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13 - Antipyretic analgesics
- from SECTION IV - PHARMACOLOGICAL TREATMENT
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- By BURKHARD HINZ, University of Rostock, KAY BRUNE, Friedrich-Alexander University, Erlangen
- Edited by Eduardo D. Bruera, University of Texas, Houston, Russell K. Portenoy, Albert Einstein College of Medicine, New York
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- Book:
- Cancer Pain
- Published online:
- 06 July 2010
- Print publication:
- 12 October 2009, pp 255-271
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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.
10 - Nonopioid analgesics
- from SECTION III - PHARMACOLOGICAL TREATMENT
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- By Burkhard Hinz, Hanns Ulrich Zeilhofer, Kay Brune, Friedrich Alexander University Erlangen-Nuremberg
- Edited by Eduardo D. Bruera, University of Texas, M. D. Anderson Cancer Center, Russell K. Portenoy
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- Book:
- Cancer Pain
- Published online:
- 08 October 2009
- Print publication:
- 23 June 2003, pp 171-187
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- Chapter
- Export citation
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Summary
History of antipyretic analgesics
Fever was the cardinal symptom of disease in the hippocratic medicine. It was assumed to result from an imbalance of body fluids. Therefore, it was the aim of Hippocratic medicine to correct the balances of fluids by either bloodletting, purgation, sweating, or, above all, administering drugs that normalized body temperature. The leading compound in the 18th and 19th centuries for that purpose was quinine, which became scarce in continental Europe during and after the Napoleonic wars as a result of the continental blockade. The emerging synthetic chemistry and drug industry concentrated on producing chemical analogs of quinine and its derivative quinoline as substitutes of the natural products. Moreover, pharmaceutical chemists attempted to isolate substances with similar antipyretic activity from other plants. The results of these efforts were the three prototypes of antipyretic non-opioid analgesic drugs still in use. On the basis of the work of Piria in Italy, Kolbe synthesized salicylic acid as an antipyretic agent in 1859. In 1897, salicylic acid was acetylated by Hoffmann to form aspirin. In 1882, Knorr and Filehne in Erlangen synthesized and tested the non-acidic agent phenazone (antipyrine), which proved to be effective in the clinic. Phenazone was the first pure synthetic drug worldwide. Its introduction as an antipyretic and later as an analgesic led to the discovery of various phenazone derivatives that are still used every year in ton quantities. Almost at the same time, Cahn and Hepp in Strasbourg found that acetanilide may also reduce fever. Acetanilide was introduced as antifebrin, but was later replaced by phenacetin and finally by paracetamol (acetaminophen), which is believed to be safer.