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| {{drugbox |
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| | IUPAC_name = sodium 5-ethyl-5-(2-methylpentyl)-4,6-dioxo-<br>-1,4,5,6-tetrahydropyrimidine-2-thiolate
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| | image = tiopental.jpg
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| | image2 = Sodium-thiopental-3D-vdW-2.jpg
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| | width = 113px
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| | CAS_number = 76-75-5
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| | ATC_prefix = N01
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| | ATC_suffix = AF03
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| | ATC_supplemental = {{ATC|N05|CA19}}
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| | PubChem = 3000714
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| | DrugBank = APRD00660
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| | C = 11 | H = 17 | N = 2 | Na = 1 | O = 2 | S = 1
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| | molecular_weight = 264.321 g/mol
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| | bioavailability =
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| | metabolism =
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| | elimination_half-life = 5.89<ref>Russo H, Bres J, Duboin MP, Roquefeuil B. "Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients". ''Eur J Clin Pharmacol'' 1995; 49(1–2):127–37. PMID: 8751034</ref>-26 hours<ref>Morgan DJ, Blackman GL, Paull JD, Wolf LJ. "Pharmacokinetics and plasma binding of thiopental. II: Studies at cesarean section". ''Anesthesiology'' 1981 Jun;54(6):474–80. PMID 7235275</ref>
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| | excretion =
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| | pregnancy_category =
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| | legal_US = Schedule III
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| | routes_of_administration = Oral, intravenous
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| }}
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| {{CMG}}
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| '''Sodium thiopental''', better known as '''Sodium Pentothal''' (a [[trademark]] of [[Abbott Laboratories]]), '''thiopental''', '''thiopentone''' '''sodium''', or '''trapanal''', is a rapid-onset short-acting [[barbiturate]] [[general anaesthetic]]. It is an intravenous ultra-short-acting barbiturate. Sodium thiopental is a depressant and is sometimes used during interrogations - not to cause pain (in fact, it may have just the opposite effect), but to weaken the resolve of the subject and make him or her more compliant to pressure.
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| <!--==Mechanism of Action==-->
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| ==Barbiturates==
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| {{main|Barbiturate}}
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| Barbiturates are a class of drugs that act on the [[GABA A receptor|GABA<sub>A</sub> receptor]] in the brain and spinal cord. The GABA<sub>A</sub> receptor is an inhibitory channel which decreases neuronal activity and the barbiturates enhance the inhibitory action of the GABA<sub>A</sub> receptor. Barbiturates, [[benzodiazepine]]s, and [[alcohol]] all bind to the GABA<sub>A</sub> receptor, but the barbiturates bind with the highest affinity with longer receptor binding half-lives. This explains why overdoses of barbiturates may be lethal whereas overdoses of benzodiazepines alone are typically not lethal. Another explanation is that barbiturates can activate GABA receptors in the absence of the GABA molecule, whereas benzodiazepines need GABA to be present to have an effect: this may explain the more widespread effects of barbiturates in the central nervous system. Barbiturates have [[anesthetic]], [[sedative]], and [[hypnotic]] properties. Barbiturates do not have [[analgesic]] effects.<ref>{{cite web |url=http://www.healthsystem.virginia.edu/internet/ccm/Anesth/aneshome.cfm |title=ANESTHESIA AND ANALGESIA |accessdate=2007-08-05 |format= |work=}}</ref>
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| ==Uses==
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| ===Anesthesia===
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| Thiopental is an ultra-short acting barbiturate and is most commonly used in the induction phase of [[general anaesthesia|general anesthesia]]. Following [[intravenous therapy|intravenous]] [[Injection (medicine)|injection]] the drug rapidly reaches the brain and causes unconsciousness within 30–45 seconds. At one minute, the drug attains a peak concentration of about 60% of the total dose in the brain. Thereafter, the drug distributes to the rest of the body and in about 5–10 minutes the concentration is low enough in the brain such that consciousness returns.<br />
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| A normal dose of thiopental (usually 4-6 mg/kg) given to a pregnant woman for operative delivary ([[ceasarian section]]) rapidly makes her unconcious, but her baby in her [[uterus]] remains concious. However, larger or repeated doses can depress the baby.<br />
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| Thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays [[Biological half-life#Zero-order elimination|zero-order elimination kinetics]], leading to a long period before consciousness is regained. Instead, anesthesia is usually maintained with an [[Inhalational anaesthetic|inhaled anesthetic]] (gas) agent. Inhaled anesthetics are eliminated relatively quickly, so that stopping the inhaled anesthetic will allow rapid return of consciousness. Thiopental would have to be given in large amounts to maintain an anesthetic plane, and because of its 11.5–26 hour [[Biological half-life|half-life]], consciousness would take a long time to return.<ref>{{cite journal |author=Morgan DJ, Blackman GL, Paull JD, Wolf LJ |title=Pharmacokinetics and plasma binding of thiopental. II: Studies at cesarean section |journal=Anesthesiology |volume=54 |issue=6 |pages=474–80 |year=1981 |pmid=7235275 |doi=}}</ref>
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| In [[veterinary medicine]], thiopental is also used to induce [[Veterinary anesthesia|anesthesia in animals]]. Since thiopental is redistributed to fat, certain breeds of dogs, primarily the [[sight hounds]] can have prolonged recoveries from thiopental due to their lack of body fat and lean body mass. Thiopental is always administered intravenously, as it can be fairly irritating; severe tissue necrosis and sloughing can occur if it is injected incorrectly into the tissue around a vein.
