In studies in which pain is not the focus, pharmacologic control of pain is usually required. The use of drugs requires consideration of several interacting factors (Short and Van Poznak, 1992).

• What is the clinical goal of drug administration? Common clinical goals include general anesthesia for surgical procedures, lighter general anesthesia for experimental studies that cannot be conducted in awake animals, sedation and analgesia for minor surgical and diagnostic procedures, management of postsurgical pain and pain associated with disease, sedation and tranquilization for the relief of non-pain-induced stress or distress, and temporary restraint.

• What are the pharmacologic actions of the drugs being considered? That is important if they will be used before an experimental study. Knowledge of the pharmacology, pharmacodynamics, duration of action, species-typical actions, and specific actions on the organ systems under study is important for proper interpretation of experimental data. Drugs that are least likely to influence the systems under study should be chosen. Pain and pain-induced distress can be adequately alleviated pharmacologically, but drug actions often confound interpretation of experimental results, because every drug has actions in addition to the one for which it is used (e.g., pain relief). Nevertheless, pharmacologic management is efficacious, often necessary, and usually experimentally acceptable. Knowledge of the so-called side-effects of drugs, however, is important both to the well-being of animals and to an understanding of their potential contributions to experimental outcomes.

• How do species vary in their responses to the drugs being considered, and how are responses affected by other factors? Actions and doses in one animal species might not be relevant in another species. Not only do dosages vary by species, breed, and strain, but other factors—such as sex, environment, age, nutrition, and health status—play a major role; the very young, old, or obese present a greater anesthetic challenge. For example, male mice sleep longer than female mice after the administration of pentobarbital. Environmental factors have been shown to affect hepatic drug-metabolizing enzyme systems (microsomal liver enzymes). Softwood bedding, such as pine or cedar, contains aromatic amines that induce the hepatic microsomal enzymes, thereby increasing barbiturate metabolism and reducing sleeping time. In contrast, hardwood bedding or the absence of bedding (as in the use of wire-bottom cages) allows hepatic enzymes to remain at a resting state, so sleeping times might be longer. A dirty environment might inhibit drug-metabolizing enzymes and thus prolong anesthesia. Anesthetics given repeatedly at short intervals can induce hepatic microsomes and thus increase anesthetic metabolism and decrease sleeping time. Fasting is important especially in herbivorous species, in which ingesta can account for a substantial portion of an animal's body weight; the gastrointestinal tracts of herbivores are not empty after a 24-hour fast.

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