Posts tagged: poisons

Bad Chemistry II – Poisons

In the second part of this series I’m going to have a look at some specific types of poisons and the treatments that are available for them. This will not by any means be an exhaustive reference source, but more an overview of substances that tend to feature prominently in fiction, and which tend to fit a particular type of purpose within a narrative.

Cyanide (Fast) – The exact definition of a cyanide is a little confusing, but for the purposes of toxicology it tends to be used to describe organic compounds containing the cyanide group (CN). This chemical group is very common in chemistry, but causes problems for many living creatures when released into solution as an ion, something that happens very easy with organic compounds. This ion inhibits the electron transfer chain with, a key reaction in providing energy for your cells.

Cyanide toxicity is fast, and once it’s present within the bloodstream in large quantities it does pretty much fulfill the Hollywood, drop dead in seconds image, this is most likely to happen when it is breathed in as a gas, or absorbed through the skin.

As such, the treatment of cyanide poisoning is heavily complicated by the fact that the victim is quite probably already dead by the time help arrives (as my Toxicology lecturer put it, somewhat flippantly, if a living patient presents with Hydrogen Cyanide poisoning then congratulations they’re going to live). That said in the case of lower doses, or more slowly absorbed oral poisoning, treatments do exist, mostly involving the introduction of substances into the body that the cyanide will react with. This is a not a magic cure all, but will reduce the severity of the poisoning. Prognosis for survivors is fairly good, but long term damage can result, especially to the heart, brain, and the rest of the nervous system.

Metal Toxicity (Slow) – Metal toxicity is often considered together, not because many heavy metals have the same mechanisms of effect, or even because they target the same tissues within the body, but because the body is very poor at excreting them, meaning that they will tend to concentrate within the body over time, a process known as bio-accumulation. Because of this, treatment often involves using substances, known as chelating agents, which will bind to the metal and help it to be eliminated from the body.

This tendency means that such substances have been often been (mis)used, throughout history, to poison a victim over an extended  period of time, often with the intent of avoiding detection or causing the appearance of a chronic illness. It’s important to remember that their tendency to cause slow long term poisoning does not preclude acute toxicity from occurring from a single large dose, but many of these substances tend to produce fairly general damage to organs, which can make for a long and lingering death even in a large exposure. Neurological damage is very common, especially with lead and mercury.

Another key issue with metal toxicity, is the form that they are present in. Elemental metals tend to be poorly absorbed by the body and relatively non-toxic, but when incorporated into organic compounds they can become many times more bio-available, and hence toxic. Elemental iron is sufficiently non-toxic that children’s cereal is pretty much “fortified” by mixing in iron filings, organic iron is highly toxic, which is the reason that the first thing a doctor would establish if your child had overdosed on vitamins, is whether they contain iron or not. Mercury also presents the risk that it will evaporate which makes it much more readily absorbed by the body.

Intentional heavy metal poisoning is now rare, at least in the developed world, primarily because it is very easy to detect, but environmental toxicity is still a very big deal, especially in poorer countries, often linked to us of the substances in industry, or their recovery from used electronics. Toxicity may also result due to illegal or inappropriate incorporation of the metal into another product, often as a dye.

Anticoagulants (Messy) – This usually means the classic rat poison warfarin, although there are a number of similar drugs, and aspirin can produce the same effects. In toxic concentrations these kill via blood loss, primarily resulting from internal bleeding.  Many anticoagulants merely block coagulant production, something that takes an extended period of time and which can be treated by replacing factor precursors and giving a blood transfusion, making it a relatively slow and unpleasant form of poisoning, but one that would be fairly easy to diagnose and treat where medical help is available.

Botulinum Toxin (Potent) – The most potent toxin that I’m aware of is Botulinum toxin which is produced by the bacteria Clostridum Botulinum. This substance causes the food poisoning known as botulism, and is used under the name Botox in a variety of cosmetic medical procedures, as well as some other medical applications. The toxin as released by the bacteria contains a number of very similar substances which prevent the release of neurotransmitters from nerve junctions. Depending on administration route the lethal dose for a human may be less than 0.1 micrograms (or one ten millionth of a gram).

