COX-2 inhibitors

A group of anti-inflammatory drugs in which only one of the subtypes of cyclooxygenase (COX) is inhibited is called COX-2 inhibitors or COX-2 inhibitors (generally: coxibs , singular : coxibs ) . The most important sub-forms of this enzyme are cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-2 inhibitors belong to the group of non-opioid analgesics .

Advantages and disadvantages

Prior to the discovery of selective COX-2 inhibitors, classic nonsteroidal anti-inflammatory drugs (NSAIDs) inhibited both COX-1 and COX-2. Inhibiting COX-2 reduces the synthesis of inflammatory mediators , which leads to a decrease in inflammation, but there are also side effects from inhibiting COX-1. When taking COX inhibitors, possible bleeding of the gastric mucosa and a decline in kidney function should be considered.

So-called selective COX-2 inhibitors were developed to specifically treat inflammation while the COX-1 , which is responsible for some important organ functions such as kidney blood flow and protecting the gastric mucosa from stomach acid , remains effective. However, this was only partially successful, since selective COX-2 inhibitors mainly exert their effect on COX-2, but to a lesser extent on COX-1 as well.

When taking selective COX-2 inhibitors, the COX-1 is only slightly influenced, but this does not lead to the absence of side effects. In particular, approval and marketing studies have shown a lower rate of gastroscopic damage to the gastric mucous membrane compared to older NSAIDs . The reason for this is that the synthesis of gastro-protective prostaglandins driven by COX-1 is hardly reduced. However, the clinical significance of these findings is still unclear.

Due to the selective blockade of the COX-2, the COX-1 has more arachidonic acid available, which means that it forms more prostaglandins, including thromboxane A2, which has an aggregatory effect on platelets. Because of this, taking COX-2 selective inhibitors increases the incidence of cardiovascular events (more).

Side effects

The most common side effects mentioned are: upper respiratory tract infection, diarrhea, dyspepsia, upper abdominal discomfort, headache. Peripheral edema and increased blood pressure occur just as frequently with COX-2 selective nonsteroidal anti-inflammatory drugs as with conventional NSAIDs.

In 2004, in the course of a study in the USA, it was suspected that prolonged use of Vioxx ^® ( rofecoxib , a selective COX-2 inhibitor) significantly increased the risk of a heart attack. COX-2 inhibitors reduce the synthesis of prostacyclin , which inhibits platelet aggregation and has a vasodilatory effect, while the COX-1-mediated formation of the functional antagonist thromboxane (which promotes blood platelet aggregation and causes vasoconstriction ) remains unaffected, so that overall an increased tendency to clot results in narrower vessels. Vioxx ^® was therefore withdrawn from the market in September 2004.

In November 2006, lumiracoxib, a COX-2 inhibitor, came onto the market whose structure is not similar to the other coxibs, but diclofenac; whether the risk of cardiovascular (cardiovascular system) side effects is lower remains unclear. The product was withdrawn from the market in 2007 because of serious liver damage.

The COX-2 inhibitor etoricoxib is not approved in the USA due to safety concerns, and in Germany for people aged 16 and over. The parenteral COX-2 inhibitor parecoxib, which is related to valdecoxib , has been withdrawn from the market in Switzerland due to safety concerns and is not approved in the USA.

In vitro data suggest that the anti-inflammatory effects of tocotrienols are also based on the selective inhibition of COX-2.

Coxibs

• Celecoxib
• Etoricoxib (not approved in the US)
• Rofecoxib ( withdrawn from the market in 2004)
• Lumiracoxib ( withdrawn from the market in 2007)
• Parecoxib (not approved in the US)

Individual evidence

1. ↑ Mutschler drug effects; Ernst Mutschler, Gerd Geisslinger, Heyo K. Kroemer, Peter Ruth, Monika Schäfer-Korting Wissenschaftliche Verlagsgesellschaft mbH Stuttgart
2. ↑ Wu, SJ et al. (2008): Tocotrienol-rich fraction of palm oil exhibits anti-inflammatory property by suppressing the expression of inflammatory mediators in human monocytic cells. In: Mol. Nutr. Food. Res. 52 (8): 921-929. PMID 18481320
3. ^ A. Ruß: "Arzneimittelpocket 2010." 15th edition. Börm Bruckmeier Verlag, Grünwald 2009, ISBN 978-3-89862-715-3

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