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| ===Medically induced coma===
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| In addition to anesthesia induction, thiopental can be used to induce medical comas. Even though the drug is described as an ultra-short acting barbiturate, the drug's half-life is much longer and giving a larger dose ensures adequate concentrations in the brain to maintain anesthesia. Patients with brain swelling, causing elevation of the intracranial pressure, either secondary to trauma or following surgery may benefit from this drug. Thiopental, and the barbiturate class of drugs, decrease neuronal activity and therefore decrease the production of osmotically active metabolites which in turn decrease swelling. Patients with significant swelling have improved outcomes following the induction of coma. Reportedly, thiopental has been shown to be superior to [[pentobarbital]]<ref>Pérez-Bárcena J, Barceló B, Homar J, Abadal JM, Molina FJ, de la Peña A, Sahuquillo J, Ibáñez J. "Comparison of the effectiveness of pentobarbital and thiopental in patients with refractory intracranial hypertension. Preliminary report of 20 patients]" [Article in Spanish] ''Neurocirugia (Astur).'' 2005 Feb;16(1):5–12; discussion 12-3. PMID 15756405 [http://www.revistaneurocirugia.com/web/artics/v16n1/1.pdf Fulltext]</ref> in reducing intracranial pressure.
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| ===[[Euthanasia]]===
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| Thiopental is used intravenously for the purposes of euthanasia. The Belgians and the Dutch have created a protocol that recommends sodium thiopental as the ideal agent to induce coma followed by [[pancuronium bromide]].<ref>{{cite web |url=http://www.wweek.com/html/euthanasics.html |title=euthanasics |accessdate=2007-08-05 |format= |work=}}</ref>
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| :Intravenous administration is the most reliable and rapid way to accomplish euthanasia and therefore can be safely recommended. 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 intravenous dose of a non-depolarizing neuromuscular muscle relaxant is given, such as 20 mg pancuronium dibromide (Pavulon) or 20 mg [[vecuronium bromide]] (Norcuron). The muscle relaxant should preferably be given intravenously, in order to ensure optimal availability. Only for [[pancuronium]] dibromide (Pavulon) are there substantial indications that the agent may also be given intramuscularly in a dosage of 40 mg.[http://www.wweek.com/html/euthanasics.html]
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| ===Lethal injection===
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| Along with [[pancuronium bromide]] and [[potassium chloride]], thiopental is used in 37 states of the [[United States|U.S.]] to execute prisoners by [[lethal injection]]. A megadose is given which places the subject into a rapidly induced coma. Executions using the three drug combination are usually effective in approximately 10 minutes, but have been known to take several times this length. The use of thiopental alone is hypothesized to cause death in approximately 45 minutes.<ref>{{cite web |url=http://www.latimes.com/news/local/la-me-morales21feb21,0,246025.story?coll=la-home-headlines |title=Los Angeles Times |accessdate=2007-08-05 |format= |work=}}</ref>
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| ===Truth serum===
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| Thiopental is still used in some places as a [[truth drug|truth serum]].<ref>[http://www.smh.com.au/news/world/truth-serum-used-on-serial-child-killers/2007/01/12/1168105166282.html Sydney Morning Herald], Truth serum used on 'serial child killers', January 12, 2007, Reuters.</ref> The barbiturates as a class decrease higher cortical brain functioning. Psychiatrists hypothesize that because lying is more complex than telling the truth, suppression of the higher cortical functions may lead to the uncovering of the "truth". However, the reliability of confessions made under thiopental is dubious; the drug tends to make subjects chatty and cooperative with interrogators, but a practiced liar or someone who has a false story firmly established would still be quite able to lie while under the influence of the drug.
