The first edition of Goodman & Gilman, published in 1941, helped to organize the field of pharmacology, giving it intellectual validity and an academic identity.* That edition began: “The subject of pharmacology is a broad one and embraces the knowledge of the source, physical and chemical properties, compounding, physiological actions, absorption, fate, and excretion, and therapeutic uses of drugs. A drug may be broadly defined as any chemical agent that affects living protoplasm, and few substances would escape inclusion by this definition.” This General Principles section provides the underpinnings for these definitions by exploring the processes of drug invention, development, and regulation, followed by the basic properties of the interactions between the drug and biological systems: pharmacodynamics, pharmacokinetics (including drug transport and metabolism), and pharmacogenomics, with a brief foray into drug toxicity and poisoning. Subsequent sections deal with the use of drugs as therapeutic agents in human subjects.
Use of the term invention to describe the process by which a new drug is identified and brought to medical practice, rather than the more conventional term discovery, is intentional. Today, useful drugs are rarely discovered hiding somewhere waiting to be found. The term invention emphasizes the process by which drugs are sculpted and brought into being based on experimentation and optimization of many independent properties; there is little serendipity.
ADME: absorption, distribution, metabolism, excretion
AHFS-DI: American Hospital Formulary Service-Drug Information
BLA: Biologics License Application
CDC: Centers for Disease Control and Prevention
CDER: Center for Drug Evaluation and Research
DHHS: U.S. Department of Health and Human Services
FDA: U.S. Food and Drug Administration
HCV: hepatitis C virus
HMG CoA: 3-hydroxy-3-methylglutaryl coenzyme A
IND: Investigational New Drug
LDL: low-density lipoprotein
NDA: New Drug Application
NIH: National Institutes of Health
NMEs: New Molecular Entities
NMR: nuclear magnetic resonance
PCSK9: proprotein convertase subtilisin/kexin type 9
PDUFA: Prescription Drug User Fee Act
PhRMA: Pharmaceutical Research and Manufacturers of America
R&D: research and development
SCHIP: State Children’s Health Insurance Program
siRNAs: small interfering RNAs
FROM EARLY EXPERIENCES WITH PLANTS TO MODERN CHEMISTRY
The human fascination—and sometimes infatuation—with chemicals that alter biological function is ancient and results from long experience with and dependence on plants. Because most plants are root bound, many of them produce harmful compounds for defense that animals have learned to avoid and humans to exploit (or abuse).
Earlier editions of this text described examples: the appreciation of coffee (caffeine) by the prior of an Arabian convent, who noted the behavior of goats that gamboled and frisked through the night after eating the berries of the coffee plant; the use of mushrooms and the deadly nightshade plant by professional poisoners; of belladonna (“beautiful lady”) ...