Arthritis drug celecoxib can adversely affect heart rhythm

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COX-2 inhibitors like Celecoxib have come under scrutiny lately due to adverse cardiovascular side-effects stemming from COX-2 reduction. In both fruit fly and rat models, researchers reveal another adverse effect of Celecoxib; this drug can induce arrhythmia. More interestingly, this effect is independent of the COX-2 enzyme.

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer under the brand name Celebrex. In some countries, it is branded Celebra. Celecoxib is available by prescription in capsule form.

Satpal Singh and colleagues (Department of Pharmacology and Toxicology, State University of New York at Buffalo) tested various Celecoxib doses on the heart rate of Drosophila, a good model for human cardiac pharmacology. To their surprise, administering 3 ??m Celecoxib (not much higher than the plasma levels in humans taking the drug) reduced heart rate and increased beating irregularities, while 30 ??m was enough to stop the heart within a minute.

The surprise arises from the fact that Drosophila do not have COX-2 enzymes. Rather, Celecoxib could directly inhibit the potassium channels that help generate the electric current that drives heartbeat.

The researchers could achieve similar heart-stopping results in rat cardiac cells, whereas aspirin, another potent COX-2 inhibitor, had no effect, confirming that another mechanism is at work. The drug also inhibited rat and human potassium channels expressed in a human cell line.

Singh and colleagues point out that since these arrhythmia effects bypass COX-2, it is unclear if other COX-2 inhibitors would yield similar results. They also stress it is too early to speculate on human effects, although their results suggest Drosophila are a valuable tool to investigate other COX-2 drugs.

Source: American Society for Biochemistry and Molecular Biology, USA


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