Wednesday, August 17, 2016

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

Poisons Versus Drugs.

"All happy families are alike. Each unhappy family is unhappy in its own way." Leo Tolstoy.

In order to achieve a therapeutic effect without toxicity, a drug has to work perfectly: not too much effect, not too little. It has to be directed to the cause of the ailment and not act elsewhere. It is hard to get things right.

In contrast, there are many ways to get things wrong.

The Mechanisms by Which Toxins Work.

These are the major ways in which toxins achieve their actions.

  • For a drug having a poisoning effect, that effect is an extension of the beneficial effect.
For example, a high blood pressure medicine lowers the blood pressure by too much. A stimulant overstimulates. This can also happen indirectly. As a drug concentration goes up, even an otherwise safe drug begins to activate or deactivate other physiological processes.

  • The poison interferes with essential physiological processes.
It prevents red blood cells from carrying oxygen. (Cyanide).
It interferes with cells using oxygen (Arsenic.)
It disrupts the automatic beat of the heart. (Digoxin in higher doses, oleander, which works through the same mechanism as digoxin).
It disrupts nerve transmission (Curare and some snake poisons. Botulinum. Similarly black widow venom overloads nerve transmission).

  • The poison is caustic. 
It will damage or kill the exposed tissue. (Many snake venoms, often by constricting blood vessels and cutting off blood supply. Tissue death can lead to gangrene.)

  • The compound is made toxic by the body.
Acetaminophen (brand name: Tylenol) is one of the main culprits in drug overdose. The liver transforms it into a toxic compound which, in high concentrations, can destroy the liver.

  • The poison causes DNA damage. 
This can result in a very delayed response (as in years or decades) of causing cancer.

  • There are drug-drug or drug-toxin interactions. 
There are two main ways by which one drug plus a second chemical can be toxic or fatal.

The first is through their mechanism of action: you add together two chemicals that work hand in hand to increase an effect. A well-known example is barbiturates plus alcohol. Both are CNS depressants: that is, they lower consciousness. Together they can put a victim into a stupor, a coma, or death. Sometimes drugs from different categories have overlapping mechanisms. Many drugs used for migraine headaches act through the neurotransmitter serotonin. Many antidepressants also increase serotonin. Sero (blood) tonin (tone, tension), when it is bumped up in concentration, can cause a spike in blood pressure which can be fatal.

The second major mechanism of toxic interactions is when drug A interferes with the elimination of drug B. In this case the concentration of drug B accumulates in blood to toxic levels.

  • Allergies. 

Every drug will have someone allergic to it. Most allergies are not severe. Some drugs (such as penicillin) can trigger potentially fatal reactions in those who are sensitized.

Oleander - a favorite among mystery authors

Things that Authors Get Wrong About Poisons.

1. Death is not instantaneous.

Fast-acting toxins like cyanide or curare are somewhat similar to the victim drowning. In this case, oxygen is cut off. The victim will die over time. Imagine holding your breath until you pass out (three minutes?). Add on to this an additional time in which the irreparable brain damage takes place. Another two to three minutes.

Cyanide was used for gas chamber execution and the victims typically took several minutes before becoming unconscious. Similarly, if the heart stops beating, a patient will continue to live for several minutes. If you want a character to be poisoned and not be able to complete the sentence, "The murderer is. . . ," then you probably need to give a compound that will cause unconsciousness (which can be rapid, several seconds) before death, which will take minutes. 

2. Death is often not certain.

This is a pet peeve of mine. A murderer pushes the victim down the stairs, certain the victim will die. Such an act may cause death, but chances are the victim will come out bruised. Similarly, with poisons, except in cases of overkill (very high doses), death is not assured. Some people (Rasputin) will survive the attempt. Along these lines:

3. The measures of lethality are not exact.

You will find terms related to drug toxicity like "therapeutic index." Therapeutic index is the ratio of the dose that causes lethality in fifty per cent of the population (lethal dose 50, LD50) divided by the dose that provides a positive effect in fifty per cent of the population (effective dose 50). If it takes ten times as much drug to kill fifty percent of people than it does to treat 50 per cent, then the therapeutic index is 10.

To illustrate the uncertainties of the therapeutic index and show how the concept is misused, I provide my students with the following example from the book "Who Killed Kurt Cobain?" Ian Halperin, Max Wallace, 1999, Carroll Publishing Group.

