Popular arthritis drug may disrupt heart rhythm, UB research finds

January 24, 2008

Celebrex, a popular arthritis drug that blocks pain by inhibiting an enzyme known as COX-2, has been shown in laboratory studies to induce arrhythmia, or irregular beating of the heart, via a novel pathway unrelated to its COX-2 inhibition.

University at Buffalo researchers discovered this unexpected finding while conducting basic research on potassium channels.

They found that low concentrations of the drug, corresponding to a standard prescription, reduced the heart rate and induced pronounced arrhythmia in fruit flies and the heart cells of rats.

The drug inhibited the normal passage of potassium ions into and out of heart cells through pores in the cell membrane known as delayed rectifier potassium channels, the study showed.

“The adverse effects of drugs like Celebrex and Vioxx based on their selective inhibition of COX-2 currently are a topic of intense discussion in the medical community,” said Satpal Singh, Ph.D., associate professor of pharmacology and toxicology in the UB School of Medicine and Biomedical Sciences and senior author on the study. Vioxx was withdrawn from the market in September 2004.

“We now have shown an important new effect of Celebrex through a totally different pathway, one that is unrelated to the drug’s effect as a pain reducer,” Singh said. “The adverse effect arising from this unexpected mechanism definitely needs to be studied more closely, because the potassium channels inhibited by the drug are present in heart, brain and many other tissues in the human body.

The research was supported by grants from the National Science Foundation to Singh and Randall D. Shortridge, Ph.D., UB assistant professor of biological sciences, to analyze the basic properties of potassium channels.

Aware that COX-2 inhibitors had been shown to produce cardiovascular side effects, the researchers first tested whether Celebrex would affect the heart in fruit flies, a good animal system for studies on heart in other species, including humans.

“When we found an effect on the fly heart, we began looking for the underlying mechanism,” said Singh. “We searched the fly genome and were surprised to find that these flies don’t have cyclooxygenases, the enzymes targeted by Celebrex.

“Because the main effect of the drug in our study was induction of arrhythmia, and arrhythmia is often the result of ion-channel dysfunction,” continued Singh, “we examined the drug’s effect on potassium channels and other ion channels in their models and were struck by the strong inhibition of the potassium channels.”

The researchers now are examining the underlying molecular mechanisms responsible for the drug’s action and its effect on other ion channels that play a prominent role in setting the rhythm of the heart.

“We are trying to determine whether the drug binds directly to the channels or to some other molecule, and if it acts by blocking the pore of the channel through which potassium ions travel or by some other mechanism,” Singh said.

Source: University at Buffalo

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1 / 5 (1) Jan 24, 2008
Why is it that most of the drugs and medications needed by consumers have such dreadful dangerous side effects that are sometimes worse than the disease they are supposed to be treating? If my car breaks down and I take it to the mechanic, I would pay him only after he fixes the car. So, why do we have to pay for medical treatment even when we are not treated but instead the medication causes more dangerous side effects? This is a rip off. I know of a guy who had diabetes and went to the hospital where he was made to stay for 7 days so that they can do all the testing!!! At the end of the week, he was given insulin and aspirin and a bill for $50,000!!! This is robbery in the broad day light. The time has come for patients to assert their rights. If you go to the hospital and you are not treated of the disease so that it stops, you should not pay. Besides you should file a lawsuit for medical malpractice because if the doctor cannot treat the disease, he should not have made the claim in the first place. If he cannot treat the disease, that would mean false claim and a felony and therefore grounds for a malpractice.. If I am a mechanic and the doctor brings his car to me to fix, and if I am unable to fix it, I am sure he would not pay me. The time has come for this scam to stop. Most medical doctors I have seen in US are quacks and extremely incompetent and are disgraces to the medical profession. One of them (Indian Hindu) who I agued with yesterday told me that if his son stops taking his medication, he would trash him. I told him, I hope he does not trash him while I am around otherwise I would call the child protective services on him and make sure he is locked up for child molestation. If a child refuses to take his medication, as a doctor, you should try to understand the reason why. Perhaps, the child may be right. His body may be rejecting the medication. The body is wiser than all the doctors in the world combined. It is sad, doctors these days don't listen to their patients anymore. They are so busy typing none sense in the computer with one finger and getting filthy rich without doing anything to be bothered with paying attention to the patient. I cannot remember one day during the past 20 yrs when any of my doctors called me to say how I was doing. And ofcourse you cannot phone them. They don't answer their phones!!! In addition, in all the big hospitals in US, if you go there for treatment, you must wait in long lines for everything and finally, you may have to wait 8-16 hr before you see a doctor. This includes the emergency rooms. One day, I waited 25 hrs before I could see a doctor, who again happens to be either Pakistani or Hindu and who reluctantly gave me a prescription after about 30 mins of protracted argument with him. His argument was that he did not have to give me any prescription because he was not my doctor!!! In addition, if the doctor writes a prescription and makes a simple mistake in the spelling of your name, the pharmacist would refuse to sell it to you. He would also refuse to phone the doctor to verify over the phone. You would have to go back, search for the doctor, wait in a long line again and if you are lucky, then you can see the doctor again to write a new prescription and spell your name correctly. We all know doctors have the greatest hand writing in the whole world!!! The time has come for US congress to start investigating all American Hospitals in order to fix all the atrocities going on in there. myspace.com/ikbe

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