Pentobarbital

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Pentobarbital
Pentobarbital2DCSD.svg
Pentobarbital3DanJ.gif
Systematic (IUPAC) name
5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
Clinical data
Trade namesNembutal
AHFS/Drugs.commonograph
MedlinePlusa682416
Pregnancy cat.
Legal status
RoutesOral, Intravenous, Intramuscular, Rectal; also Intraperitoneal & Intracardiac (for animal euthanasia)
Pharmacokinetic data
Bioavailability70-90% oral; 90% rectal
Protein binding20-45%
MetabolismHepatic
Half-life15-48 hours
ExcretionRenal
Identifiers
CAS number76-74-4 YesY
ATC codeN05CA01 QN51AA01
PubChemCID 4737
DrugBankDB00312
ChemSpider4575 YesY
UNIII4744080IR YesY
KEGGD00499 YesY
ChEBICHEBI:7983 YesY
ChEMBLCHEMBL448 YesY
Chemical data
FormulaC11H18N2O3 
Mol. mass226.27
 YesY (what is this?)  (verify)
 
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Not to be confused with Phenobarbital.
Pentobarbital
Pentobarbital2DCSD.svg
Pentobarbital3DanJ.gif
Systematic (IUPAC) name
5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
Clinical data
Trade namesNembutal
AHFS/Drugs.commonograph
MedlinePlusa682416
Pregnancy cat.
Legal status
RoutesOral, Intravenous, Intramuscular, Rectal; also Intraperitoneal & Intracardiac (for animal euthanasia)
Pharmacokinetic data
Bioavailability70-90% oral; 90% rectal
Protein binding20-45%
MetabolismHepatic
Half-life15-48 hours
ExcretionRenal
Identifiers
CAS number76-74-4 YesY
ATC codeN05CA01 QN51AA01
PubChemCID 4737
DrugBankDB00312
ChemSpider4575 YesY
UNIII4744080IR YesY
KEGGD00499 YesY
ChEBICHEBI:7983 YesY
ChEMBLCHEMBL448 YesY
Chemical data
FormulaC11H18N2O3 
Mol. mass226.27
 YesY (what is this?)  (verify)

Pentobarbital (US English) or Pentobarbitone (UK English) is a short-acting barbiturate. Pentobarbital can occur as both a free acid and as a 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, 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 humans. Lundbeck does not permit its sale to prisons or corrections departments to carry out the death penalty.[5]

Uses[edit]

Medical[edit]

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[edit]

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 intravenously induced thiopental anesthesia, followed by bromide of alcuronium- or pancuronium-induced respiratory arrest. A concentrated oral solution of 100 ml containing 9 grams of pentobarbital sodium along with sugar syrup in a 20% ethanol solution is a standard solution used for self-administration by patient.[10]

The oral dosage of pentobarbital indicated for physician-assisted suicide in Oregon, US is typically 10 g in liquid form.[11][12] This is considerably higher than the dose for the management of status epilepticus.[13]

Capital punishment[edit]

Pentobarbital has been used or considered as a substitute for other drugs traditionally used in the United States for execution when they are in short supply.[14] Such use however is illegal under Danish law, and when this was discovered, the owner of the drug, Lundbeck, stopped selling it to states that practice death penalty after public outcry in Danish media. 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 the pancuronium bromide, a muscle relaxant previously used as one component in a three-drug cocktail.[17][unreliable source?][dubious ]

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[edit]

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

Pentobarbital DOJ.jpg

Drug interactions[edit]

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

Chemistry[edit]

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[edit]

  1. ^ "Pentobarbital Compound summary (CID4737)". Pubchem. NCBI. 
  2. ^ "FR1972_08_25_17226". Food and Drug Administration. 
  3. ^ Fosburgh, L. C. (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.  edit
  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, R. T.; Kramer, A. H.; Davern, T.; Shaikh, A. O. S.; Caldwell, S. H.; Mehta, R. L.; Blei, A. T.; Fontana, R. J.; McGuire, B. M.; Rossaro, L.; Smith, A. D.; Lee, W. M.; Acute Liver Failure Study Group (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.  edit
  10. ^ "Euthanica". Euthanesia Dossier (in Dutch). NRC Webpagina's. 
  11. ^ Jennifer Fass and Andrea Fass (2011). "Physician-assisted Suicide: Ongoing Challenges for Pharmacists". Am J Health Syst Pharm 68 (9): 846–849. doi:10.2146/ajhp100333. 
  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.
  14. ^ "States urge feds to help import lethal injection drugs". CNN. May 21, 2012. 
  15. ^ Time. 7 August 2013 http://nation.time.com/2013/08/07/the-hidden-hand-squeezing-texas-supply-of-execution-drugs/ |url= missing title (help). 
  16. ^ "Texas executes Yokamon Hearn with pentobarbitol". BBC News. 18 July 2012. 
  17. ^ "Texas executes Yokamon Hearn". Retrieved 20 July 2012. 
  18. ^ http://www.chicagotribune.com/news/chi-joseph-paul-franklin-execution-20131120,0,4051870.story[dead link]
  19. ^ http://news.yahoo.com/missouri-executes-serial-killer-franklin-122636393.html
  20. ^ http://www.christianpost.com/news/joseph-paul-franklin-executed-first-mo-inmate-killed-using-pentobarbital-109150/
  21. ^ Knodell, R. G.; Spector, M. H.; Brooks, D. A.; Keller, F. X.; Kyner, W. T. (1980). "Alterations in pentobarbital pharmacokinetics in response to parenteral and enteral alimentation in the rat". Gastroenterology 79 (6): 1211–1216. PMID 6777235.  edit
  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.  edit
  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