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Recognition and Alleviation of Pain and Distress in Laboratory Animals
of the nictitating membrane in some animals, and abolition of conditioned reflexes. It must be emphasized that animals under the sedation produced by tranquilizers can still react in a coordinated manner. A large animal can still kick with full force in reaction to painful stimuli, a vicious animal can still bite, and nonhuman primates can become aroused unexpectedly. The degree of sedation and inactivity produced by the tranquilizers in many instances depends on the excitability of the animal being treated. That is especially true in wild animals: the tranquilization of free-living and captive undomesticated animals might not be possible, and more potent drugs might be necessary (Graham-Jones, 1960, 1964). It is also true of vicious animals; i.e., tranquilizers might produce insufficient restraint for safe management of extremely high-strung nervous animals. In those circumstances, neuroleptanalgesia might have to be administered with a combination of a tranquilizer and an opioid. In stallions, many phenothiazine tranquilizers cause erections and temporary or permanent prolapse of the penis. In horses, phenothiazines and butyrophenones cause involuntary and hallucinatory activity (Muir et al., 1989).
The major action of the phenothiazines is antagonism of the central dopamine receptors. In addition to their sedative properties, the phenothiazines and the related butyrophenones (e.g., droperidol) produce a dose-dependent decrease in motor activity. At greater doses, they produce a cataleptic state that includes rigidity, tremor, and akinesia. The phenothiazines are also useful in some species as antiemetics. However, they have important anticholinergic, antiadrenergic, and antihistaminic effects, which often lead to undesirable or unanticipated side effects and unpredictable drug interactions.
The two most commonly used phenothiazines are promazine and acetylpromazine. They produce numerous cardiovascular effects through central and peripheral actions on the sympathetic nervous system and the CNS and direct actions on vascular and cardiovascular smooth muscle. The CNS manifestation is inhibition of centrally mediated pressor reflexes, which reduces both vascular tone and the ability to respond reflexively to alterations in the cardiovascular system. The peripheral effects are related to α2-adrenergic receptor blockade.
Phenothiazines are commonly administered intravenously to animals in the standing position, especially farm animals. The cardiovascular actions have a more rapid onset than the sedative actions, and orthostatic hypotension might explain the occasional collapse. The extent of hypotensive effects of a tranquilizer varies and depends on the state of the cardiovascular system and the sympathetic tone when the drug is administered. Fatigue, hypovolemia, excitement, and trauma can increase sympathetic tone as a part of the adaptive homeostatic process. The administration of a sympatholytic drug under those circumstances can have a profound effect (Bahga and Link, 1966). Phenothiazines lessen the ability of the cardiovascular system to compensate for changes in vascular volume, changes in position, and