Chapter 7 Toxicology
General Principles
Terminology
General Mechanisms of Toxicity
Target Organs
Toxicity may be systemic, affecting the whole body, or it may be largely confined to select target organs, the so-called toxic effect organs. Some organs, such as the liver, brain, lungs, heart, and kidney, play a central role in poisonings (Figure 7-1). When toxicity is site specific, the word toxic is preceded by an indication of the specific target organ. Thus, hepatotoxicity refers to effects on the liver, nephrotoxicity refers to effects on the kidney, ototoxicity refers to effects on the auditory system, and so on. A number of factors interact to determine the susceptibility of organs to toxic effects. These include the organ’s anatomic location, blood flow, metabolic processes and activity, affinity for the toxicant, and capacity for self-repair. Major toxic effect organs include the following:
Risk Assessment
Because virtually all substances are potentially toxic, key questions in toxicology are how much risk is associated with a particular substance and under what conditions does this risk become apparent? In addition, the level of acceptable risk will vary. In some circumstances, very toxic substances (e.g., anticancer drugs) are used therapeutically despite their known toxic effects because the benefits of such treatments outweigh the risks. Accordingly, risk assessment is a primary consideration in the management of toxic events (Figure 7-2).
Key factors contributing to risk assessment include the following:
General Strategies for Management of Toxic Events
In addition to specific treatments, a number of generalized treatment strategies can be used in poisonings (Figure 7-3). These are toxicokinetic treatment strategies targeted at reducing or preventing the absorption of the toxicant, at reducing the distribution of the toxicant, at manipulating biotransformation to reduce formation of the toxicant, or at hastening excretion of the toxicant. These approaches rely heavily on the concepts of pharmacokinetics presented earlier, which will not be repeated here. These generalized approaches are very useful in situations in which there are no specific antidotes or the causative toxicant(s) and/or modes of action are not sufficiently well defined to allow application of a specific antidote.
Reduction or Prevention of Absorption
Gastric Lavage
Activated Charcoal
Activation of charcoal by oxidization increases its adsorptive surface area. The large surface area of charcoal is capable of adsorbing many toxicants, thus sequestering them in the gut. Because only free molecules are able to diffuse across membranes, reduction of the concentration of free toxicant in the gut by charcoal greatly reduces absorption into the bloodstream (Figure 7-4). This treatment is administered as a slurry of the activated charcoal powder.