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13 - Antipyretic analgesics

from SECTION IV - PHARMACOLOGICAL TREATMENT

Published online by Cambridge University Press:  06 July 2010

By
BURKHARD HINZ  and
KAY BRUNE
Edited by
Eduardo D. Bruera  and
Russell K. Portenoy
BURKHARD HINZ
Affiliation:
University of Rostock
KAY BRUNE
Affiliation:
Friedrich-Alexander University, Erlangen
Eduardo D. Bruera
Affiliation:
University of Texas, Houston
Russell K. Portenoy
Affiliation:
Albert Einstein College of Medicine, New York
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Summary

Introduction>

Antipyretic (or nonopioid) analgesics are a group of heterogenous substances including acidic (nonsteroidal anti-inflammatory drugs [NSAIDs]) and nonacidic (acetaminophen, pyrazolinones) drugs. Moreover, various selective cyclooxygenase-2 (COX-2) inhibitors with improved gastrointestinal tolerability compared with conventional NSAIDs have been established for symptomatic pain treatment in recent years. This chapter summarizes the pharmacology of all these drugs, with particular emphasis on their rational use based on their diverse pharmacokinetic characteristics and adverse drug reaction profiles. Moreover, the mechanisms underlying their antihyperalgesic action are extensively discussed.

Mode of action of antipyretic analgesics

Inhibition of cyclooxygenase enzymes

In 1971, Vane showed that the anti-inflammatory action of NSAIDs rests in their ability to inhibit the activity of the COX enzyme, which in turn results in a diminished synthesis of proinflammatory prostaglandins. This action is considered not the sole but a major factor of the mode of action of NSAIDs. The pathway leading to the generation of prostaglandins has been elucidated in detail. Within this process, the COX enzyme (also referred to as prostaglandin H synthase) catalyzes the first step of the synthesis of prostanoids by converting arachidonic acid into prostaglandin H2, which is the common substrate for specific prostaglandin synthases. The enzyme is bifunctional, with fatty-acid COX activity (catalyzing the conversion of arachidonic acid to prostaglandin G2) and prostaglandin hydroperoxidase activity (catalyzing the conversion of prostaglandin G2 to prostaglandin H2).

In the early 1990s, COX was demonstrated to exist as two distinct isoforms.

Type
Chapter
Information
Cancer Pain
Assessment and Management
 , pp. 255 - 271
Publisher: Cambridge University Press
Print publication year: 2009

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