A is for Arsenic (41 page)

The dampening effect barbiturate drugs have on the nervous system means they also have applications in other areas. In 1911 a German doctor, Alfred Hauptmann (1881–1948), was living and working in a hospital that had a ward of epileptic patients. The noises made when the patients were suffering seizures kept Hauptmann awake at night. In a desperate attempt to get some rest he decided to sedate the epileptics with phenobarbitone. The drug succeeded in sedating them, and it
also reduced their fits, with this benefit continuing even after the sedative effects had worn off. Phenobarbitone is still used as an anticonvulsant drug in the treatment of epilepsy today.

Other barbiturates included Pentothal, which found notoriety as a ‘truth drug'.
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It is thought that lying is a more complex procedure than truth-telling; so, in theory, by using a drug that depresses the function of nerves in the cortex of the brain, people are more likely to tell the truth. Pentothal is also a good example of the potentially lethal nature of barbiturates; it has been used in the United States in lethal injections of criminals, as have other barbiturate drugs, the idea being that large doses of these compounds induce a deep coma, allowing the administration of other lethal compounds that stop the heart.

When barbiturates were first released onto the market there was thought to be a safe margin between a therapeutic dose and a lethal one. However, the 12-fold increase in suicides by barbiturates between 1938 and 1954 told a different story. Veronal was prescribed in therapeutic doses of between five and fifteen grains (0.3–1.0g), but a lethal dose was only around sixty grains (around 4g). In the 1912 edition of
The Art of Dispensing
that Dame Agatha studied for her dispensing exams, a dose of seven and a half grains (about 0.5g) of Veronal for men and five grains (about 0.3g) for women is recommended. The gap between therapeutic and lethal doses could be considerably narrowed because, over prolonged use, individuals can develop a tolerance to the drug, and they go on to require larger doses to achieve the same sedative effect. These drugs are also potentially addictive in a similar way to alcohol, opening them up to abuse. Also, owing to the fact that barbiturates slow reactions and increase drowsiness, many sleepy individuals took an extra (lethal) dose without realising what they were doing.

In 1948, worldwide production of barbiturates was more than 300 tons per annum, but in the 1950s the dangers had begun to be better understood, as an increasing number of people became addicted and some died as a result of overdose. The next decade saw barbiturates largely replaced by benzodiazepines, which produce much the same effects (and may also be addictive) but are far less likely to lead to accidental overdose. One of the few remaining medical applications for barbiturates is in surgery; rapid-acting barbiturates that yield short periods of sedation are administered before an operation to induce unconsciousness.

How barbiturates kill

All barbiturates exhibit a similar spectrum of pharmacological effects, but they differ with respect to the time they either kick in or last for. Their effects are due to interactions with the nervous system that make it more difficult for nerve cells to be activated, resulting in an overall depression of nerve activity.

Barbiturates activate specific sites called gamma-aminobutyric acid (or GABA) receptors in the nerve cells. GABA is one of the many neurotransmitters, or molecules used as chemical messengers between nerves. GABA has other functions within the body, including maintaining muscle tone, but its principal role is to inhibit nerve activation.

Barbiturates mainly interact with GABA
receptors in nerve cells in the brain. Each GABA receptor is formed of five subunits around a central pore that allows chloride ions (Cl
−
) to flow into the nerve cell. There are 15 different potential subunits; each of the five making up a receptor can be different. Therefore, there is huge variety in the composition of GABA receptors; this helps enable the diversity and complexity necessary for the operation of an intricate and sophisticated organ such as the brain.

As we have seen, signals are generated by the movement of potassium ions in and sodium ions out of nerve cells (see page
here
). The movement of these ions produces a tiny electric current that is transmitted along the length of the nerve,
triggering the release of neurotransmitters at its end to pass on the signal to an adjoining nerve or muscle cell. When at rest, nerve cells are slightly negatively charged on the inside. When the nerve ‘fires', the movement of ions means the internal charge goes from negative to zero, and then – for just a few milliseconds – becomes slightly positive. Molecular pumps then move the ions back to their original positions, restoring the negative charge inside the nerve cell and making it ready to fire again. Barbiturate interactions with the cell encourage more negative charge to accumulate inside when it is at rest, making it more difficult for the nerve to fire. In this way, nervous function is depressed.

