Thiopental

Structural formula
	Structural formula without stereochemistry
General
Non-proprietary name	Thiopental
other names	( RS ) -5-ethyl-5- (1-methylbutyl) -2-thioxo-1,3-dihydropyrimidine-4,6-dione ( IUPAC ); (±) -5-Ethyl-5- (1-methylbutyl) -2-thioxo-1,3-dihydropyrimidine-4,6-dione;
Molecular formula	C 11 H 18 N 2 O 2 S (thiopental) ; C 11 H 17 N 2 NaO 2 S (thiopental sodium salt ) ;
Brief description	yellowish-white, hygroscopic , unpleasant garlic-like smelling powder (thiopental sodium salt)
External identifiers / databases
EC number	200-984-3
ECHA InfoCard	100,000,896
PubChem	3000715
ChemSpider	2272258
DrugBank	DB00599
Wikidata	Q55186498
Drug information
ATC code	N05 CA19 ; N01 AF03 ;
Drug class	Barbiturates , injection anesthetics
Mechanism of action	Inhibition of the reticular formation
properties
Molar mass	242.34 g · mol -1 (thiopental) ; 264.32 g · mol -1 (thiopental sodium salt) ;
Physical state	firmly
Melting point	157-161 ° C
pK s value	7.55 (20 ° C)
solubility	Water: 96 mg l −1 (25 ° C); soluble in water and ethanol , insoluble in diethyl ether , benzene and ligroin (monosodium salt) ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302
	P: no P-phrases
Toxicological data	110 mg kg −1 ( LD 50 , mouse , ip )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Thiopental (trade name Trapanal ), also Pentothal , as the sodium salt sodium pentothal, is a short-acting hypnotic (sleeping aid) from the series of barbiturates without analgesic effects. It was developed by Ernest H. Volwiler and Donalee L. Tabern for Abbott Laboratories in the early 1930s .

synthesis

Thiopental can be made from diethyl malonate . After two alkylations with 2-bromopentane and bromoethane , the reaction of diethyl ethyl (1-methylbutyl) malonate and thiourea results in thiopental.

Thiopental synthesis

Clinical information

Thiopental is primarily used in anesthesia to induce anesthesia in uncomplicated - i.e. not heart or lung disease - patients. Moreover, it is in the intensive care isolated as a continuous infusion, as ultima ratio (last resort) to reduce intracranial pressure or to break through a seizure ( status epilepticus ).

Dosage and properties

Dosage see red list according to HWG . Onset of action: 20–50 s, duration of action 5–15 min. Elimination half-life 5–10 h, distribution half-life 8.5 min.

Contraindications

Administration is contraindicated in severe liver and kidney disorders, heart failure , porphyria, aortic stenosis, state of shock and barbiturate allergy.

Side effects

Respiratory depression to respiratory standstill (apnea), cramping of the muscles around the airways ( bronchospasm ) and histamine release , drop in blood pressure, pronounced venodilation ( vasodilation of the veins ), reflexive acceleration of the pulse (reflex tachycardia ) with an increase in myocardial oxygen consumption and venous irritation.

Because thiopental has a strongly alkaline reaction (pH value of an aqueous solution around 10.5), accidental paravenous or arterial injection can cause tissue damage and even necrosis . This causes severe pain and threatens the loss of extremities.

Like all barbiturates, thiopental does not have an analgesic effect, so there is a risk of hyperalgesia (excessive sensitivity to pain) in the sub-narcotic dose range .

Pharmacological information

Due to its agonistic effect on the β subunit of the GABA _A receptor, thiopental leads to increased entry of chloride ions and thus to hyperpolarization of nerve cells. In higher doses, it nonselectively suppresses processes in the central nervous system .

After intravenous administration, thiopental binds to a high percentage of plasma proteins. It is distributed in the body primarily to organs with a strong blood supply, then in the central nervous system and finally in the muscles and later in the fatty tissue. There is an equilibrium distribution between the plasma and the muscles. This - and not the balance between plasma and adipose tissue - is decisive for the effective duration of the anesthesia. Therefore, the dose should never be increased in obese patients. Since thiopental eventually accumulates in adipose tissue, repeated administration can lead to accumulation.

