Sodium thiopental
Clinical data | |
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Trade names | Pentothal, Trapanal |
Other names | Truth serum, thiopentone, thiopental |
AHFS/Drugs.com | Monograph |
Pregnancy category |
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Routes of administration | Intravenous (most common), oral, or rectal |
Drug class | Barbiturate |
ATC code | |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Protein binding | 80% |
Metabolism | Liver |
Metabolites | Pentobarbital, others |
Onset of action | 30–45 seconds |
Elimination half-life | 5.5[2]–26 hours[3] |
Duration of action | 5–10 minutes |
Identifiers | |
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JSmol) | |
Chirality | Racemic mixture |
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Sodium thiopental, also known as Sodium Pentothal (a trademark of
Uses
Anesthesia
Sodium thiopental is an ultra-short-acting
A normal dose of sodium thiopental (usually 4–6 mg/kg) given to a pregnant woman for operative delivery (caesarean section) rapidly makes her unconscious, but the baby in her uterus remains conscious. However, larger or repeated doses can depress the baby's consciousness.[11]
Sodium thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays
In
Medically-induced coma
In addition to anesthesia induction, sodium thiopental was historically used to induce medical comas.[13] It has now been superseded by drugs such as propofol because their effects wear off more quickly than thiopental. Patients with
Status epilepticus
In refractory status epilepticus, thiopental may be used to terminate a seizure.
Euthanasia
Sodium thiopental is used intravenously for the purposes of euthanasia. In both Belgium and the Netherlands, where active euthanasia is allowed by law, the standard protocol recommends sodium thiopental as the ideal agent to induce coma, followed by pancuronium bromide to paralyze muscles and stop breathing.[17]
Intravenous administration is the most reliable and rapid way to accomplish euthanasia. Death is quick. A coma is first induced by intravenous administration of 20 mg/kg thiopental sodium (Nesdonal) in a small volume (10 mL physiological saline). Then, a triple dose of a non-depolarizing
Lethal injection
Along with pancuronium bromide and potassium chloride, thiopental is used in 34 states of the US to execute prisoners by lethal injection. A very large dose is given to ensure rapid loss of consciousness. Although death usually occurs within ten minutes of the beginning of the injection process, some have been known to take longer.[18] The use of sodium thiopental in execution protocols was challenged in court after a study in the medical journal The Lancet reported autopsies of executed inmates showed the level of thiopental in their bloodstream was insufficient to cause unconsciousness although this is dependent on different factors and not just on the drug itself.
On December 8, 2009, Ohio became the first state to use a single dose of sodium thiopental for its capital execution, following the failed use of the standard three-drug cocktail during a recent execution, due to inability to locate suitable veins. Kenneth Biros was executed using the single-drug method.[19]
Washington State became the second state in the US to use the single-dose sodium thiopental injections for executions. On September 10, 2010, the execution of Cal Coburn Brown was the first in the state to use a single-dose, single-drug injection. His death was pronounced approximately one and a half minutes after the intravenous administration of five grams of the drug.[20]
After its use for the execution of Jeffrey Landrigan in the US, the United Kingdom introduced a ban on the export of sodium thiopental in December 2010,[21] after it was established that no European supplies to the US were being used for any other purpose.[22] The restrictions were based on "the European Union Torture Regulation (including licensing of drugs used in execution by lethal injection)".[23] From 21 December 2011, the EU extended trade restrictions to prevent the export of certain medicinal products for capital punishment, stating that "the Union disapproves of capital punishment in all circumstances and works towards its universal abolition".[24]
Truth serum
Thiopental is still used in some places as a truth serum to weaken the resolve of a subject and make the individual more compliant to pressure.[25] Barbiturates decrease both higher cortical brain function and inhibition. It is hypothesized that because lying is a more mentally involving process than telling the truth, suppression of the higher cortical functions may lead to the uncovering of the truth. The drug tends to make subjects verbose and cooperative with interrogators; however, the reliability of confessions made under thiopental is questionable.[26]
Psychiatry
Psychiatrists have used thiopental to desensitize patients with
Mechanism of action
Sodium thiopental is a member of the barbiturate class of drugs, which are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is one of several representatives. This superfamily of ion channels includes the neuronal nicotinic acetylcholine receptor (nAChR), the 5-HT3 receptor, the glycine receptor and others. Surprisingly, while GABAA receptor currents are increased by barbiturates (and other general anesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR are blocked by clinically relevant anesthetic concentrations of both sodium thiopental and pentobarbital.[30] Such findings implicate (non-GABAergic) ligand-gated ion channels, e.g. the neuronal nAChR, in mediating some of the (side) effects of barbiturates.[31] The GABAA receptor is an inhibitory channel that decreases neuronal activity, and barbiturates enhance the inhibitory action of the GABAA receptor.[32]
Controversies
Following a shortage that led a court to delay an execution in California, a company spokesman for Hospira, the sole American manufacturer of the drug, objected to the use of thiopental in lethal injection. "Hospira manufactures this product because it improves or saves lives, and the company markets it solely for use as indicated on the product labeling. The drug is not indicated for capital punishment and Hospira does not support its use in this procedure."[33] On January 21, 2011, the company announced that it would stop production of sodium thiopental from its plant in Italy, because it could not provide Italian authorities with guarantees that exported doses would not be used in executions. According to a company spokesperson, Italy was the only viable place where it could produce the drug, leaving the US without a supplier.[34]
In October 2015 the U.S. Food and Drug Administration confiscated an overseas shipment of thiopental destined for the states of Arizona and Texas. FDA spokesman Jeff Ventura said in a statement, "Courts have concluded that sodium thiopental for the injection in humans is an unapproved drug and may not be imported into the country".[35]
Metabolism
Thiopental rapidly and easily crosses the
Dosage
The usual dose range for induction of anesthesia using thiopental is from 3 to 6 mg/kg; however, there are many factors that can alter this. Premedication with sedatives such as
Side effects
As with nearly all
Although each molecule of thiopental contains one sulfur atom, it is not a sulfonamide, and does not show the allergic reactions of sulfa/sulpha drugs.
