Natriumthiopental

2009-12-08T23:38:05Z

Xaphnir: Undid revision 330562078 by 207.119.109.114 (talk)

{{redirect|C11H17N2O2S Na|the song by Anthrax|Sound of White Noise}}

{{drugbox | Watchedfields = changed
| verifiedrevid = 268449664
|
| IUPAC_name = (''RS'')-[5-ethyl-4,6-dioxo-5-(pentan-2-yl)-1,4,5,6-tetrahydropyrimidin-2-yl]sulfanide sodium
| image = tiopental.png
| image2 = Sodium-thiopental-3D-vdW-2.png
| width = 113
| CAS_number = 71-73-8
| CASNo_Ref = {{cascite}}
| CAS_supplemental = (sodium salt) 76-75-5 (free acid) 
| ChemSpiderID = 2272257
| ATC_prefix = N01
| ATC_suffix = AF03
| ATC_supplemental = {{ATC|N05|CA19}}
| PubChem = 3000714
| DrugBank = APRD00660
| C = 11 | H = 17 | N = 2 | Na = 1 | O = 2 | S = 1
| molecular_weight = 264.32 g/mol
| bioavailability =
| metabolism =
| elimination_half-life = 5.5<ref>{{cite journal |author=Russo H, Brès J, Duboin MP, Roquefeuil B |title=Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients |journal=Eur. J. Clin. Pharmacol. |volume=49 |issue=1-2 |pages=127–37 |year=1995 |pmid=8751034 |doi= 10.1007/BF00192371|url= |accessdate=2008-07-18}}</ref>-26 hours<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 |month=June |pmid=7235275 |doi= |url= |accessdate=2008-07-18}}</ref>
| excretion =
| pregnancy_category =
| legal_US = Schedule III
| routes_of_administration = Oral, intravenous
}}
'''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]]. 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.<ref name="SMH_truth_serum">[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> Thiopental is a ''core'' medicine in the [[World Health Organization]]'s "[[WHO Model List of Essential Medicines|Essential Drugs List]]", which is a list of minimum medical needs for a basic health care system.<ref name="essentialWHO">{{cite web
| year = March 2005
| url = http://whqlibdoc.who.int/hq/2005/a87017_eng.pdf
| title = WHO Model List of Essential Medicines
| format = PDF
| publisher = World Health Organization
| accessdate = 2006-03-12
}}</ref>


==Barbiturates==
{{Main|Barbiturate}}
Barbiturates are a class of drugs that act on the [[GABA A receptor|GABAA receptor]] in the brain and spinal cord. The GABAA receptor is an inhibitory channel that decreases neuronal activity, and barbiturates enhance the inhibitory action of the GABAA receptor. Barbiturates, [[benzodiazepine]]s, and [[alcohol]] all bind to the GABAA receptor. Barbiturates that act on the barbiturate binding site of the GABAA receptor directly gate the chloride ion channel of the GABAA receptor, whereas benzodiazepines acting on the benzodiazepine site on the GABAA receptor increase the opening frequency of the chloride ion channel. 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]], [[anxiolytic]], [[anticonvulsant]] and [[hypnotic]] properties. Benzodiazepines 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>

==Uses==
===Anesthesia===
Thiopental is an ultra-short-acting barbiturate and has been used commonly in the induction phase of [[general anaesthesia|general anesthesia]]. Its use in the United States and elsewhere has been largely replaced with that of [[propofol]]. 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.{{citation needed|date=December 2009}}

A normal dose of thiopental (usually 4–6 mg/kg) given to a pregnant woman for operative delivery ([[caesarian section]]) rapidly makes her unconscious, but the baby in her [[uterus]] remains conscious. However, larger or repeated doses can depress the baby.{{citation needed|date=December 2009}}

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>

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.

===Medically induced coma===
In addition to anesthesia induction, thiopental was historically used to induce medical [[coma]]s. It has now been superseded by drugs such as [[propofol]].

Thiopental has a long Context Sensitive Half Time (CSHT) meaning infusions saturate peripheral compartments (fat, muscle etc). When the infusion is stopped, the drug re-distributes from the peripheral tissues back into the blood, prolonging the effect.

Thiopental also exhibits [[Rate_law#Zero-order_reactions|zero order kinetics]] at higher doses. The rate of elimination becomes constant.

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 decreases swelling. Patients with significant swelling have improved outcomes following the induction of coma. Reportedly, thiopental has been shown to be superior to [[pentobarbital]]<ref>{{cite journal |author=Pérez-Bárcena J, Barceló B, Homar J, ''et al.'' |title=[Comparison of the effectiveness of pentobarbital and thiopental in patients with refractory intracranial hypertension. Preliminary report of 20 patients] |language=Spanish; Castilian |journal=Neurocirugia (Astur) |volume=16 |issue=1 |pages=5–12; discussion 12–3 |year=2005 |month=February |pmid=15756405 |doi= |url=http://www.revistaneurocirugia.com/web/artics/v16n1/1.pdf |accessdate=2008-07-18}}</ref> in reducing intracranial pressure.

