Thursday, July 28, 2016

A Mystery Writer's Guide to Drugs and Poisons. Part One.

I have a doctorate in Pharmacology--the science behind drugs--and have taught the subject to medical students for twenty years. I have also taught Toxicology, the science of poisons. The two subjects overlap. As any pharmacologist can tell you, every drug can be a toxin, it just depends on the dose.

Drugs and Poisons.

Drugs and/or poisons take their place in mystery literature as murder weapons, as addictive substances related to character flaws or criminal ventures and, in thrillers, as potential terrorist threats which can wipe out whole cities.

On a less dramatic note, characters use drugs for their various ailments and may suffer from their side effects and it is important to get the details right.

Pharmacology and Toxicology are vast subjects with issues related to the thousands of drugs and poisons. In this series I will try to deal with some of the most common situations the mystery writer may encounter. First, however, some basics on how drugs and toxins work.

What Makes Drugs and Toxins Work.

The human body is run by chemicals that it produces. These can be hormones that are released by glands which act elsewhere in the body on organs and tissues or else they can be locally acting substances such as neurotransmitters. What's a neurotransmitter? Nerves, both those that run like wires around the body, and those that comprise the brain, act by releasing stimulants and depressants which affect tissues or act at another nerve. These chemicals are neurotransmitters and run the communication system of the body, giving orders to both the automatic systems that govern functions such as breathing and digestion and the voluntary system that controls movement and willful actions. Neurotransmitters also control the brain functions: consciousness, memory, wakefulness, euphoria, etc.

So, what does a drug do? In most cases* it either acts like the natural chemical or blocks the effect of the natural chemical at its site of action.

Let's have a couple of examples. You are probably familiar with adrenaline (also called epinephrine). It is a chemical released by the body in response to stress or danger. Among other actions, it opens up the lungs for breathing, it makes the heart beat faster, it raises the blood pressure and it directs blood flow to the skeletal muscles. The set of effects from adrenaline are often described as preparing you for "fight or flight."

Adrenaline can be given as a drug. Shock involves a precipitous drop in blood pressure. A doctor may want to raise blood pressure using adrenaline in the case of anaphylactic shock (the type of shock that occurs with a severe allergic reaction such as bee-sting allergies).

Adrenaline was formerly given for asthmatic attacks: it relaxes the bronchiole muscles of the lungs to make breathing easier. In this case, we get to a toxicity: adrenaline not only opens up the bronchioles, it causes the heart to race. It can cause death in those prone to heart attacks. As a general principle of toxicity, some people are more susceptible than others. There are other drugs which can be used for asthma that do not have this effect.

To get back to what I noted above, some drugs mimic while other block the effects of natural compounds. Instead of raising the blood pressure with adrenaline, you might want to lower the blood pressure by providing a drug that blocks the action of circulating adrenaline (and its companion which is released by nerve endings, noradrenaline). Such drugs are often called blockers or inhibitors or else by the more technical term, antagonists.

How Do Drugs Achieve Their Effect?

Drugs, and their natural chemical counterparts, work by binding to receptors which turn on or off cell processes. What is a receptor? The following analogy is over a century old. A drug is the key, the receptor is the lock (or ignition switch). The receptor is typically on the outside of a cell. The drug is carried by blood to the outside of the cells where the drug turns on the cells causing a tissue effect. Why a particular tissue? That's where the receptors are which fit the keys: adrenaline on the heart tissue (and blood vessels and elsewhere where it has its actions).

Let's look at another example. Acetylcholine is a neurotransmitter with many effects throughout the body. Nerves which go to the skin release acetylcholine causing a person to sweat. Nerves which go the salivary glands release acetylcholine causing a person to salivate.

Acetylcholine is also released at the nerves which connect the brain to the skeletal muscles. The skeletal muscles are those that control voluntary movement. Drugs that act like acetylcholine are given to patient with myasthenia gravis. Why? Myasthenia gravis is a disease in which a person's immune system attacks the acetylcholine receptors on the outside of skeletal muscles. The person thereby loses muscle strength. By acting like acetylcholine, a drug can activate some of the remaining receptors.

