FIGURE 1–1 Major areas of study in pharmacology. The actions of chemicals can be divided into two large domains. The first (left side) is that of medical pharmacology and toxicology, which is aimed at understanding the actions of drugs as chemicals on individual organisms, especially humans and domestic animals. Both beneficial and toxic effects are included. Pharmacokinetics deals with the absorption, distribution, and elimination of drugs. Pharmacodynamics concerns the actions of the chemical on the organism. The second domain (right side) is that of environmental toxicology, which is concerned with the effects of chemicals on all organisms and their survival in groups and as species.
Prehistoric people undoubtedly recognized the beneficial or toxic effects of many plant and animal materials. Early written records list remedies of many types, including a few that are still recognized as useful drugs today. Most, however, were worthless or actually harmful. In the last 1500 years, sporadic attempts were made to introduce rational methods into medicine, but none was successful owing to the dominance of systems of thought (“schools”) that purported to explain all of biology and disease without the need for experimentation and observation. These schools promulgated bizarre notions such as the idea that disease was caused by excesses of bile or blood in the body, that wounds could be healed by applying a salve to the weapon that caused the wound, and so on.
Around the end of the 17th century, reliance on observation and experimentation began to replace theorizing in physiology and clinical medicine. As the value of these methods in the study of disease became clear, physicians in Great Britain and on the Continent began to apply them to the effects of traditional drugs used in their own practices. Thus, materia medica—the science of drug preparation and the medical uses of drugs—began to develop as the precursor to pharmacology. However, any real understanding of the mechanisms of action of drugs was prevented by the absence of methods for purifying active agents from the crude materials that were available and—even more—by the lack of methods for testing hypotheses about the nature of drug actions.
In the late 18th and early 19th centuries, François Magendie and his student Claude Bernard began to develop the methods of experimental physiology and pharmacology. Advances in chemistry and the further development of physiology in the 18th, 19th, and early 20th centuries laid the foundation needed for understanding how drugs work at the organ and tissue levels. Paradoxically, real advances in basic pharmacology during this time were accompanied by an outburst of unscientific claims by manufacturers and marketers of worthless “patent medicines.” Not until the concepts of rational therapeutics, especially that of the controlled clinical trial, were reintroduced into medicine—only about 60 years ago—did it become possible to adequately evaluate therapeutic claims.
Around the 1940s and 1950s, a major expansion of research efforts in all areas of biology began. As new concepts and new techniques were introduced, information accumulated about drug action and the biologic substrate of that action, the drug receptor. During the last 60 years, many fundamentally new drug groups and new members of old groups were introduced. The last four decades have seen an even more rapid growth of information and understanding of the molecular basis for drug action. The molecular mechanisms of action of many drugs have now been identified, and numerous receptors have been isolated, structurally characterized, and cloned. In fact, the use of receptor identification methods (described in Chapter 2) has led to the discovery of many orphan receptors—receptors for which no ligand has been discovered and whose function can only be guessed. Studies of the local molecular environment of receptors have shown that receptors and effectors do not function in isolation; they are strongly influenced by other receptors and by companion regulatory proteins.