Daniel Simmons discovered the COX-2 enzyme in 1998. Of course it was a revolutionary break though. COX-1 or cyclooxygenase-1 enzyme is responsible for maintenance and protection of the gastrointestinal tract, while cyclooxygenase-2 enzyme (COX-2) - for inflammation and pain.

COX-2 inhibitors, newly developed drugs for inflammation, selectively block this COX-2 enzyme. This process (blocking) impedes the production of the chemical messengers (prostaglandins, or “bad prostaglandins” as they’re often called) that cause the pain and swelling of arthritis inflammation. They block only COX-2 enzyme and not the COX-1 enzyme (thereby reducing gastrointestinal toxicity). That is why COX-2 inhibitors are the newest of the class of NSAIDs (nonsteroidal anti-inflammatory drugs) that have many differences from traditional NSAIDs.

Because of the serious damage of the side effects several drugs were withdrawn from the market, what happened for example with Vioxx that is now no longer on the market (since September 2004) and Bextra (since April 2005).

Side effects of COX-2 inhibitor drugs

Like all medications, COX-2 inhibitors carry a risk of side effects. The frequency of the side effects varies between users, as well as depend on the type of the drug itself and its dosage.

• Cardiovascular side effects: stroke, myocardial infarction (heart attack), and thrombosis (blood clots).

On September 30, 2004, Merck and Co. released a study linking the drug to increased risk of heart attacks and strokes and voluntary withdrew rofecoxib (Vioxx) from the market. They also said that its arthritis painkiller Arcoxia does not increase the risk of heart attacks, in a study underscoring the difference between this drug and its withdrawn-from-the-market blockbuster Vioxx. On the American Heart Association meeting new study showed that Arcoxia is safer than Vioxx in terms of heart attack risk. However, Arcoxia showed mixed results in preventing gastro-intestinal bleeding.

Nevertheless, new researches on the topic show that rates of heart attack, stroke or death in patients with arthritis is nearly identical in those taking Merck's Arcoxia (etoricoxib) and those taking the traditional painkiller - Diclofenac.

The possible way out for the patients is either to receive the less COX-2 selectivity of other NSAIDs or to get co-administration of low dose aspirin along with the treatment (as COX -2 inhibition in this case is compensated with the cardioprotection effect of COX-1 inhibition).

• Stevens Johnson Syndrome - SJS - a serious allergic skin reaction - inflammation of the skin and mucous membranes, that are present in many organs throughout the body, such as the eyes, digestive system, lungs, and respiratory system. It can be caused by an allergic reaction to certain COX-2 inhibitors, particularly Bextra and Celebrex. It begins as a rash and can progress into serious skin scarring and potentially death. Then over some time, the rash spreads to other parts of the body and forms as an elevated skin lesions.

• Serious side effects on the gut, such as ulceration, bleeding or perforation of the stomach or intestinal lining. Also abdominal pain, constipation, diarrhoea, nausea, vomiting and indigestion. NSAIDs work by affecting chemicals in the body that cause inflammation, but along with it they also affect the same group of chemicals that is located in the stomach, thus causing indigestion and some cases of ulceration (an inflamed open sore on the skin of the stomach). This side effects is more likely to occur in people taking high doses of the medicine and elderly people.

• Liver, kidney or blood disorders.
• Chest pain.
• Some may cause dizziness or sleepiness and so may affect your ability to drive or operate machinery safely by causing visual disturbances. Can cause fatigue.

• Headache and flu-like symptoms.
• Swelling of the legs and ankles due to fluid retention (oedema).
• Depression and anxiety.
• Insomnia.
• Muscle cramps, pins and needles or numb sensations.
• Epistaxis (nosebleeds).
• Shortness of breath.
• Sensation of ringing or other noise in the ears (tinnitus).
• Very rarely, NSAIDS may cause toxic epidermal necrolysis and exfoliative dermatitis. It is most likely to happen in the first month of treatment.

Mind also, that while taking these medications you may do not notice the symptoms of other diseases, as NSAIDs may mask the signs and symptoms of infection (for example fever and inflammation). Use COX – 2 inhibitors very carefully if you have a history of disorders affecting the stomach or intestines or if you are with impaired kidney or liver. Such patients should have their kidney function (and other related organs) monitored while taking this medicine. Perhaps, they also should take regular blood tests to monitor their liver function, especially during long-term treatment.

If the patient has risk factors for heart disease or stroke, such as diabetes, high cholesterol or smoking, doctor will need to assess the overall benefits and risks before deciding if this medicine is suitable for him or her. Low dose (the lower is the better) could be acceptable, and the dose should not be exceeded.

COX-2 inhibitors should not be used by children andadolescents under 18 years of age, by pregnant women during the third trimester, by breastfeeding mummies, by people with decreased kidney function, liver disease, bleeding from the gut (and peptic ulcer), inflammatory bowel disease, heart failure, angina and by those who have a history of stroke, heart attach,have poor circulation in the arteries of the legs or feet or allergic reaction to some kind of NSAIDs (as aspirin and ibuprofen).

Do not forget to consult your doctor while treatment if you experience any of the mentioned side effects. With doctor’s help you would achieve the proper balance between the benefit of the medicine treatment and its adverse effects.

As for the COX – 2 inhibitors, data suggests that COX-1 and COX-2 enzymes each serve as a "check and balance" to one another. If one type of COX enzyme is reduced too much in the body, then the other enzyme will create a dangerous imbalance.

Valentyna Ant.