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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.^{[citation needed]} 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. The unintentional death of Marilyn Monroe has been attributed to an overdose of Nembutal.^[1]

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.

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 relaxant previously used as one component in a three-drug cocktail.^[13]

In October 2013, Missouri changed its protocols to allow for a compounded pentobarbital to be used in a lethal dose for executions.^[14] On November 20, 2013, Joseph Paul Franklin was executed by the state of Missouri.^[15] He was the first inmate executed in three years in the state and the first to die by a single dose of 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 (not 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

Pentobarbital

Clinical data
Trade names	Nembutal
AHFS/Drugs.com	Monograph
MedlinePlus	a682416
License data	US FDA: Pentobarbital
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	N05CA01 (WHO) QN51AA01 (WHO)
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
Bioavailability	70–90% (oral); 90% (rectal)
Protein binding	20–45%
Metabolism	Liver
Elimination half-life	15–48 hours
Excretion	Kidney
Identifiers
IUPAC name 5-Ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
CAS Number	76-74-4 Y
PubChem CID	4737
IUPHAR/BPS	5480
DrugBank	DB00312 Y
ChemSpider	4575 Y
UNII	I4744080IR
KEGG	D00499 Y
ChEBI	CHEBI:7983 Y
ChEMBL	ChEMBL448 Y
ECHA InfoCard	100.000.895
Chemical and physical data
Formula	C11H18N2O3
Molar mass	226.27
3D model (JSmol)	Interactive image
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) Y Key:WEXRUCMBJFQVBZ-UHFFFAOYSA-N Y
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