The background: Kurt Cobain, lead singer of the music group Nirvana, died on April 8, 1994. He had a high dose of heroin in his blood and a shotgun wound to his head. His death was ruled a suicide. In "Who Killed Kurt Cobain?" the authors stated it could only be murder. Cobain's blood contained 1.52 ug/mL heroin/morphine. The LD50 is 0.5 ug/mL.

The authors said, "This level [1.52 ug/mL] is widely known to represent three times the lethal dose of heroin. . ." and "a blood morphine level of 0.5ug/mL is . . . the established maximum lethal dose, even for severe addicts." The authors argue that the high dose of heroin would have been nearly instantly fatal or incapacitating and would not have permitted Cobain time to employ a shotgun to kill himself.

What’s wrong with this argument? Well, several things.

  a. What the hell is "maximum lethal dose?" You double the maximum lethal dose and you still have a lethal dose.

  b. LD50 says nothing about "instantly fatal or incapacitating" and it wouldn't have been. Fatality through heroin overdose is through suppression of breathing which does not cause instantaneous death. A high dose of heroin may have had Cobain fall asleep in a few seconds.

  c. LD50 says nothing about "even for severe addicts." Severe addicts tend to have tolerance to drug effects.

  d. There is no guarantee that three times LD50 is going to kill 90% of subjects, much less 100%. That's not how the calculations work.

  e. Lethal dose calculations come from animal experiments (they don't run lethality experiments in humans) and the findings may not directly extrapolate.

4. Analyses for Toxins Tend to Look for the Usual Suspects.

Unless the drug or toxin to be found is mentioned in advance, the typical post-mortem forensic analysis is going to miss compounds that are active in small concentrations. It will find toxins that are present at high concentrations and will screen for the most likely poisons.

You can find traces of a poison in blood or in hair using ultra-sensitive techniques: particularly if you know what to look for. Translating this to another use: yes, an ultra-sensitive drug test could find trace THC levels from the marijuana joint you smoked two weeks but that's not the test that people usually run.

5. Getting the Poison There is as Important as Choosing a Poison that Works.

Typically, for a poison to be fatal, it has to achieve a lethal concentration in blood. In other words, it has to get into your system. This detail is overlooked in a lot of thriller/international terrorism poison-the-masses novels. The author imagines that by poisoning a water supply, you will be able to kill off a city.

This scenario doesn't work. First, you go to the city reservoir. Then you have to have enough poison to pour in that would make each glassful lethal. Then, the toxin had better be equally suspended throughout the water volume: it had better not be oily and rise to the surface or else precipitate or else bind to minerals. And it had better be odorless and tasteless. And, if it gets to the person who drinks tap water, it had better not break down in stomach acid or digestive juices.

With gases, there is a huge amount of air in which the compound can dilute. The historical lethal attacks with gas are usually limited to small or enclosed areas. Not a good thing, but not wiping out whole cities.

5a. Getting the Poison Inside the Victim.

On an individual level, the compound must get into the bloodstream. Not many compounds are absorbed through the skin and therefore there are only a few drugs and toxins that could be delivered by skin contact.

The oral route is more likely to be effective. The GI tract is made for absorbing chemicals: nutrients. This absorptive process makes it good for absorbing many, although not all, types of toxins. Large molecules can't be absorbed through the GI tract and if a compound is a protein (as many toxins are), it will be broken down by digestive juices and absorbed as nutrition.

The lung is good for absorbing, but the drug has to be a gas, vaporized (smoke) or else suspended in droplets (spray).  Not much of what you breathe in gets into the blood, but for a toxin that is active in small amounts, that may be enough. The mustard gases (famous from World War I) did not need to get into the blood. They chemically attacked the tissues where they made contact, including the eyes, the throat and the airways.

If you want to be sure a poison gets into the blood, injection is the surest bet. Whether it is subcutaneous (making a blister), IV drip, blow dart, or a full bolus injected into the veins, most any compound, including those that won't be absorbed anywhere else will get into the blood system.

End Note.

With such a large subject to cover this pair of posts may have been too general / or the examples too limited. If someone has a particular question about a toxin feel free to write me.

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
Barnes and Noble 


Post a Comment