Thiopental

Thiopental

Clinical data
Routes of administration	Oral, intravenous
ATC code	N01AF03 (WHO) N05CA19 (WHO)
Legal status
Legal status	US: Schedule III
Pharmacokinetic data
Elimination half-life	5.89-26 hours
Identifiers
IUPAC name sodium 5-ethyl-5-(2-methylpentyl)-4,6-dioxo- -1,4,5,6-tetrahydropyrimidine-2-thiolate
CAS Number	76-75-5
PubChem CID	3000714
DrugBank	APRD00660
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C11H17N2NaO2S
Molar mass	264.321 g/mol

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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.

Barbiturates

Main article: Barbiturate

Barbiturates are a class of drugs that act on the GABA_A receptor in the brain and spinal cord. The GABA_A receptor is an inhibitory channel which decreases neuronal activity and the barbiturates enhance the inhibitory action of the GABA_A receptor. Barbiturates, benzodiazepines, and alcohol all bind to the GABA_A 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.

Uses

Anesthesia

Thiopental is an ultra-short acting barbiturate and is most commonly used in the induction phase of general anesthesia. Following intravenous 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.
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.
Thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays zero-order elimination kinetics, leading to a long period before consciousness is regained. Instead, anesthesia is usually maintained with an 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 half-life, consciousness would take a long time to return.

In veterinary medicine, thiopental is also used to induce 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 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 in reducing intracranial pressure.

Euthanasia

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.

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.[2]

Lethal injection

Along with pancuronium bromide and potassium chloride, thiopental is used in 37 states of the 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.

Truth serum

Thiopental is still used in some places as a truth serum. 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.

Psychiatry

Psychiatrists have used thiopental to desensitize patients with phobias,[3] and to "facilitate the recall of painful repressed memories."[4] One psychiatrist who worked with thiopental is Professor Jan Bastiaans, who used this procedure to help release trauma in victims of the Nazis.[5]

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, 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.

Dosage

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.

Side effects

As with nearly all anesthetic drugs, 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, 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 molecule of thiopental contain sulfur atom, it is not a sulphonamide, 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.

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 in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia. Three months later, Dr. John S. Lundy started a clinical trial of thiopental at the Mayo Clinic at the request of Abbott.

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". Thiopentone anaesthesia was in its early days, but nevertheless only 13 of 344 wounded admitted to the Tripler Army Hospital did not survive.

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.

External links

• PubChem Substance Summary: Thiopental
• Pentothal Abbott Laboratories. 1993.