Poisons

Poisons are substances that are harmful to living organisms. It is said that “the dose makes the poison” because almost any substance can be poisonous at high enough concentrations, especially many substances used as medi­cines.

Poisons include compounds of biological origin and chemicals manu­factured by humans. Biological poisons, also known as toxins, are produced by some members of every living kingdom, including bacteria, fungi, protists, plants, and animals. The chemical industries produce thousands of chemicals, many of which are poisonous. Regulation of workplace exposure to these is the responsibility of the Occupational Safety and Health Agency, or OSHA. The Environmental Protection Agency (EPA) oversees cleanup of toxic wastes and spills.

Exposure

There are three major routes of exposure for poisons: absorption through the skin, inhalation into the lungs, and ingestion in the gut. Skin forms a barrier against many poisons, but its large surface area provides a route of entry for liquids especially. Inhalation provides a rapid route of entry di­rectly into the bloodstream for small, volatile molecules. The enzymes and acids of the gastrointestinal tract inactivate some ingested poisons, but the long transit time and high surface area of the gut mean that an ingested poi­son is likely to enter the bloodstream if not inactivated.

Most poisons act acutely, meaning their toxic effects come on very quickly after exposure. In contrast, heavy metals such as lead and mercury accumulate slowly in the fatty tissue of the body, and chronic exposure to low doses can cause poisoning.

Mechanisms

Poisons disrupt metabolic processes or destroy tissue through chemical re­actions with cells. While the number of specific mechanisms of action is large, there are several broad means by which many poisons exert their ef­fects. The list below is not comprehensive.

Oxygen Deprivation. The brain consumes large amounts of oxygen and can­not survive if deprived of it for more than ten minutes. Oxygen deprivation may occur if the respiratory muscles cannot deliver adequate air to the lungs, if the lungs cannot absorb adequate oxygen from the air, or if the blood can­not carry the oxygen to the brain.

Barbiturates and benzodiazepines, drugs prescribed as sedatives, de­press activity in the brain center that controls the respiratory muscles, thus preventing those muscles from working sufficiently. Respiratory muscle paralysis may be caused by ingestion of botulinum toxin, one of the most poisonous substances known. It is formed by the bacterium Clostridium botulinum, a contaminant of improperly canned food. Botu­linum toxin prevents release of acetylcholine by neurons at the neuro­muscular junction. Without this neurotransmitter, the respiratory muscles cannot contract.

Absorption of adequate oxygen can be interrupted when otherwise harmless gases, such as nitrogen or carbon dioxide, are present in high con­centration. In 1986, a massive release of dissolved carbon dioxide from Lake Nyos in Cameroon, Africa, asphyxiated eighteen hundred people in the sur­rounding villages. Hemoglobin carries oxygen in the bloodstream. Carbon monoxide binds to hemoglobin, displacing oxygen and preventing its trans­port. Carbon monoxide is produced by combustion and is found in car ex­haust and furnace smoke.

Cardiac Toxicity. The heart muscle relies on chemical signals to control the rate and force of its contractions. Digitalis, derived from the foxglove plant, is prescribed for congestive heart failure to increase heart output. In slightly larger doses, it is deadly. Related compounds are produced by various South American frogs of the genus Dendrobates, and are used on ar­row tips for hunting.

Digitalis, derived from the foxglove plant, is prescribed for congestive heart failure to increase heart output. In slightly larger doses, it is deadly.

Mitochondrial Poisons. Most cells in the body are supplied with fuel by subcellular structures called mitochondria. One step of the energy- producing reactions, oxidative phosphorylation, relies on electron- carrying proteins called cytochromes. Cyanide binds permanently to these cytochromes, preventing them from carrying electrons and thus in­activating them. Another step in these reactions requires a buildup of H+ ions across the mitochondrial membrane. Dinitrophenol, a chemical used in dye manufacture, is a membrane-soluble H+ carrier. By carrying H+ ions across the mitochondrial membrane, dinitrophenol interrupts this step. Impaired energy production affects all cells, especially brain and heart cells.

Liver and Kidney Poisons. The liver is the principal site of poison detox­ification. It has many different types of enzymes that attack and degrade the wide variety of molecules to which the body may be exposed. Inhalants such as glues, gasoline, or other solvents cause direct tissue damage to the liver, leading to liver failure. The kidneys excrete most poisons or their break­down products. Kidneys may be damaged from exposure to poisons, or by accumulation of compounds that cannot be excreted.

Mutagens and Carcinogens. Chemicals that cause changes in deoxyri­bonucleic acid (DNA) sequence, or mutations, are called mutagens. If these changes prompt the cell to begin dividing, the cell may become cancerous. Substances that cause cancer are called carcinogens. Inhaled asbestos fibers can cause lung cancer, as can chemicals in cigarette smoke.

Treatment

Antidotes are available for very few poisons. Snakebite, for instance, may be treated with antivenin, which provides antibodies that inactivate the poison­ous venom. However, in most cases of poisoning, medical treatment focuses on removing the poison from the body when possible, and maintaining res­piration and circulation until the toxic effects are reduced as the compound is metabolized and excreted over time. Poison control centers in every state excrete deposit out- maintain telephone hotlines to deal with poisoning emergencies. If a victim is in medical distress, 911 should be called immediately.

References

American Association of Poison Control Centers. http://www.aapcc.org/.

Medical Toxicology On-Line. http://toxikon.er.uic.edu/.

Turkington, Carol. The Poisons and Antidotes Sourcebook, 2nd ed. New York: Check­mark Books, 1999.