Chapter 9: Principles of Clinical Toxicology

INTRODUCTION

Toxicology is the study of the adverse effects of substances on living organisms. Any substance is considered a poison when exposure results in a damaging physiological effect (toxic effect). Among the agents that can produce toxic effects are pharmaceuticals, illicit drugs, plants and botanicals, and myriad chemicals and pollutants. Chapter 76 focuses on environmental toxicology. This chapter focuses on clinical toxicology, the discipline of toxicology that studies undesired effects of pharmaceutical therapies in humans and the effects and treatment of poisoning.

Toxicological testing is performed in preclinical studies to assess for the toxicity of a substance in animals and in in vitro models (see Chapters 1 and 76). Additional studies, including carcinogenicity, teratogenicity, and effects on fertility, are performed concurrently with the first stages of a clinical trial. More adverse effects may be discovered in postmarketing surveillance as more doses are administered and more patients are exposed to the drug (see Chapter 9).

ABBREVIATIONS

DOSE-RESPONSE

Conventional Dose-Response Curves

Dose-response relationships are graded in an individual and quantal in the population (see Figures 3–7 and 3–9). In a graded dose-response, the magnitude of an individual’s response usually increases as the dose of the drug is increased. In a quantal dose relationship, the percentage of the population that responds increases as the dose of the drug increases, but the response is only judged to be either present or absent in a given individual. This quantal dose-response phenomenon is used to determine the LD₅₀ (median lethal dose) of drugs, as defined in Figure 9–1A.