However, in other circumstances you might want to give a drug that blocks acetylcholine at the skeletal muscles. Why would you want to do that? These drugs (skeletal muscle blockers) are given prior to surgery to prevent the patient from flinching. (General anesthesia does not paralyze the patient, anymore than sleep does not paralyze us.) A good plot device: a murderer substitutes or cuts off the skeletal muscle blocker being infused during a delicate life-or-death surgical procedure.

Let's look at the skeletal muscle blockers from the point of view of poisons. Tubocurarine (Curare) paralyzes the muscles and was discovered by a researcher who noted South American tribes using poison-tipped blow darts to capture animals. It can be fatal in animals or humans because one set of skeletal muscles helps us to breathe. (During surgery, the patient is placed on mechanical ventilation.)

After curare was discovered, but well before it was purified well enough from its plant source to be used as a drug, it made for a popular poison in mystery stories. No one interested in murder cares whether a poison is pure enough to avoid additional toxic effects.

Another set of toxins work through the acetylcholine system. Popular as the villainous weapons in thrillers and popular with villains in real life (Saddam Hussein, the Tokyo attacks), the nerve gases first overload and then knock out the acetylcholine receptors. The effects are several fold. First you have the twitching and spasms from having the skeletal muscles activated. You have the sweat glands and salivary glands turned on. Then you have the skeletal muscles shut down, including those that help you breathe. The nerve gases make for the more terrifying sort of poisons in part because they are active in small concentrations, they can be absorbed by breathing and through the skin (not many toxins can), and they can be spread in a suspended gaseous form. They also make for great plot devices because they have specific antidotes—and not many poisons do.

The Differences Between Drugs and the Natural Body Chemicals.

Although human-made compounds such as adrenaline can be used as drugs, a general rule is that the body exquisitely regulates its own compounds, producing them as needed and then quickly stopping the effect. One of the main ways in which the body stops the action is by breaking down the chemical into ineffective parts (metabolites). Adrenaline has a half-life of about 2 to 3 minutes. Acetylcholine, at the nerve ending, has a half-life of seconds. One major difference between synthesized drugs and the natural compounds is that the synthesized drugs act for a longer time. For example, an asthmatic patient might be taking a drug that acts like adrenaline in the lungs but has a half-life of hours.

So what is half-life? Unless the drug (or toxin) overwhelms the body's system of elimination, the body will eliminate half of the drug dose in a given period of time. A simple illustration is this:

Digoxin (for heart failure or arrhythmias). Half-life: 40 hours.

  • Concentration in blood. (micrograms per milliliter)
  • Zero hour. First measure: 8 ug/mL
  • 40 hours later: 4 ug/mL
  • 40 more hours later: 2 ug/mL
  • 40 more hours later: 1 ug/mL

The drug is disappearing by halves, moving like the traveler on Zeno's bridge.

I provide this table to overcome a misconception. Half-life is not how long a drug acts. It may still be acting the level of 1 ug/mL. -- Or else it may not, it may be at a concentration that is no longer causing an effect. Half-life describes the elimination of the drug. The elimination of its effect is determined by the lower threshold of its effective concentration.

Extending This To Other Drugs.

There are thousands of drugs belonging to hundreds of systems. The differences between them is what receptors they act on, individual toxicities, half-lives, and routes of administration. 

For example, morphine-related drugs act through receptors which are naturally activated by the endorphins. These receptors are located in places which cause pain relief, euphoria, depressed breathing (the main fatal effect with an overdose), and constipation (the common problematic side effect). These receptors are present in other places to provide minor effects such as pinpoint pupils.

Morphine-blockers such as naloxone (Narcan) block the receptors. This won't make much of a difference (they are blocking pain-relief rather than causing pain) unless someone has a dose of morphine-related drugs or endorphins present. In such a case the drug wipes out the euphoria, pain-relief, etc. and restores the breathing.

*A final note on this part. Does every drug either mimic or block the action of a natural human substance? No. One alternative mechanism of action comes with the antibiotics which interfere with the chemistry of microorganisms.

Next. Some Differences Between Drugs and Toxins.

Never Kill A Friend, Ransom Note Press

Never Kill A Friend is available for purchase in hard cover format and as an ebook.
The story follows Shelley Krieg, an African-American detective for the Washington DC Metro PD as she tries to undo a wrong which sent an innocent teenager to prison.

Hard cover: Amazon US
Kindle: Amazon US
Hard cover: Amazon UK
Kindle: Amazon UK
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