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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 (., 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 pharmacokin