The substance represents an obvious candidate for use in warfare or terrorism. Whilst it is not particularly well suited to use as a weapon in terms of stability or absorption, its incredible potency and relatively straightforward manufacturing process make it a very real threat.

Tetrodotoxin (exotic) – Tetrodotoxin is of interest, primarily because it occurs in a wide range of different creatures, many of which have been used prominently in fiction. Tetrodotoxin is responsible for the toxicity of Japanese pufferfish fugu, the bite of the blue ringed octopus, as well as wide and varied range of toads, sea stars, fish and worms. This is thought to be possible because the toxin is actually manufactured by one of a number of different bacteria, that are living within the creatures.

The toxin acts on the nervous system and serves to paralyze skeletal muscles, usually leading to death as a result of suffocation. The victim can remain perfectly lucid but paralysed until they expire. Whilst its true that the toxin has no antidote, this does not mean that it can not be treated. Treatment primarily consists of supporting the patients breathing mechanically and trying to prevent any further absorption of the drug, although serious cardiac symptoms can also occur as the patient loses the ability to regulate their heart rate. If the patient can be kept alive by supporting respiration for at least 24 hours the effects of the drug will start to wear of, and the patient has an excellent chance of a full recovery.

Bad chemistry I – Poisoning

A writer’s guide to poison, poisoning, and poisonous things

This article is going to provide a brief overview of toxicology, highlighting the concepts and considerations that I believe will be most useful to writers.

This will be a series of articles, the next will discuss individual poisons in more detail, with others talking about types of chemical hazards as well as radiation.

I’m therefore not going to spend much time listing exotic poisons or talking about individual substances in this article, although I will be giving examples where relevant.

 

Confusing words-

These are the words with the important definitions.

Poison – This refers to any substance that interacts with the functioning of a biological organism in a negative way.  It’s the umbrella term. As this definition could actually encompass just about every known substance, the term tends to be used only to describe substances in the specific context that harm is likely to occur, or substances that are particularly prone to negative interactions with biology.

Toxin –  Toxins are poisons that are produced by a biological organism. Toxins are poisons, but not all poisons are toxins. This is not helped by the way that most words that derive from the same Greek root, such as toxicology, toxic, or intoxication, are all general terms.

Venom – The next step down, a venom refers specifically to a toxin that is injected directly into another organism, whether by sting, fang or claw.

So, arsenic introduced into food is a poison, but not a toxin or a venom. Ricin, which is derived from the caster oil plant, is a toxin, but not a venom. If you are bitten by a snake, then the venom that it injects, is also a toxin and a poison. All three substances are toxic.

There are grey areas here, but in practical terms you just need to consider the origin of the substance at hand. If it came from an animal or plant, you can call it a toxin, if it was injected by that creature, it’s also a venom. If neither of those apply, you should just call it a poison.

So, what makes a substance poisonous?

 

Mechanism –

There a lot of different ways that a poison can interfere with biology, this can involve a relatively crude chemical reaction, such as the corrosive destruction of tissue, an overloading of normal biological processes, or very specific and complicated interactions with biochemistry.

In general, the biologically derived toxins tend to be large complicated molecules, often proteins, which have complex interaction with biological processes. Venoms, especially, are often composed of multiple discrete substances, often with separate modes of action.

The more complex the molecule and interaction, the more likely it is that the poison will be specific to a given organism, tissue, or situation. As I’ve discussed at length in an earlier article, complex interaction between unrelated biochemical systems is unlikely, something which may become a problem when writing “hard” science fiction.

 

Dosage-

Probably the most important concept in toxicology, famously stated by Paracelsus, who is considered the father of modern Toxicology –

“All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.”

In large enough amounts even water can be toxic, and I’m not talking about drowning here.

