Basic and Clinical Pharmacology 15e

Book Preface

CASE STUDY
A 78-year-old woman is brought to the hospital because of suspected aspirin overdose*. She has taken aspirin for joint pain for many years without incident, but during the past year, she has exhibited signs of cognitive decline. Her caregiver finds her confused, hyperventilating, and vomiting. The caregiver finds an empty bottle of aspirin tablets and calls 9-1-1. In the emergency department, samples of venous and arterial blood are obtained while the airway, breathing, and circulation are evaluated. An intravenous (IV) drip is started, and gastrointestinal decontamination is begun. After blood gas results are reported, sodium bicarbonate is administered via the IV. What is the purpose of the sodium bicarbonate?

Pharmacology can be defined as the study of substances that interact with living systems through chemical processes. These interactions usually occur by binding of the substance to regulatory molecules and activating or inhibiting normal body processes. These substances may be chemicals administered to achieve a beneficial therapeutic effect on some process within the patient or for their toxic effects on regulatory processes in parasites infecting the patient. Such deliberate therapeutic applications may be considered the proper role of medical pharmacology, which is often defined as the science of substances used to prevent, diagnose, and treat disease. Toxicology is the branch of pharmacology that deals with the undesirable effects of chemicals on living systems, from individual cells to humans to complex ecosystems (Figure 1–1). The nature of drugs—their physical properties and their interactions with biological systems—is discussed in part I of this chapter.
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.

New drugs are added every year; they are needed for several reasons including: (1) increasing resistance by bacteria and other parasites; (2) discovery of new target processes in diseases that have not been adequately treated; and (3) recognition of new diseases. Furthermore, a dramatic increase has occurred in the number of large molecule drugs (especially antibodies) approved during the last two decades. The development of new drugs and their regulation by government agencies are discussed in part II.
*The author thanks Barry Berkowitz, PhD, for contributions to the second part of this chapter in previous editions.
THE HISTORY OF PHARMACOLOGY
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. Beginning about 1500 years ago, 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, concepts based 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 systematically 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 cellular 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