SODIUM THIOPENTAL

University of the East – Recto, Manila

Science Department

Organic Chemistry

ACH 221/222

Submitted to:

Prof. Avelino Aguilar

Submitted by:

Itaralde, Ivonne Crystelle S.

PT2-B
 SODIUM THIOPENTAL

Sodium Thiopental also known as Sodium Pentothal (a trademark of Abbott Laboratories, not to be confused
with pentobarbital), thiopental, thiopentone, orTrapanal (also a trademark), is a rapid-onset short-
acting barbiturate general anesthetic that is an analogue of thiobarbital. Sodium thiopental is a core medicine in the
World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic healthcare
system. It was previously the first of three drugs administered during most lethal injections in the United States, but
the U.S. manufacturer Hospira stopped manufacturing the drug and the EU banned the export of the drug for this
purpose.

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. Abbott continued to
make the drug until 2004, when it spun off its hospital-products division as Hospira.

Thiopental is famously associated with a number of anesthetic deaths in victims of the attack on Pearl Harbor. These
deaths, relatively soon after the drug's introduction, were said to be due to excessive doses given to shocked trauma
patients. However, recent evidence available through freedom of information legislation was reviewed in the British
Journal of Anaesthesia, which has suggested that this story was grossly exaggerated. Of the 344 wounded that were
admitted to the Tripler Army Hospital only 13 did not survive and it is unlikely that thiopentone overdose was
responsible for more than a few of these.

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.
CHEMICAL AND PHYSICAL PROPERTIES

4.2 Experimented Properties

4.2.1 Solubility – In water, 96 mg/L at 25 deg C (est)

4.2.2 Vapor Pressure – 2.2X10-10 mm Hg at 25 deg C (est)

4.2.3 LogP – log Kow = 2.85

4.2.4 Decomposition – When heated to decomposition it emits very toxic fumes of nitrogen and sulfur oxides.

4.2.5 Dissociation Constants – pKa = 7..55

USES

Anesthesia - Sodium thiopental is an ultra-short-acting barbiturate and has been used commonly in the induction
phase of general anesthesia. Its use has been largely replaced with that of propofol. 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 sodium 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.

Sodium 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. Sodium 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.
Medically Induced Coma - In addition to anesthesia induction, sodium thiopental was historically used to
induce medical comas. It has now been superseded by drugs such as propofol because their effects wear off more
quickly than thiopental. Patients with brain swelling, causing elevation of intracranial pressure, either secondary to
trauma or following surgery, may benefit from this drug. Sodium thiopental, and the barbiturate class of drugs,
decrease neuronal activity and therefore decrease the production of osmotically active metabolites, which in turn
decreases swelling.

Status epilepticus - In refractory status epilepticus, thiopental may be used to terminate a seizure.

Euthanasia - Sodium thiopental is used intravenously for the purposes of euthanasia. In both Belgium and
the Netherlands, where active euthanasia is allowed by law, the standard protocol recommends sodium thiopental as
the ideal agent to induce coma, followed by pancuronium bromide.

Lethal Injection - Along with pancuronium bromide and potassium chloride, thiopental is used in 34 states of
the U.S. to execute prisoners by lethal injection. A very large dose is given to ensure rapid loss of consciousness.
Although death usually occurs within ten minutes of the beginning of the injection process, some have been known to
take longer. The use of sodium thiopental in execution protocols was challenged in court after a study in the medical
journal The Lancet reported autopsies of executed inmates showed the level of thiopental in their bloodstream was
insufficient to cause unconsciousness.

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 state of Washington is now the second state in the U.S. to use the single-dose sodium thiopental injections for
death penalty executions. On September 10, 2010, Cal Coburn Brown was executed. This was the first execution in
the state to use a single dose, single drug injection. His death was pronounced approximately one and a half minutes
after the intravenous administration of five grams of the drug.
Truth serum - Thiopental (Pentothal) is still used in some places as a truth serum to weaken the resolve of a subject
and make them more compliant to pressure. 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. The drug tends to make subjects loquacious and
cooperative with interrogators; however, the reliability of confessions made under thiopental is questionable. Sodium
thiopental is featured as a truth serum in several Hollywood films, in comics and other literature, and even in popular
music.

Psychiatry - Psychiatrists have used thiopental to desensitize patients with phobias, and to "facilitate the recall of
painful repressed memories." One psychiatrist who worked with thiopental is the Dutch Professor Jan Bastiaans, who
used this procedure to help relieve trauma in surviving victims of the Holocaust.

CONTROVERSIES

Following a shortage that led a court to delay an execution in California, a company spokesman for Hospira, the sole
American manufacturer of the drug, objected to the use of thiopental in lethal injection. "Hospira manufactures this
product because it improves or saves lives, and the company markets it solely for use as indicated on the product
labeling. The drug is not indicated for capital punishment, and Hospira does not support its use in this procedure." On
January 21, 2011, the company announced that it would stop production of sodium thiopental from its plant
in Italy because it could not guarantee Italian authorities that the drug would not be used in executions. Italy was the
only viable place where the company could produce sodium thiopental, leaving the United States without a supplier.
CONTRAINDICATIONS

Thiopental should be used with caution in cases of liver disease, Addison's disease, myxedema, severe heart
disease, severe hypotension, a severe breathing disorder, or a family history of porphyria.

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary edema in rats. This pulmonary
edema was not mediated by cardiac failure or by pulmonary hypertension but was due to increased pulmonary
vascular permeability.

REFERENCES:

https://en.wikipedia.org/wiki/Sodium_thiopental

https://pubchem.ncbi.nlm.nih.gov/compound/thiopental_sodium#section=IUPAC-Name