Cox-2 inhibitors

COX-2 inhibitors or COX-2 inhibitors are a group of anti-inflammatory drugs in which only one (COX-2) of the sub-forms of cyclooxygenase (COX) is inhibited. COX-2 inhibitors belong to the group of non-opioid analgesics.

The so-called selective COX-2 inhibitors were developed with the aim of improving the side-effect profile of the non-selective COX inhibitors by selectively inhibiting COC-2 (especially gastric tolerance). This goal was achieved, but other serious side effects were observed.

Taking selective COX-2 inhibitors has little effect on COX-1, the other subforms of cyclooxygenase. However, the selective blockade of cyclooxygenase -2 of COX-1 makes a higher supply of arachidonic acid available. This leads to an increased prostaglandin synthesis, among others of thromboxane A2. This shifts the balance between the prothrombotically active TXA2 and the antithrombotically active PGI2 in favour of TXA2. This leads to an increased aggregatory effect on thrombocytes, so that the incidence of cardio- and cerebrovascular events increases significantly under this therapy (myocardial infarction, cerebral infarction). This effect is a group-specific phenomenon that applies to all COX-2 inhibitors!

The most common side effects are: upper respiratory tract infection, diarrhea, dyspepsia, upper abdominal pain, headache. Peripheral edema, increase in blood pressure are as common with COX-2 selective non-steroidal anti-inflammatory drugs as with conventional NSAIDs.

For example, the use of rofecoxib (Vioxx®) showed a significantly increased rate of vascular complications. Rofecoxib was therefore withdrawn from the market in September 2004. In 2006, lumiracoxib, a COX-2 inhibitor, was launched on the market, which had to be withdrawn due to serious heptatoxic damage.

The COX-2 inhibitor etoricoxib was not approved in the USA due to safety concerns. The COX-2 inhibitor parecoxib, which is related to valdecoxib, was withdrawn from the market in Switzerland due to safety concerns and has not been approved in the USA.