Effects of Chemical Interaction

Because of the large number of different chemicals an individual may come in contact with at any given time (workplace, medications, diet, hobbies, etc.), it is necessary to consider how different chemicals may interact with each other. Interactions can occur through various mechanisms, such as alterations in absorption, protein binding, and the biotransformation and excretion of one or both of the interacting toxicants. In addition to these modes of interaction, the response of the organism to combinations of toxicants may be increased or decreased because of toxicologic responses at the site of action.

1. An additive effect occurs when the combined effect of two chemicals is equal to the sum of the effects of each agent given alone (example: 2 + 3 = 5). The effect most commonly observed when two chemicals are given together is an additive effect.

2. A synergistic effect occurs when the combined effects of two chemicals are much greater than the sum of the effects of each agent given alone (example: 2 + 2 = 20). For example, both carbon tetrachloride and ethanol are hepatotoxic compounds, but together they produce much more liver injury than the mathematical sum of their individual effects on liver at a given dose would suggest.

3. Potentiation occurs when one substance does not have a toxic effect on a certain organ or system but when added to another chemical makes that chemical much more toxic (example: 0 + 2 = 10). For example, Isopropanol is not hepatotoxic, but when it is administered in addition to carbon tetrachloride, the hepatotoxicity of carbon tetrachloride is much greater than is the case when it is given alone.

4. Antagonism occurs when two chemicals administered together interfere with each other's actions or one interferes with the action of the other (example: 4 + 6 = 8; 4 + (–4) = 0; 4 + 0 = 1).

There are four major types of antagonism: functional, chemical, dispositional, and receptor.

·                  Functional antagonism occurs when two chemicals counterbalance each other by producing opposite effects on the same physiologic function. For example, the marked fall in blood pressure during severe barbiturate intoxication can be antagonized effectively by the intravenous administration of a vasopressor agent such as norepinephrine or metaraminol.

·                  Chemical antagonism or inactivation is simply a chemical reaction between two compounds that produces a less toxic product. For example, chelators of metal ions decrease metal toxicity and antitoxins antagonize the action of various animal toxins.

·     Dispositional antagonism occurs when the absorption, biotransformation, distribution, or excretion of a chemical is altered so that the concentration and/or duration of the chemical at the target organ are diminished. Thus, the prevention of absorption of a toxicant by ipecac or charcoal, increased activity of metabolizing enzymes with enzyme inducers, and the increased excretion of a chemical caused by the administration of a diuretic are examples of dispositional antagonism.

·             Receptor antagonism occurs when two chemicals that bind to the same receptor produce less of an effect when given together than the addition of their separate effects (example: 4 + 6 = 8) or when one chemical antagonizes the effect of the second chemical (example: 0 + 4 = 1). Receptor antagonists often are termed blockers.