Pentobarbital

Pentobarbital, also known as pentobarbitone, is a short-acting barbiturate. 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. Abbott Pharmaceuticals' brand of pentobarbital, Nembutal, which was available in 50 and 100 mg yellow capsules, was discontinued in 1999. Prescribed for insomnia, it has been largely replaced by the benzodiazepine family of drugs. Nembutal was widely abused and known on the streets as "yellow jackets" due to their yellow capsule. Pentobarbital in pill form is no longer available. The death of Marilyn Monroe in 1962 was ruled as probable suicide due to an overdose of Nembutal.[1] Kenneth Halliwell's death is also attributed to an overdose of Nembutal.

Not to be confused with phenobarbital or sodium pentothal.
Pentobarbital
Clinical data
Trade namesNembutal
AHFS/Drugs.comMonograph
MedlinePlusa682416
License data
Pregnancy
category
  • AU: C
  • US: D (Evidence of risk)
    Routes of
    administration    		By mouth, IV, IM, rectal; also intraperitoneal & intracardiac (for animal euthanasia)
    ATC code
    Legal status
    Legal status
    • AU: S8 (Controlled)
    • 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
    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)
      (verify)

    Uses

    Medical

    Typical applications for pentobarbital are sedative, hypnotic for short term, preanesthetic, insomnia, and control of convulsions in emergencies. 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 streets as "yellow jackets". They were available in 50 and 100 mg. yellow capsules. Pentobarbital in pill form is no longer manufactured.[2]

    It is also used as a veterinary anesthetic agent.[3]

    Pentobarbital also has an application in reducing intracranial pressure in Reye's syndrome, traumatic brain injury and induction of coma in cerebral ischemia patients.[4] Pentobarbital-induced coma has been advocated in patients with acute liver failure refractory to mannitol.[5]

    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.

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

    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.[6]

    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.[7][8] This is considerably higher than the dose for the management of status epilepticus.[9]

    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.[10] 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.[11]

    Texas began using pentobarbital for executing death-row inmates by lethal injection on July 18, 2012.[12] 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.[12]

    In October 2013, Missouri changed its protocols to allow for a compounded pentobarbital to be used in a lethal dose for executions[13] and it was first used in November 2013.[14][15]

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

    Metabolism

    Pentobarbital undergoes first-pass metabolism in the liver and possibly the intestines.[17]

    Drug interactions

    Administration of ethanol, benzodiazepines, opioids, antihistamines, other sedative-hypnotics, and other central nervous system depressants will cause possible additive effects.[4]

    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.[18][19][20]

    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).[21] 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.[22]

    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.[23][24]

    References
    1. "Ohio says it will switch to new drugs for executions". Reuters. Oct 28, 2013.
    2. "NEMBUTAL SODIUM (pentobarbital sodium) injection, solution". DailyMed, National Institutes of Health.
    3. "International". Drugs.com.
    4. "Pentobarbital". Monograph. AHFS / Drugs.com.
    5. 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.
    6. "Euthanica". Euthanesia Dossier (in Dutch). NRC Webpagina's.
    7. 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.
    8. Philip Nitschke; Fiona Stewart (2006). The Peaceful Pill Handbook. Exit International US Ltd. p. 137. ISBN 0978878809.
    9. Lexi-Comp Inc. (2010) Lexi-Comp Drug Information Handbook 19th North American Ed. Hudson, OH: Lexi-Comp Inc. ISBN 978-1-59195-278-7.
    10. "States urge feds to help import lethal injection drugs". CNN. May 21, 2012.
    11. "The Hidden Hand Squeezing Texas' Supply of Execution Drugs". Time. 7 August 2013.
    12. "Texas executes Yokamon Hearn with pentobarbitol". BBC News. 18 July 2012. Retrieved 9 December 2017.
    13. "Lethal injection: Secretive US states resort to untested drugs - BBC News". BBC News. Retrieved 2016-03-17.
    14. "Missouri executes serial killer Franklin". November 20, 2013.
    15. "Joseph Paul Franklin Executed; First MO Inmate Killed Using Pentobarbital". November 20, 2013.
    16. AG Barr orders reinstatement of the federal death penalty
    17. 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.
    18. 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.
    19. German imperial patent, D.R.P. 293163 (1916), Bayer
    20. 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
    21. 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.
    22. Jolly, David (1 Jul 2011). "Danish Company Blocks Sale of Drug for U.S. Executions". The New York Times. Retrieved 20 Nov 2013.
    23. "Pentobarbital Compound summary (CID4737)". Pubchem. NCBI.
    24. "FR1972_08_25_17226" (PDF). Food and Drug Administration. Cite journal requires |journal= (help)
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