GABA receptors also interact with alcohol; when taken with barbiturates, the two enhance each other's effects, leading to a greater sedation than the sum of the parts might suggest. Benzodiazepines also bind to GABA receptors. The binding of one of these molecules increases the binding of another and taking combinations of these drugs can therefore be very dangerous.

By suppressing the activity of the central nervous system, barbiturates can cause drowsiness and slowed reactions. This has been described as like being drunk, especially if there is a delay after taking the drug before going to sleep. The end result is an unconscious state that resembles sleep. There are three distinct stages of sleep; humans normally go through all of them over the course of the night, spending around 20 per cent of their sleeping time in ‘deep' sleep, 20 per cent in ‘dream' sleep and 60 per cent in ‘light' sleep. Barbiturates change the sleep pattern, resulting in less dream and deep sleep but more light sleep (approximately 80 per cent). People taking sleeping drugs often report that they do not feel as rested after drug-induced sleep as they do after normal sleep. They may find it difficult to wake up, and remain groggy the following morning. In the case of barbiturates this is sometimes described as a ‘hangover'.

When people stop taking sleeping drugs their sleep is often disrupted further as the sleep pattern changes again. After the
drug is withdrawn they experience a large increase in the time spent in dream sleep (to 40 per cent) and a decrease in deep sleep (to 10 per cent). Nightmares and vivid dreams are a common consequence. After a sudden withdrawal from barbiturates, especially following prolonged use, the symptoms are more serious and can even kill. Individuals can experience extreme anxiety, convulsions and hallucinations, particularly if they have been a heavy user of the drug. Other symptoms may include nausea and vomiting, and in extreme cases delirium, fever and coma.

When an overdose of barbiturates is taken, the activity of the central nervous system is depressed to the point that breathing may stop. However, there are other effects that can contribute to or cause death. Barbiturates cause fluids to build up in the muscles, lungs and brain, causing oedema and pneumonia. Slower breathing rates lead to higher levels of carbon dioxide in the body, as this cannot be expelled so effectively from the lungs. Carbon dioxide in the blood forms carbonic acid, increasing its acidity. There may also be a lack of oxygen being taken into the body, and cyanosis – a blue coloration of the skin – may be seen. Due to suppression of the ‘cough' reflex, it will be difficult to clear fluid from the lungs and throat; this can be especially dangerous if the barbiturates cause the individual to vomit.

Barbiturates also interact with enzymes in the liver that are involved in metabolising drugs, including the barbiturates themselves. Prolonged use of barbiturates results in the faster metabolism of the drug into inactive forms (which are excreted from the body). The result of this is the development of tolerance. Ever-increasing doses of barbiturates are needed to keep pace with the breakdown in the liver while still having enough left to act on the nerves. This also means that barbiturates are dangerous when taken with other medication, as the increased rate of metabolism results in other drugs having less effect on the body. Barbiturates are dangerous drugs; the combined effects of a build-up of tolerance and their sedative effects make a patient mentally sluggish, at which point they are
more likely to accidentally overdose. This appears to be the case with Carlotta Adams in
Lord Edgware Dies
.

Is there an antidote?

There is no specific antidote for barbiturate overdose, but with supportive care more than 95 per cent of patients would be expected to make a full recovery. In severe overdoses it may take up to five days for the patient to regain consciousness, but by supporting their breathing, ensuring that they are receiving enough oxygen and that carbon dioxide is being expelled from the lungs, as well as clearing their lungs of mucus, they are unlikely to die.

Some real-life cases

There have been many famous victims of barbiturate overdose: Judy Garland and Jimi Hendrix, for example. These deaths have generally been attributed to accident or suicide. One of the most famous victims of a barbiturate overdose was Marilyn Monroe. At Monroe's autopsy the pathologist found enough Nembutal (pentobarbital) and chloral hydrate in her body to kill ten people, but debate still rages as to how it got there.