===Euthanasia===
Thiopental is used intravenously for the purposes of [[euthanasia]]. The [[Belgium|Belgian]]s and the [[Netherlands|Dutch]] have created a protocol that recommends sodium thiopental as the ideal agent to induce coma followed by [[pancuronium bromide]].<ref name=euthanasics>{{cite web |url=http://wweek.com/html/euthanasics.html |title=Administration and Compounding of Euthanasic Agents |accessdate=2008-07-18 |author=Royal Dutch Society for the Advancement of Pharmacy |publisher=[[The Hague]] |year=1994}}</ref>

: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.<ref name=euthanasics />

===Lethal injection===
Along with [[pancuronium bromide]] and [[potassium chloride]], thiopental is used in 34 states of the [[United States|U.S.]] to execute prisoners by [[lethal injection]]. A very large dose 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 name="Biros">{{cite web
| year = December 2009
| url = http://news.yahoo.com/s/ap/20091208/ap_on_re_us/us_ohio_execution
| title = Ohio executes inmate with 1-drug lethal injection
| format = HTML
| publisher = AP
| accessdate = 2009-12-08
}}</ref> The use of sodium thiopental has been the cause of current Supreme Court challenges to the lethal injection protocol, after a study in the medical journal [[the Lancet]], where autopsy studies on executed inmates revealed that there was not a high enough concentration of thiopental in their blood to have caused unconsciousness. The exclusion of physicians participating in executions is partly to blame for inept administration of the drugs.{{Citation needed|date=July 2009}}

On December 8, 2009, the State of Ohio became the first 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. The execution took 43 minutes and was concluded at 11:47am, including approximately 30 minutes to complete the process of inserting the needle, and about 10 minutes between administering the single dose and the pronouncement of death.<ref name="Biros"></ref>

===Truth serum===
Thiopental is still used in some places as a [[truth drug|truth serum]]. The barbiturates as a class decrease higher cortical brain functioning. Some 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 relate the falsehood while under the influence of the drug.<ref>{{cite book |author=Anne Bannon; Stevens, Serita Deborah |title=The Howdunit Book of Poisons (Howdunit) |publisher=Writers Digest Books |location=Cincinnati |year=2007 |isbn=1-58297-456-X}}</ref>

===Psychiatry===
Psychiatrists have used thiopental to desensitize patients with phobias,<ref>{{cite journal | url = http://ajp.psychiatryonline.org/cgi/content/abstract/137/12/1580 | title = Behavioral desensitization of phobic anxiety using thiopental sodium | first = T. | last = Pearlman | journal = [[The American Journal of Psychiatry]] | publisher = [[American Psychiatric Association]] | year = 1980 | issue = 137 | pages = 1580–1582}}</ref> and to "facilitate the recall of painful repressed memories."<ref>{{cite news | url = http://www.time.com/time/magazine/article/0,9171,863001,00.html | title = Drugged Future? | date = February 24, 1958 | work = [[TIME]]}}</ref> One psychiatrist who worked with thiopental is the [[Dutch people|Dutch]] Professor Jan Bastiaans, who used this procedure to help release trauma in victims of the [[Nazi]]s.<ref>{{cite journal | url = http://www.maps.org/news-letters/v08n1/08118sne.html | title = The LSD Therapy Career of Jan Bastiaans, M.D. | first = Stephen | last = Snelders | journal = Newsletter of the Multidisciplinary Association for Psychedelic Studies | publisher = [[Multidisciplinary Association for Psychedelic Studies]] | volume = 8 | issue = 1 | year = 1998 | pages = 18–20}}</ref>

==Metabolism==
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>{{cite journal |author=WINTERS WD, SPECTOR E, WALLACH DP, SHIDEMAN FE |title=Metabolism of thiopental-S35 and thiopental-2-C14 by a rat liver mince and identification of pentobarbital as a major metabolite |journal=J. Pharmacol. Exp. Ther. |volume=114 |issue=3 |pages=343–57 |year=1955 |month=July |pmid=13243246 |doi= |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=13243246 |accessdate=2008-07-18}}</ref> 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.<ref>{{cite journal |author=Bory C, Chantin C, Boulieu R, ''et al.'' |title=[Use of thiopental in man. Determination of this drug and its metabolites in plasma and urine by liquid phase chromatography and mass spectrometry] |language=French |journal=C. R. Acad. Sci. III, Sci. Vie |volume=303 |issue=1 |pages=7–12 |year=1986 |pmid=3093002 |doi= |url= |accessdate=2008-07-18}}</ref>

==Dosage==
The usual dose range for induction of anesthesia using thiopental 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.

==Side effects==
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.

Although [[molecules]] of thiopental contain one [[sulfur]] atom, it is not a [[sulfonamide]], and does not show allergic reactions of sulfa/sulpha drugs.

==Drug interaction==
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>{{cite journal |author=Pereda J, Gómez-Cambronero L, Alberola A, ''et al.'' |title=Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats |journal=Br. J. Pharmacol. |volume=149 |issue=4 |pages=450–5 |year=2006 |month=October |pmid=16953192 |pmc=1978439 |doi=10.1038/sj.bjp.0706871 |accessdate=2008-07-18}}</ref>

==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<ref>{{cite web | url = http://www.anesthesia.wisc.edu/AHA/Calendar/March.html | title = This Month in Anesthesia History: March | publisher = Anesthesia History Association}}</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>

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 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=Br J Anaesth |volume=75 |issue=3 |pages=366–8 |year=1995 |month=September |pmid=7547061 |doi= |url=http://bja.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=7547061 |accessdate=2008-07-18}}</ref> Thiopental anaesthesia was in its early days, but nevertheless only 13 of 344 wounded admitted to the [[Tripler Army Medical Center|Tripler Army Hospital]] did not survive.

Thiopental is still rarely used 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 as recreational drugs, and abuse of thiopental tends to be uncommon and opportunistic.

==References==
{{Reflist|2}}

== External links ==
* [http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=149220 PubChem Substance Summary: Thiopental]

{{Barbiturates}}
{{General anesthetics}}
{{Hypnotics and sedatives}}

{{DEFAULTSORT:Sodium Thiopental}}

[[Category:General anesthetics]]
[[Category:Barbiturates]]
[[Category:Lethal injection components]]
[[Category:Sodium compounds]]
[[Category:Thiobarbiturates]]
[[Category:World Health Organization essential medicines]]



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Wikipedia - Benutzerbeiträge [de]

Natriumthiopental