Contraindications
Thiopental should be used with caution in cases of
Co-administration of
History
Sodium thiopental was discovered in the early 1930s by Ernest H. Volwiler and Donalee L. Tabern, working for Abbott Laboratories. It was first used in human beings on March 8, 1934, by Dr. Ralph M. Waters[43] in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia.[44] Three months later,[45] Dr. John S. Lundy started a clinical trial of thiopental at the Mayo Clinic at the request of Abbott.[46] Abbott continued to make the drug until 2004, when it spun off its hospital-products division as Hospira.
Thiopental is famously associated with a number of anesthetic deaths in victims of the
See also
References
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
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- ^ hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
- ^ "Death Penalty Opposition: EU Set to Ban Export of Drug Used in US Executions". Spiegel Online International. Retrieved 23 January 2014.
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- ^ Takeko T. "TRAUMA.ORG: Critical Care: Barbiturate Coma". trauma.org. Archived from the original on 19 August 2016. Retrieved 18 August 2016.
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- ^ Trickey D. "Anesthetic Management of Head-injured Patients". www.amcresidents.com. Archived from the original on 2020-10-18. Retrieved 2020-10-13.
- ^ a b Royal Dutch Society for the Advancement of Pharmacy (1994). "Administration and Compounding of Euthanasic Agents". The Hague. Archived from the original on 2008-08-21. Retrieved 2008-07-18.
- ^ "Ohio executes inmate with 1-drug lethal injection". Associated Press. December 2001. Retrieved 2009-12-08.
- ^ Martinez E (8 December 2009). "Kenneth Biros Execution: Ohio Man First to Die Under 1-Drug Thiopental Sodium Method". CBS News.
- ^ Sullivan J (10 September 2010). "Killer on death row 16-1/2 years is executed". The Seattle Times.
- ^ "Drug sold in UK to be used for execution in Georgia". bbc.co.uk. BBC News. 24 January 2011. Retrieved 18 August 2016.
- ^ Casciani D (29 November 2010). "US lethal injection drug faces UK export restrictions". bbc.co.uk. BBC News. Retrieved 18 August 2016.
- ^ "Controls on torture goods - Detailed guidance - GOV.UK". gov.uk. Retrieved 18 August 2016.
- ^ "EU Council Regulation (EU) No 1352/2011".
- ^ "Truth serum used on 'serial child killers'". Sydney Morning Herald. Reuters. January 12, 2007.
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- TIME. February 24, 1958.
- ^ Snelders S (1998). "The LSD Therapy Career of Jan Bastiaans, M.D". Newsletter of the Multidisciplinary Association for Psychedelic Studies. 8 (1). Multidisciplinary Association for Psychedelic Studies: 18–20.
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- ^ "Anesthesia and Analgesia". University of Virginia School of Medicine. Archived from the original on 2007-05-18. Retrieved 2007-08-05.
- ^ Pilkington E (2010-09-28). "US executions delayed by shortage of death penalty drug". Guardian. Retrieved 2022-06-18.
- ^ Welsh-Huggins A (January 21, 2011). "Key death penalty drug discontinued by U.S. maker". NBC News. Retrieved 2022-06-18.
- ^ Solomon D (October 27, 2015). "The FDA Confiscated A Supply Of Execution Drugs Texas Is Thought To Have Imported Illegally". Texas Monthly. Retrieved March 10, 2021.
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- ^ "PENTOTHAL". RXList. WebMD. 15 November 2021. Retrieved 18 June 2023.
- ^ "Pentothal (thiopental)". eMedicineHealth. 12 April 2009. Archived from the original on 18 January 2015. Retrieved 15 October 2010.
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- PMID 16953192.
- ^ "This Month in Anesthesia History: March". Anesthesia History Association. Archived from the original on 2011-05-01.
- ^ Steinhaus JE (September 2001). "The Investigator and His 'Uncompromising Scientific Honesty'". ASA Newsletter. 65 (9). American Society of Anesthesiologists: 7–9. Archived from the original on 2011-05-13.
- PMID 5175948. Archived from the originalon 2011-05-01.
- ISBN 0-8240-6525-5. Archived from the original(PDF) on 2011-05-01.
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External links
- PubChem Substance Summary: Thiopental
- Vassallo, Susi, M.D. "Thiopental in Lethal Injection" (Archive). Fordham Urban Law Journal. Vol. 35, issue 4. June 18, 2008. pp. 957–968.