The first known case of murder using barbiturates occurred in 1955, long after Agatha Christie wrote
Lord Edgware Dies
. She can hardly be blamed for inspiring this particularly cold-hearted murder, as the lethal properties of barbiturates were well known by the 1950s, owing to the number of suicide victims using these drugs.

At 1.30 p.m. on 21 July 1955, John Armstrong called Dr Bernard Johnson, saying his five-month-old baby son Terence was ill. Dr Johnson's colleague, Dr Buchanan, had received a similar call the previous evening, but Armstrong had not seemed overly worried, so Buchanan waited until 9 a.m. the following morning before calling round to find the baby happy and well. Armstrong had two other children with his wife Janet and the couple, residents of Gosport in Hampshire, were feeling the financial strain of supporting the family. They had also suffered a tragedy when their first son, Stephen, had died
the previous year. Their daughter Pamela had also suffered an illness serious enough to need a stay in hospital. The cause of the illness was not known at the time, but Pamela made a full recovery and returned home.

A second call to the doctor on 22 July sounded more urgent, and Dr Johnson went directly to the house, where he found the baby dead. Initially he did not suspect foul play but the parents' apparent lack of grief was troubling,
¹⁰²
and in any case he could not determine the cause of death. A post-mortem was ordered, as would be the case for any sudden death of a child today. Dr Johnson also took the precaution of taking possession of the baby's bottle, and a pillow that Terence had vomited on to the previous night.

The post-mortem examination revealed no obvious cause of death, but a shrivelled red shell was found in the larynx of the baby, and more red shells lay among the stomach contents. The pathologist thought the shells looked like the skins of daphne berries, which are highly toxic, and a fruiting daphne tree was growing in the Armstrongs' garden. Terence had been in his pram under the tree the day before his death.

The pathologist carefully placed the red shells from the larynx in a bottle of formaldehyde and stored it in a refrigerator, along with another bottle containing the stomach contents of the child, for further examination at a later date. The next day the pathologist took a look at the bottles and found that the red shells had disappeared, leaving the liquid contents stained red.

Chemical analysis of the liquids revealed the presence of corn starch and eosin, a red dye, but no signs of daphne berries or their toxic components, or any other poison, for that matter. The cause of the infant's death remained a mystery, and it would have stayed that way if it hadn't been for the bad impression Armstrong had made on the investigating officer.
The detective made further enquiries in Armstrong's workplace, and went back to see the pathologist.

In the intervening period the pathologist had mulled over the question of the disappearing shells. The colour of the shells reminded him of the gelatin capsules used to contain the drug Seconal.
¹⁰³
Seconal was freely prescribed in the 1950s. It was first released on to the market in 1934, and by the 1960s it was widely abused; the red capsules were commonly known as ‘seccies', ‘red devils' or ‘red hearts'. Seconal is still manufactured today; it is prescribed in 100mg tablets for the treatment of epilepsy, as a temporary treatment for insomnia, and pre-operatively in short surgical procedures. But John Armstrong had no need of a prescription, as he was a nurse at the local hospital and could help himself. Enquiries at the hospital revealed that several boxes of Seconal had disappeared recently.

The pathologist obtained some capsules and showed that they dissolved in gastric juices, producing the same red colour as in the dissolved shells from the baby's body; Seconal, though never previously used in a murder, would be expected to kill a baby in very small quantities. By this stage the scientific expertise of Scotland Yard had been called in. Seconal, once extracted from the vomit on the baby's pillow, could be identified by its unique melting point (among the barbiturates) of 95°C.

With circumstantial evidence against John Armstrong mounting, an investigation was opened into the death of his eldest son Stephen and Pamela's illness the previous year. The symptoms all the children had displayed were remarkably similar, with difficulty breathing, discoloration to the face and drowsiness. Stephen's body was exhumed but it was found to be too decomposed to determine whether Seconal was present or not; however, the police and pathologists were convinced that both he and baby Terence had been killed with barbiturates. The only thing that could not be proved was that the
Armstrongs had been in possession of Seconal on the day the baby died. Evidence of this came a year later, and in a rather unusual manner.