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| ===Psychiatry===
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| Psychiatrists have used thiopental to desensitize patients with phobias,[http://ajp.psychiatryonline.org/cgi/content/abstract/137/12/1580] and to "facilitate the recall of painful repressed memories."[http://www.time.com/time/magazine/article/0,9171,863001,00.html] One psychiatrist who worked with thiopental is Professor Jan Bastiaans, who used this procedure to help release trauma in victims of the [[Nazi]]s.[http://www.maps.org/news-letters/v08n1/08118sne.html]
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| ==Metabolism==
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| As with all lipid soluble anaesthetic drugs, the short duration of action of STP is almost entirely due to its redistribution away from central circulation towards muscle and fat tissue. Once redistributed the free fraction in the blood is metabolised in the liver. Sodium thiopental is mainly metabolized to [[pentobarbital]],<ref>WINTERS WD, SPECTOR E, WALLACH DP, SHIDEMAN FE. "Metabolism of thiopental-S35 and thiopental-2-C14 by a rat liver mince and identification of pentobarbital as a major metabolite." ''Journal of Pharmacology Experimental Therapeutics.'' 1955 Jul;114(3):343–57. PMID 13243246</ref> 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.<ref>Bory C, Chantin C, Boulieu R, Cotte J, Berthier JC, Fraisse D, Bobenrieth MJ. "[Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry]" [Article in French] ''C R Acad Sci III.'' 1986;303(1):7–12. PMID 3093002</ref>
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| ==Dosage==
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| The usual dose range for induction of anesthesia using thiopentone is from 3 to 7 mg/kg; however, there are many factors that can alter this. Premedication with sedatives such as [[benzodiazepines]] or [[clonidine]] will reduce requirements, as do specific disease states and other patient factors.
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| ==Side effects==
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| As with nearly all [[anesthesia|anesthetic]] [[Medication|drug]]s, thiopental causes cardiovascular and respiratory depression resulting in [[hypotension]], [[apnea]] and [[airway]] obstruction. For these reasons, only suitably trained medical personnel should give thiopental in an environment suitably equipped to deal with these effects. Side effects include headache, [[delirium|emergence delirium]], prolonged [[somnolence]] and [[nausea]]. Intravenous administration of sodium thiopental is followed instantly by an odor sensation, sometimes described as being similar to rotting onions. The hangover effects may last up to 36 hours.
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| Although [[molecule]] of thiopental contain [[sulfur]] atom, it is not a [[sulphonamide]], and does not show allergic reactions of sulfa/sulpha drugs.
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| ==Drug interaction==
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| Co-administration of [[pentoxifylline]] and thiopental causes death by acute [[pulmonary oedema]] in rats. This pulmonary oedema was not mediated by [[cardiac failure]] or by [[pulmonary hypertension]] but was due to increased pulmonary vascular permeability.<ref> Pereda J, Gómez-Cambronero L, Alberola A, Fabregat G, Cerdá M, Escobar J, Sabater L, García-de-la-Asunción J, Viña J, Sastre J.
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| Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain. Br J Pharmacol. 2006 Oct;149(4):450–5. Epub 2006 Sep 4.PMID: 16953192.</ref>
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| ==History==
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| 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]]<ref>[http://www.anes.uab.edu/march.htm This Month in Anesthesia History: March]</ref> in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia.<ref>Steinhaus, John E. [http://www.asahq.org/Newsletters/2001/09_01/steinhaus.htm The Investigator and His ‘Uncompromising Scientific Honesty’] American Society of Anesthesiologists. ''NEWSLETTER.'' September 2001, Volume 65, Number 9.</ref> Three months later,<ref>[http://www.aana.com/archives/imagine/1997/08imagine97.asp Imagining in Time—''From this point in time: Some memories of my part in the history of anesthesia—John S. Lundy, MD''] August 1997, AANA Archives-Library</ref> Dr. [[John S. Lundy]] started a clinical trial of thiopental at the [[Mayo Clinic]] at the request of Abbott.<ref>[http://www.aana.com/archives/pdf/0008CHP7.pdf History of Anesthesia with Emphasis on the Nurse Specialist] ''Archives of the American Association of Nurse Anesthetists.'' 1953</ref>
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| It is famously associated with a number of anesthetic deaths in victims of the attack on [[Pearl Harbor]]. These deaths, relatively soon after its discovery, were due to excessive doses given to shocked trauma patients. Evidence has however become available through freedom of information legislation and has been reviewed in the "British Journal of Anaesthesia".<ref name="pmid7547061">{{cite journal |author=Bennetts FE |title=Thiopentone anaesthesia at Pearl Harbor |journal=British journal of anaesthesia |volume=75 |issue=3 |pages=366–8 |year=1995 |pmid=7547061 |doi=}}</ref> Thiopentone anaesthesia was in its early days, but nevertheless only 13 of 344 wounded admitted to the Tripler Army Hospital did not survive.
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| Thiopental is still rarely encountered as a [[recreational drug]], usually stolen from veterinarians or other legitimate users of the drug, however more common sedatives such as [[benzodiazepines]] are usually preferred, and abuse of thiopental tends to be uncommon and opportunistic.
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| ==References==
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| {{Reflist|2}}
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| == External links ==
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| * [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=149220 PubChem Substance Summary: Thiopental]
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| * [http://www.hospira.com/Files/PDF/Pentothal-PI.pdf Pentothal] Abbott Laboratories. 1993.
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| {{Barbiturates}}
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| {{General anesthetics}}
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| {{Hypnotics and sedatives}}
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| [[Category:Anesthetics]]
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| [[Category:Barbiturates]]
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| [[Category:Lethal injection components]]
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| [[Category:Sodium compounds]]
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| [[Category:Thiobarbiturates]]
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