In the abstract, any living organism can be considered as a very complicated series of chemical reactions, and so, if you throw enough of any other chemical at them, eventually bad things will tend to happen.

Conversely, many substances which are widely recognized as poisons are present in small amounts all around us. Chances are that you have accidentally consumed an apple pip at some point in your life, without immediately expiring as a result of the tiny quantities of cyanide that it contained.

It is dosage then that is most often used when comparing the toxicity of substances. You may have seen this expressed as LD50 values, a rather grim notation in which the figure indicates a quantity of a given substance required to kill half the organisms exposed to it.

LD50 values must be approached cautiously for a number of reasons. Firstly, for reasons that should be obvious, human toxicology data is seldom acquired by careful and systematic experimentation, rather from anecdote and reconstruction of tragic events, contributed by people who were often too busy at the time to take careful measurements. Human data is often missing altogether for many substances, and estimates can only be made by extrapolating data from other organisms.

Beyond that there is still room for confusion. LD50 values should specify weight and administration, but this information is often omitted in favor of lowest possible LD50 value. Consider that a 6’3” male can readily weigh 50% more than a 5’2” women and more than three times as much as a 5 year old child. For some substances the dosage will not scale well with mass anyway. Children or the elderly or those in poor health, or with specific conditions, may be more susceptible, and, as will be discussed, genetics and behavior often play important roles as well.

 

Administration route-

It’s not uncommon to hear journalists describe any large, allegedly newsworthy, accumulation of toxic substances according to the number of people that could potentially be poisoned, as in “enough botulinum toxin, to kill 1000 elephants”. This is a lot like describing the contents of a knife shop by trying to estimate the number of people that could be stabbed. Poisons do not magically distribute themselves amongst and within the population that they may be intended to poison.

Some substances are readily absorbed through the lungs, or directly through the skin, but others must be ingested or even injected directly, something that is less likely to happen by accident.

Even after the poison enters the body, it still has to reach the susceptible target tissue. It’s quite possible for an injected poison to become trapped in muscle tissue rather than reaching the bloodstream. The brain is protected from many toxic substances by a system of filtration, termed the blood-brain barrier. Certain diseases can reduce the effectiveness of this barrier, which will render the sufferer susceptible to those toxins.

If a poison is in the form of a gas, or absorbed through skin contact, it is likely that many times the lethal dose will be needed to ensure that enough is taken up by the target.

 

Metabolism-

What happens to the poison after it enters the body is also important. The body is effective at removing molecules that shouldn’t be present, or which no longer serve a purpose. This is a progressive, but surprisingly predictable process, where the offending molecules are cut up into progressively smaller metabolites by metabolic enzymes and then excreted.

For toxic substances this often means neutralization, but other substances that weren’t initially harmful may actually be transformed into a toxic form.

An important concept here, that you might come across when researching this subject, is that of first pass metabolism, which describes the way that drugs absorbed in the stomach, will pass immediately through the liver, where a lot of metabolic processes take place. This means that even some substances that are absorbed well by the stomach will be dramatically influenced by injecting them directly. It also means that the precise site at which an injection of toxic substances occurs, both relative to the target tissue and relative to the liver can be important.

These metabolic pathways are often shared, and can potentially be overloaded. The reason that alcohol is contraindicated when taking many types of medication is that it shares a common metabolic pathway with them. Other substances can directly inhibit metabolic enzymes; this is true of chemicals contained within Grapefruit of all things, the fruit of nightmares, if you are a pharmacologist.

This can all have interesting implications. In the case of ethylene-glycol (anti-freeze) poisoning, the toxicity results from metabolism by the alcohol metabolizing pathway. Because the pathway has a much higher affinity for the alcohol, the poisoning can be treated by giving the victim large quantities of ethanol until all the antifreeze has been excreted, essentially, treatment involves getting as drunk as possible.

