Review of Pharmacologic Concepts
Early scientific knowledge recognized two basic types of substances: beneficial ones (such as foods and medicines), and harmful ones (those that cause sickness or death). The latter were designated as poisons. Modern science acknowledges that such a strict division is not justified. As early as the sixteenth century, Paracelsus recognized that ‘‘the right dose differentiates a poison and a remedy.’’ Many chemical substances or mixtures exert a whole spectrum of activities, ranging from beneficial to neutral to lethal. Their effect depends not only on the quantity of the substance to which an organism is exposed, but also on the species and size of the organism, its nutritional status, the method of exposure, and several related factors. Alcohol is a good example. Taken in small quantities, alcohol may be harmless and sometimes even medically recommended. However, an overdose causes intoxication and, in extreme cases, death. Similarly, vitamin A is required for the normal functioning of most higher organisms, yet an overdose of it is highly toxic. If the biological effect of a chemical is related to its dose, there must be a measurable range between concentrations that produce no effect and those that produce the maximum effect. The observation of an effect, whether beneficial or harmful, is complicated by the fact that apparently homogeneous systems are, in fact, heterogeneous. Even an inbred species will exhibit marked differences among individuals in response to chemicals. An effect produced in one individual will not necessarily be repeated in another one. Therefore, any meaningful estimation of the toxic potency of a compound will involve statistical methods of evaluation. To determine the toxicity of a compound for a biological system, an observable and well-defined end effect must be identified. Turbidity or acid production, reflecting the growth or growth inhibition of a culture, may be used as an end point in bacterial systems. In some cases, such as in the study of mutagenesis, colony count may be used. Similarly, measures of viable cells, cell protein, or colony count are useful end points in cell cultures.