Biomedical subjects

Regina Botting

Publications and source records attributed to Regina Botting.

3 recordsLinked to original sources

PubMed2005

COX-3 and the mechanism of action of paracetamol/acetaminophen.

Paracetamol produces analgesia in the mouse writhing test through a central action which is paralleled by a reduction in brain PGE(2) concentrations. In contrast, diclofenac has a peripheral analgesic action in this test. Paracetamol-induced hypothermia is also accompanied by a reduction in brain PGE(2) concentrations in C57/Bl6 mice. This hypothermic effect of paracetamol was reduced in COX-1 but not in COX-2 gene-deleted mice. These results support the view that analgesia and hypothermia due to paracetamol are mediated by inhibition of a third COX isoenzyme (designated COX-3). In cultured mouse macrophages, COX-2 is induced by treatment with LPS or with high concentrations of diclofenac. Diclofenac-induced COX-2 is inhibited with low concentrations of paracetamol, whereas LPS-induced COX-2 is insensitive to paracetamol inhibition. The mechanisms of induction and possibly the functions of these two COX-2 enzymes are also different.

Acetaminophen↗

PubMed2004

Antipyretic therapy.

Antipyresis can be achieved by physical methods such as cooling the body with tepid water or by pharmacological means such as the administration of antipyretic drugs. The nonsteroid anti-inflammatory drugs (NSAIDs) including aspirin, have been used to combat fever since the end of the 19th century and the analgesic antipyretics, from about the same time. Most of the antipyretic analgesics such as acetanilide and phenacetin are no longer used in therapy because of their toxicity. However, the metabolite of these two drugs, acetaminophen, became a highly popular antipyretic in the 1950s and is now the antipyretic of first choice in most developed countries. The disadvantages of administering NSAIDs is their gastrotoxicity manifested as irritation, ulcers and bleeding of the stomach mucosa. Acetaminophen also is toxic to the liver in doses only slightly above the therapeutic dose. Thus, selective COX-2 inhibitors, which do not damage the stomach and are free fom hepatotoxicity, may be the drugs of choice for reducing fever in the future.

Analgesics↗

PubMed2003

COX-1 and COX-3 inhibitors.

Low doses of aspirin reduce both pain and fever, whereas the anti-inflammatory action of aspirin requires a much higher dose. It is possible that inhibition of cyclooxygenase (COX)-1 is the major action of aspirin involved in its analgesic and antipyretic effects, and inhibition of COX-2 is responsible for its anti-inflammatory action. We compared the analgesic effects of an aspirin-like drug (diclofenac) and a centrally acting analgesic (paracetamol) in the mouse stretching test and confirmed that the analgesic action of the aspirin-like drug was peripheral. Two possible sites have been postulated for the antipyretic action of non-steroid anti-inflammatory drugs; (a) inhibition of COX in endothelial cells of hypothalamic blood vessels or (b) inhibition of COX synthesising prostaglandins near sensory receptors of sub-diaphragmatic vagal afferents. The antipyretic action of aspirin may be mediated by inhibition of COX-3 in hypothalamic endothelial cells or by inhibition of COX-1 localised close to sensory receptors of peripheral vagal afferents. It is also possible that both enzymes are involved in the antipyretic action of aspirin. Whereas lipopolysaccharide (LPS)-induced fever is attenuated in COX-2 gene-deleted mice, suggesting that COX-2 is responsible for this type of fever, the COX-1 gene may also be important in temperature regulation and in mediating the pyresis that occurs in the absence of infection.

Analgesics, Non-Narcotic↗