Metabolic pathways can be up-regulated or down-regulated by the body over time, in response to prolonged exposure to the offending metabolite. This is the mechanism by which people build up resistance to poisons, medication, or drugs of abuse, which will, in turn, influence their susceptibility to other drugs or poisons metabolized in the same way. Metabolism can also vary as a result of genetic factors, especially across different ethnicities. The enzyme complicit in paracetamol’s (acetaminophen) toxicity, for example, has been observed to vary by a factor of as much as 50 between individuals, and will increase with chronic alcohol exposure, increasing the risk of poisoning.

 

Elimination-

Some substances are metabolized or are excreted from the body almost immediately, but others persist for a very long time. This means that repeated exposure to relatively small amounts of that substance over a long period of time can result in poisoning. This is particularly common with heavy metal toxicity.

Aside from normal metabolic processes, the toxicity of substance is also influenced by what happens to individual molecules whilst exerting their harmful effect. A poison that is consumed in that reaction is usually going to be less problematic than one which can as a catalyst for other reactions, as this means that the molecule itself will persist and continue to produce harm. Some enzyme molecules are individually capable of catalyzing more than a million reactions per second without being used up.

Also important is the fate of whatever substances that the toxin is reacting with. Some toxins are eliminated quickly, but irreversibly destroy the target molecules or tissue, and the body’s ability to quickly replace these substances or repair the damage is limited. Nerve agents, for example, work by binding to an enzyme anticholinesterase involved in nerve transmission, often producing permanent bonds with the molecule, which would otherwise be taken back up and recycled by the body, resulting in prolonged poisoning. One of the drugs used to treat poisoning of this type, Pralidoxime Chloride acts to reactivate the enzyme and restore normal function.

Speaking of which…

 

Antidotes and other treatments-

Almost as important to fiction as the poison, is the concept of the antidote, the magical wonder drug that will infallibly reverse poisoning in seconds, if administered at any point before death (the time of which can be estimated to the second).

Needless to say, it’s not quite that simple in reality.

It’s important to realize that, whilst many types of poisoning can be treated with a specific drug, these treatments are not often fast, infallible, or even safe. Some substances oppose the effect of poison by producing an opposing effect, in essence poisoning the patient in the opposite direction, others do nothing to repair harm, but facilitate the breakdown or excretion of the poison, prevent it from binding to its target, or even just compete to produce the same mischief in a more reversible way.

Because animal toxins toxin molecules are often composed of large and complex molecules, antibodies produced by the immune system are sometimes effective against them, allowing an immune response to the toxin to develop. This is exploited in order to manufacture antiserum, extracted from animals deliberately exposed to the toxin. However, these treatments can produce a severe immune response from the patient themselves, especially on repeated exposure, and are sufficiently risky that, in reality, not introducing the antiserum to the patient is often judged the lesser risk.

More apparently cinematic antidotes do exist, but even then there can be unexpected problems, Opioid poisoning can be spectacularly reversed in seconds, by injection of the drug naloxone (which also produces the instant onset of withdrawal symptoms if the poisoning was caused by abuse), but the effects of the antidote are of shorter duration than the underlying poisoning, meaning that unless the patient is given subsequent doses, they will relapse when it wears off. Preventing a spectacularly withdrawn drug addict from leaving the emergency room in search of another fix, after being apparently cured of their overdose can be a real problem for a doctor.

When writing dialogue it’s probably sensible to avoid having a doctor or biologist use the term antidote at all, they may use it in individual cases, especially when talking to patients, but in general they are more likely to think and talk about these substances in terms of “medication” or “treatment”.

Just as important to the real world treatment of poisoning is the physical reduction of poison absorption. If the poison has been taken in by mouth this means inducing vomiting (when safe to do so), pumping out the stomach, or introducing activated charcoal into the stomach, which will neutralize a lot of substances before they can be absorbed.

If the substance is absorbed through the skin, the victim can be washed (often with a mild bleach solution). If the poison has been injected it is sometime appropriate to attempt to recover the poison by suction or use a tourniquet to prevent its spread into general circulation.

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