Killer Cocktails: The Chemistry Behind the Lethal Injection

In many countries worldwide, including the United States, lethal injection is used as a humane method of executing a death row inmate. With the lethal injection, the life of the inmate can theoretically be cleanly and swiftly ended through administering a number of drugs, with no pain and minimal trauma.

The debate over the lethal injection hit the news again last month when the U.S. Supreme Court ruled against claims that the use of a drug used in lethal injections (midazolam hydrochloride) violates the Eighth Amendment (relating to prohibiting cruel and unusual punishment). Despite this method of capital punishment largely replacing supposedly less humane forms of death such as the electric chair and hanging, there is still great debate over the ethics of certain drugs used, and whether they actually do provide a swift and pain-free death.

But what drugs are involved in this lethal cocktail, and how do these end life in an apparently ethical manner?

The procedure for lethal injection can vary across different countries and even different states. In the United States, execution by lethal injection is typically achieved through the intravenous use of three drugs in succession, each with a different purpose, though in some instances a single-drug method is used, usually involving a lethal dose of anaesthetic.

Sodium Thiopental (Source: Chemspider)

Sodium Thiopental (Source: Chemspider)

But let’s look at the three-part cocktail. The first drug to be administered is usually a barbiturate to act as an anaesthetic (painkiller), used to ensure the remaining steps in the procedure do not cause any pain. Traditionally sodium thiopental is used, a fast-onset but short-acting barbiturate. Barbiturates are compounds which can ultimately produce anaesthetic effects. They act as agonists of gamma-aminobutyric acid (GABA) receptors, which are inhibitory neurotransmitters in the central nervous system. By binding to this receptor, the activity of the central nervous system is depressed, bringing about effects ranging from mild sedation to general anaesthesia. In this instance, a sufficient dosage is administered to render the inmate unconscious, thus ensuring a painless procedure. However some have argued that the fast-acting effects of sodium thiopental can wear off before the execution procedure is complete.

Succinylcholine Chloride (Source: Chemspider)

Succinylcholine Chloride (Source: Chemspider)

Once the inmate is unconscious, a neuromuscular-blocking drug is then administered, generally succinylcholine (also known as suxamethonium chloride) or pancuronium bromide. Compounds such as succinylcholine bind to acetylcholine receptors, blocking the action of acetylcholine, a neurotransmitter essential in the proper functioning of skeletal muscle. When succinylcholine binds to this receptor, a cation channel in the receptor opens and depolarisation of the neuromuscular junction occurs. Normally when acetylcholine binds to this receptor, it soon dissociates following depolarisation and the muscle cell will be ready for the next signal. However compounds such as succinylcholine have a significantly longer duration, ultimately resulting in paralysis. In short, administering a drug such as succinylcholine prevents acetylcholine from communicating with the muscles and thus paralyses the inmate’s muscles, including those used to breathe. Other drugs such as pancuronium bromide can also be used, which have a different mechanism of action but ultimately achieve the same final result of muscle paralysis.

Finally the salt potassium chloride is administered. Within the body a variety of salts are vital for brain function, transmission of nerve signals and the beating of the heart, and these salt levels are tightly regulated by the body. In the normal functioning of the body, the majority of potassium is confined to the cells, with very little being present in the bloodstream at any one time. The introduction of a large amount of potassium chloride disrupts this electrochemical balance as the body’s cell are not able to equilibrate, rendering the cells unable to function, leading to cardiac arrest. In simpler terms, the overdose of potassium chloride brings about a condition known as hyperkalemia, in which the potassium concentration in the body is too high, causing the heart to fail. The inmate is officially declared dead when a cardiac monitor indicates the heart has stopped.

Recently, the drug used to initially render the inmate unconscious, sodium thiopental, has been difficult to obtain for a number of reasons, thus some states in the U.S. have used midazolam hydrochloride, a drug which has ultimately caused a great deal of controversy in recent years, such as in the Clayton Lockett case. This benzodiazepine is commonly used as a sedative, but when used during the lethal injection procedure, it is generally combined with an opiate. This is because midazolam itself has no analgesic (painkilling) effect, thus an additional drug is required to achieve this. Despite its recent use, claims have been made that a number of executions using this drug resulted in the prisoners showing signs of consciousness and gasping, suggesting that they were not quite as unconscious as intended. If the inmate is not unconscious when the muscle paralyser and electrolytes are administered, they may experience suffocation due to the muscle paralysing agent and burning caused by the potassium chloride.

So there we have it – some of the primary drugs administered during the lethal injection procedure and how they react within the body to bring about death. For more information on the death penalty (namely in the U.S), visit the Death Penalty Information Center.

References

Johnson, B. A. 2011. Addiction Medicine: Science and Practice Volume 1. New York: Springer.

Kroll, D. 2014. The Drugs Used in Execution by Lethal Injection. [online] Available from: http://www.forbes.com/sites/davidkroll/2014/05/01/the-pharmacology-and-toxicology-of-execution-by-lethal-injection

Kemsley, J. 2015. Sedative for Lethal Injections Affirmed. [online] Available from: http://cen.acs.org/articles/93/i27/Sedative-Lethal-Injections-Affirmed.html

Cover Image Credit: Thomas Boyd (The Oregonian)

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