobarbital are sedative, hypnotic for short term, preanesthetic and control of convulsions in emergencies.[6]

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

Pentobarbital also has an application in reducing intracranial pressure in Reye's syndrome, traumatic brain injury and induction of 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 induce 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, the standard protocol for physician-assisted suicide is to provide 9 grams of pentobarbital sodium along with sugar syrup in a 20% ethanol solution for self-administration by the patient.[10]

The oral dosage of pentobarbital indicated for physician-assisted death in the United States states of Oregon, Washington, Vermont, and California (as of January, 2016) is typically 10 g in liquid form.[11][12] This is considerably higher than the dose for the management of status epilepticus.[13]

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.[14] 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.[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 relaxant previously used as one component in a three-drug cocktail.[17]

In October 2013, Missouri changed its protocols to allow for a compounded pentobarbital to be used in a lethal dose for executions.[18] On November 20, 2013, Joseph Paul Franklin was executed by the state of Missouri.[19] He was the first inmate executed in three years in the state and the first to die by a single dose of pentobarbital.[20]

Metabolism

Pentobarbital undergoes first-pass metabolism in the liver and possibly the intestines.[21]

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 (not 1-bromo-3-methylbutane) to give pentobarbital.[22][23][24]

References

  1. ^ "Pentobarbital Compound summary (CID4737)". Pubchem. NCBI.
  2. ^ "FR1972_08_25_17226" (PDF). Food and Drug Administration. {{cite journal}}: Cite journal requires |journal= (help)
  3. ^ 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.
  4. ^ Jolly, David (1 Jul 2011). "Danish Company Blocks Sale of Drug for U.S. Executions". The New York Times. Retrieved 20 Nov 2013.
  5. ^ "Ohio says it will switch to new drugs for executions". Reuters. Oct 28, 2013.
  6. ^ "NEMBUTAL SODIUM (pentobarbital sodium) injection, solution". DailyMed, National Institutes of Health.
  7. ^ "International". Drugs.com.
  8. ^ a b "Pentobarbital". Monograph. AHFS / Drugs.com.
  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.
  10. ^ "Euthanica". Euthanesia Dossier (in Dutch). NRC Webpagina's.
  11. ^ 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.
  12. ^ Philip Nitschke; Fiona Stewart (2006). The Peaceful Pill Handbook. Exit International US Ltd. p. 137. ISBN 0978878809.
  13. ^ Lexi-Comp Inc. (2010) Lexi-Comp Drug Information Handbook 19th North American Ed. Hudson, OH: Lexi-Comp Inc. ISBN 978-1-59195-278-7.[page needed]
  14. ^ "States urge feds to help import lethal injection drugs". CNN. May 21, 2012.
  15. ^ "The Hidden Hand Squeezing Texas' Supply of Execution Drugs". Time. 7 August 2013.
  16. ^ "Texas executes Yokamon Hearn with pentobarbitol". BBC News. 18 July 2012.
  17. ^ "Texas executes Yokamon Hearn with pentobarbitol". Retrieved 9 December 2017. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  18. ^ "Lethal injection: Secretive US states resort to untested drugs - BBC News". BBC News. Retrieved 2016-03-17.
  19. ^ https://news.yahoo.com/missouri-executes-serial-killer-franklin-122636393.html[full citation needed]
  20. ^ http://www.christianpost.com/news/joseph-paul-franklin-executed-first-mo-inmate-killed-using-pentobarbital-109150/[full citation needed]
  21. ^ 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. PMID 6777235.
  22. ^ Volwiler, E. H.; Tabern, D. L. (1930). "5,5-SUBSTITUTED BARBITURIC ACIDS". Journal of the American Chemical Society. 52 (4): 1676–1679. doi:10.1021/ja01367a061.
  23. ^ German imperial patent, D.R.P. 293163 (1916), Bayer
  24. ^ 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 
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