Pharmacology of analgesia. Review article I.

The clinical assessment and management of pain remains one of the most impo rtant and difficult problems in medical and veterinary practice. Though the responsibility of the veterinary surgeon in relieving of pain is obvious, analgesics are not used as frequently as required, in spite of the fact tha t during recent years a number of novel analgesics have been marketed. The reasons for the limited use of analgesics in veterinary practice are critic ally summarised. The control of pain requires a knowledge of pain mechanism s and an understanding of the drugs used for this purpose as well as a comm itment to the patient. This and the following articles give a short overvie w about some pharmacological aspects of analgesia considering mainly the me chanisms of action of analgesics with the aim to provide information which can be utilized in daily practice. Analgesics are drugs which relieve pain without causing unconsciousness or modifying other sensory modalities. Base d on their site of action they can be categorized into two main groups (Tab le I), however, there is some overlap between them. This article describes the main pharmacological and side effects of non-steroidal anti-inflammator y drugs (NSAIDs) and their applicability in the therapy, whereas the action s and use of other analgesics are addressed in a separate paper of the next issue. In comparison with the anti-inflammatory corticosteroids and narcotic analg esics, the history of designation of NSAIDs is discussed. The chemical clas sification of the most frequently used NSAIDs is presented in Table 2. Most NSAIDs act partly and in some cases perhaps solely through inhibition of t he cyclo-oxigenase which is concerned with the generation of an important s ubgroup of eicosanoids, the prostanoids. The physiological and pathological role of prostanoids is considered. Cyclo-oxygenase (COX) presents in two g enetically determined forms: COX-1 and COX-2. The localization, production of COX-1 and COX-2 and their role in the physiological regulations and path ological conditions are described together with the differences in the affi nity of various NSAIDs to these enzyme subgroups. The main pharmacological effects (analgesic, anti-inflammatory and antipyre tic effects) and undesirable side effects (gastrointestinal disturbances, n ephropathy, inhibition of thrombocyte aggregation, bleeding) of NSAIDs can be fairly well explained by a common pathway, i.e. the inhibition of COX-1 and COX-2 which in turn results in a decreased synthesis of prostanoids. Ho wever, the extremely large variation in efficacy (see Table 3) and toxicity of NSAIDs suggest that other mechanisms may be involved in their action. T hese recently emerging data are discussed with reference to the modern NSAI Ds such as carprofen, ketoprofen or nabumeton. Special attention is given t o the clinically important fact that due to the variation in potency and es pecially the different metabolism and kinetic profiles of NSAIDs in various animal species, extrapolation of dose rates between species is impossible. The therapeutic uses of NSAIDs, including the perioperative application of modern NSAIDs, are described.