Chapter 3
- Basic Principles of Pharmacology Related to Anesthesia
- Steven L. Shafer
- Debra A. Schwinn
Anesthesia involves administration of drugs to produce therapeutic
effects while minimizing undesirable side effects or toxicity. Anesthesiologists
give drugs to provide analgesia, amnesia, hypnosis, and muscle relaxation; they also
administer drugs to manipulate major organ systems pharmacologically to maintain
homeostasis and prevent injury. The therapeutic objective is to achieve adequate
drug concentrations at specific sites of action to produce the desired effect. The
anesthesiologist must select and administer appropriate drugs to provide tissue and
receptor concentrations lower than those that produce unacceptable toxicity and higher
than those that fail to provide effective therapy (i.e., within the therapeutic window).
The empirical approach to drug administration consists of selecting
an initial dose and then titrating subsequent doses based on the clinical responses
of the patient. The ability of the anesthesiologist to predict clinical response
and to select optimal doses is part of the art of anesthesia. Continued research
in the basic and clinical pharmacology of anesthetic drugs has produced guidelines
by which the science of anesthesiology can enhance the art.
This chapter is divided into three major sections: pharmacokinetic
principles, pharmacodynamic principles, and the principles that underlie variability
in drug response. The pharmacokinetics section describes the relationship between
drug administration and drug concentration at the site of action. Essential components
of pharmacokinetics include volumes of distribution of drug within the tissues, systemic
clearance (usually hepatic metabolism for intravenous anesthetics), biologic activity
of metabolites, transfer of drugs between plasma and tissues, and binding of drugs
to circulating plasma proteins. This section introduces the physiologic processes
that determine pharmacokinetics and the mathematical models used to relate dose to
concentration.
The pharmacodynamics section explores the relationship between
drug concentration and pharmacologic effect. The broad areas of transduction of
biologic signals, including fundamental receptor theory and structure, the role of
new developments in molecular biology, and clinical evaluation of drug effects are
presented.
The third section explores the processes that contribute to variability
in drug response. They include pharmacogenetics, influence of the patient's physiology
on pharmacokinetics and pharmacodynamics, and drug interactions.
An understanding of fundamental pharmacokinetic and pharmacodynamic
principles provides the anesthesiologist with a scientific foundation for using drugs
to achieve specific therapeutic objectives. These principles form the basis for
the application of pharmacologic science to the practice of anesthesia. Exploring
the basics of pharmacogenetics provides state-of-the-art pharmacologic and genetic
information to understand important sources of variability in drug response.