Thiopental has a half-life of five to six hours and is metabolized in the body to pentobarbital . Structurally, thiopental and pentobarbital only differ at the C2 atom: in thiopental there is a sulfur atom, in pentobarbital there is an oxygen atom.

Use in executions

In the USA, thiopental is used, among other things, to prepare for execution by lethal injection, and in December 2009 in Ohio for the first time for the execution itself.

On January 24, 2011, the Association of Research-Based Pharmaceutical Companies in Germany announced that its member companies would no longer respond to delivery inquiries from the USA in order to rule out the use of thiopental that could be interpreted as problematic.

On December 16, 2011, an EU- wide uniform export license requirement for thiopental and all other short and medium-term barbituric acids came into force. Since then, thiopental sodium can only be exported from the EU with a special permit. The regulation goes back to an initiative of human rights groups with the support of the then German Minister for Economic Affairs Philipp Rösler . As health minister, he had already asked the German drug manufacturers not to sell the drug in the USA. The US manufacturer Hospira no longer makes thiopental available for executions; Production and sales were discontinued in January 2011.

Trade names

Monopreparations

Pentothal (CH), Trapanal (D), various generics (D, A)

literature

Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , pp. 16-19.

Web links

Commons : Thiopental - collection of images, videos and audio files

Entry on thiopental at Vetpharm, accessed on April 18, 2012.

Individual evidence

↑ ^a ^b ^c Entry on thiopental. In: Römpp Online . Georg Thieme Verlag, accessed on November 12, 2014.
↑ ^a ^b ^c Entry on thiopental in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b data sheet (±) -Thiopental at Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).
↑ translation of the original patent CN201110443500 from Chinese accessed on February 7, 2020
↑ ^a ^b ^c [[Ernst Mutschler (pharmacologist) |]], Monika Schäfer-Korting u. a .: Textbook of pharmacology and toxicology . 8th, completely revised and expanded edition. Wissenschaftliche Verlagsgesellschaft Stuttgart 2001. ISBN 3-8047-1763-2 . P. 281.
^ HW Striebel, K. Eyrich: Operative Intensive Care Medicine . Schattauer Verlag 2007. ISBN 978-3-7945-2480-8 , p. 623.
↑ Article in Abendblatt.de from December 9, 2009 .
↑ Article on taz.de from January 24, 2011 .
↑ G. Bohsem: EU restricts delivery of lethal injection substance. In: Süddeutsche Zeitung . December 11, 2011, accessed December 12, 2011 .

↑ No poison for US lethal injections: Germany says no. In: Doctors newspaper online. January 24, 2011, archived from the original on October 6, 2012 ; Retrieved December 12, 2011 .

[RÖMPP_Online-1] Entry on thiopental. In: Römpp Online . Georg Thieme Verlag, accessed on November 12, 2014.

[ChemIDplus-2] Entry on thiopental in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[sigma-3] ta sheet (±) -Thiopental at Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).

[4] translation of the original patent CN201110443500 from Chinese accessed on February 7, 2020

[Mutschler-5] [[Ernst Mutschler (pharmacologist) |]], Monika Schäfer-Korting u. a .: Textbook of pharmacology and toxicology . 8th, completely revised and expanded edition. Wissenschaftliche Verlagsgesellschaft Stuttgart 2001. ISBN 3-8047-1763-2 . P. 281.

[6] HW Striebel, K. Eyrich: Operative Intensive Care Medicine . Schattauer Verlag 2007. ISBN 978-3-7945-2480-8 , p. 623.

[Abendblatt-7] Article in Abendblatt.de from December 9, 2009 .

[Taz-8] Article on taz.de from January 24, 2011 .

[9] G. Bohsem: EU restricts delivery of lethal injection substance. In: Süddeutsche Zeitung . December 11, 2011, accessed December 12, 2011 .

[10] No poison for US lethal injections: Germany says no. In: Doctors newspaper online. January 24, 2011, archived from the original on October 6, 2012 ; Retrieved December 12, 2011 .