Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chemical imbalance may explain painkiller’s cardiac danger

14.09.2005


The increased rate of cardiovascular complications in patients taking the cox-2 inhibitor painkiller rofecoxib (Vioxx) may result from a chemical imbalance, according to an animal study in the September Cell Metabolism. The findings suggest that low-dose aspirin might prevent the cardiac damage of such drugs and might also lead to the development of new anti-inflammatory drugs without the adverse side effects, the researchers said.



Earlier studies in humans have found that cox-2 inhibitors cause a decline in prostacyclin, a chemical that normally keeps blood vessels open and prevents blood clots. That drop occurs without a change in concentration of thromboxane, a related agent that constricts vessels and promotes clot formation.

The new study by researchers at Duke University and Durham VA Medical Centers found that, in mice prone to high blood pressure, an inability to respond to prostacyclin led to cardiac complications, including hypertension, enlarged hearts and severe scarring of the heart. Moreover, they showed, unrestrained action of thromboxane in the absence of prostacyclin accentuated the intensity of cardiac damage caused by the high blood pressure.


"The current results suggest that such a chemical imbalance in patients taking selective cox-2 inhibitor painkillers may present a cardiovascular hazard--particularly for people already predisposed to high blood pressure," said study author Thomas Coffman.

"Hypertension is the most common cardiovascular complication associated with cox-2 inhibition, yet not everybody who takes the drugs develops high blood pressure," he continued. "The mice appear to have characteristics similar to the subset of patients who are prone to experience this side effect."

Cox-2 inhibitors and other nonsteroidal, anti-inflammatory drugs (NSAIDs)--including aspirin and ibuprofen--all reduce inflammation and pain by blocking the function of cyclo-oxygenases, also known as cox enzymes. The cox enzymes, cox-1 and cox-2, normally produce prostanoids--a family of related chemicals, including prostaglandins and thromboxanes, with many important functions throughout the body.

Prostaglandins produced by both enzymes promote inflammation, pain, and fever, while others made by cox-1 protect the stomach from the damaging effects of acid. The cox-1 and cox-2 enzymes, respectively, also produce thromboxane and prostacyclin.

Traditional NSAIDs relieve pain and inflammation by simultaneously blocking the function of both cox enzymes, Coffman explained. In contrast, rofecoxib and other cox-2 inhibitors selectively limit cox-2, thereby avoiding the gastrointestinal complications of over-the-counter NSAIDs.

A 2004 study, however, found an early rise in blood pressure and an increased rate of heart attack and stroke in patients treated with rofecoxib for more than 18 months. Last year, the manufacturer withdrew the drug from the market.

The current findings may lead to new drugs that avoid the pitfalls of both traditional NSAIDs and existing cox-2 inhibitors, the researchers said.

"Ultimately, through the dissection of these intricate pathways, it may be possible to identify drugs that provide all the therapeutic effects of NSAIDs and cox-2-selective inhibitors but lack their adverse side effects," added Matthew Breyer of Vanderbilt University Medical School in an accompanying preview. "Until that time, one can only marvel at the combination of therapeutic and cardioprotective effects of nature’s own compound, salicylate, and its chemically modified derivative, aspirin."

Heidi Hardman | EurekAlert!
Further information:
http://www.cellmetabolism.org

More articles from Life Sciences:

nachricht BigH1 -- The key histone for male fertility
14.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Guardians of the Gate
14.12.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>