Antidotes for Poison

Most people have probably watched a movie or TV show where the protagonist had to find an antidote to a mysterious poison before it’s too late. In reality, it takes more than a simple ingredient or a quick fix. There are two main variables that determine how to treat a poisoning: the dose of the poison, and the duration of exposure to the toxin. In fact, an antidote is a larger term for an agent that counteracts a poison or toxic element in various ways. These methods usually include direct action on the toxin, action on the toxin binding site, decreasing toxic metabolites, and counteracting the effects of the poison (Chacko, B., & Peter, J. V. 2019).

Direct action to counteract a poison can be done in a variety of methods. An example of these methods is activated charcoal, a highly porous version of charcoal. Activated charcoal works because it consists of a process in which it adsorbs noxious substances onto its surfaces to prevent them from being absorbed into the gastrointestinal tract (Chacko, B., & Peter, J. V. 2019). Many factors contribute to how effective this charcoal adsorption will be, such as the particle of the poison itself and outlying factors in the stomach. Activated charcoal is very effective, absorbing toxins from amphetamines to nicotine, although there is a risk, because too much can be harmful to the body. While a very good option,  charcoal fails as an antidote for cyanides, metals like lithium, and other anorganic salts such as sodium chloride (Zellner, et al. 2019). 

Chelation antidotes are another type of antidotes that utilize the principle of chelation. In chemistry, chelation is a type of chemical bond formed between ions. These agents bind to heavy metals like mercury or lead and form stable complexes (a type of compound) that can then exit the body (Chacko, B., & Peter, J. V. 2019). Chemical antidotes are used to treat metal poisoning, like mercury, lead, arsenic, iron, or even uranium poisoning. With uranium poisoning, specifically inhaled uranium, doses can be delivered up to 6 hours after exposure, and consist of 10-40 times the amount of toxic substance (Li, et al. 2024).

Action on the binding site can be done through receptor or enzyme antagonism, a process in which a substance connects to a receptor and blocks it, rather than letting it activate and cause a reaction, like a substance called an agonist. This blocks the effects of the poison, and is effective for conditions like opioid overdose, where the drug Naloxone is used. When looking at the enzyme itself, the action can be one of two options: competitive inhibition or a newer tactic, reactivation of enzyme activity. In competitive inhibition, doctors use substances like ethyl alcohol, which tries to bind to alcohol dehydrogenase (an enzyme that metabolizes alcohol) instead of other, harmful substances, which then limits the formation of noxious metabolites. The other process, reactivation of activity is done by using oximes to reactivate enzymes (Chacko, B., & Peter, J. V. 2019). As this is a newer technique, results vary, but it seems to be most effective against nerve poisoning (Eddleston, et al. 2002).

Another type of antidote is one that decreases toxic metabolites. A metabolite in this case is a substance formed in metabolism. Toxic metabolites are metabolites that form as “intermediates, side products, or end products of metabolism” and are toxic to the body (Lilja E., et al. 2017). This type of antidote is used in cases of paracetamol overdose, and sometimes liver failure due to acetaminophen overdose (Ershad M., et al. 2019). In this case, an antidote known as N-Acetylcysteine (NAC), works against the paracetamol, which depletes reserves of an important peptide known as glutathione, by refilling glutathione reserves, and “binding to toxic metabolites and scavenging free radicals” (Ershad M., et al. 2019). NAC can be ingested through a variety of methods including pills, powders, and solutions to inhale. A similar way to decrease these metabolites is by converting them to less toxic metabolites. A use of this is sodium thiosulfate in cyanide poisoning. This works by acting as a sulfur donor, which increases the rate of transformation of cyanide into thiocyanate, a less toxic metabolite (Sylvester, D.M., et al. 1983).

Understanding how these antidotes work can lead to a better understanding of medicine as a whole and enhance the possibility of more effective antidotes being found. It is important to understand that many substances can be toxic to the human body, and that caution should always be taken when interacting with foreign substances. If in the event that someone is exposed to one of these substances, the aforementioned antidotes are effective if chosen and administered correctly.

References

Chacko, B., & Peter, J. V. (2019). Antidotes in Poisoning. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine, 23(Suppl 4), S241–S249. https://doi.org/10.5005/jp-journals-10071-23310

Zellner, T., Prasa, D., Färber, E., Hoffmann-Walbeck, P., Genser, D., & Eyer, F. (2019). The Use of Activated Charcoal to Treat Intoxications. Deutsches Arzteblatt international, 116(18), 311–317. https://doi.org/10.3238/arztebl.2019.0311

Li, L., Li, R., Guo, R., Guo, S., Qiao, X., Wu, X., Han, P., Sun, Y., Zhu, X., Wu, Z., Gan, H., Meng, Z., Dou, G., Gu, R., & Liu, S. (2024). Preparation and Evaluation of a Combination of Chelating Agents for the Removal of Inhaled Uranium. Molecules (Basel, Switzerland), 29(23), 5759. https://doi.org/10.3390/molecules29235759

Eddleston, M., Szinicz, L., Eyer, P., & Buckley, N. (2002). Oximes in acute organophosphorus pesticide poisoning: a systematic review of clinical trials. QJM : monthly journal of the Association of Physicians, 95(5), 275–283. https://doi.org/10.1093/qjmed/95.5.275

Lilja, E. E., & Johnson, D. R. (2017). Metabolite toxicity determines the pace of molecular evolution within microbial populations. BMC Evolutionary Biology, 17(1). https://doi.org/10.1186/s12862-017-0906-2

‌Ershad, M., Naji, A., & Vearrier, D. (2019, March 19). N Acetylcysteine. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK537183/

Sylvester, D. M., Hayton, W. L., Morgan, R. L., & Way, J. L. (1983). Effects of thiosulfate on cyanide pharmacokinetics in dogs. Toxicology and applied pharmacology, 69(2), 265–271. https://doi.org/10.1016/0041-008x(83)90307-1