Article: Sodium thiopental

Sodium thiopental
Systematic (IUPAC) name
sodium 5-ethyl-6-oxo-5-pentan- 2-yl-2-sulfanyl-pyrimidin-4-olate
Identifiers
CAS number	76-75-5
ATC code	N01AF03 N05CA19
PubChem	?
DrugBank	APRD00660
Chemical data
Formula	C11H17N2NaO2S
Mol. weight	264.321
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	5.89[1]-26 hours[2]
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	US:Schedule III
Routes	Orally, intravenous

Sodium thiopental also called Sodium Pentothal (a trademark of Abbott Laboratories), thiopental, thiopentone sodium, or trapanal is a rapid-onset, short-acting barbiturate general anesthetic.

Barbiturates

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, yet the barbiturates bind with the highest affinity. This explains why overdoses of barbiturates may be lethal whereas overdoses of benzodiazepines alone are typically not lethal. Barbiturates have anesthetic, sedative, and hypnotic properties. Barbiturates do not have analgesic effects.[2]

Uses

3D model of sodium thiopental

Anesthesia

Thiopental is an ultra-short acting barbiturate and is most commonly used in the induction phase of general anaesthesia. 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 consciouness returns.

Thiopental is not used for the maintenance of anesthesia in surgical procedures because it has a long context-sensitive half-time, leading to a prolonged period before consciousness is regained. Instead, anaesthesia is usually maintained with an inhaled anesthetic agent. This class of drugs has a relatively rapid elimination, 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.[3]

Medical-induced comas

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^[3] in reducing intracranial pressure.

Euthanasia

Thiopental is sometimes used intravenously for the purposes of euthanasia. The Dutch have created a protocol that recommends sodium thiopental as the ideal agent to induce coma followed by pancuronium bromide.[4]

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.[5]

Lethal injection

Along with pancuronium bromide and potassium chloride, thiopental is used in 37 states of the US to execute prisoners by lethal injection. A megadose is given which places the patient 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.^[4]

Truth Serum

Thiopental is still used in some places as a truth serum. The barbiturate drugs as a class decrease higher cortical brain functioning. Since lying is more complex than the truth, suppression of the higher cortical functions may lead to the divulgement of the "truth." Reports indicate that thiopental has been used during the interrogation of Abu Faraj al-Libbi^[5] in Pakistan and Abu Salem in India.

Psychiatry

Psychiatrists and hypnotists have also used thiopental to facilitate the answering of questions. ^{[citation needed]}

Metabolism

Sodium thiopental is mainly metabolized to pentobarbital,^[6] 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.^[7]

Dosage

The usual dose range for induction of anaesthesia using thiopentone is from 3 to 7 mg/kg, however, there are many factors which 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 anaesthetic drugs, thiopental causes cardiovascular and respiratory depression resulting in hypotension, apnea and airway obstruction. For these reasons, only anesthesiologists and other suitably trained doctors should give thiopental in an environment suitably equipped to deal with these effects. Side effects include headache, emergence delirium, prolonged somnolence and nausea. The hangover effects may last up to 36 hours.

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^[8] in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia.^[9] Three months later,^[10] Dr. John S. Lundy started a clinical trial of thiopental at the Mayo Clinic at the request of Abbott.^[11]

It is famously associated with a number of anaesthetic 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.