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Diclofenac

Diclofenac (marketed as Voltaren®, Voltarol®, Diclon® and Cataflam®) is a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation, such as in arthritis or acute injury. It can also be used to reduce menstrual pain. more...

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Voltaren and Voltarol contain the sodium salt of diclofenac. In the United Kingdom Voltarol can be supplied with either the sodium salt or potassium salt, while Cataflam in some other countries is the potassium salt only. Diclofenac is available in stomach acid resistant formulations (25 and 50 mg), fast disintegrating oral formulations (50 mg), slow- and controlled-release forms (75, 100 or 150 mg), suppositories (50 and 100 mg), and injectable forms (50 and 75 mg). Diclofenac is also available over the counter (OTC) in some countries: Voltaren® dolo (12.5 mg diclofenac as potassium salt) in Switzerland and Germany, and preparations with 25 mg diclofenac are OTC in New Zealand. OTC use is approved for minor aches and pains and fever associated with common infections.

Diclofenac is available as a generic drug in a number of formulations.

Mechanism of action

The exact mechanism of action is not entirely known, but it is thought that the primary mechanism responsible for its anti-inflammatory/antipyretic/analgesic action is inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX).

Diclofenac, it seems, may also be a unique member of the NSAIDs. There is some evidence that diclofenac inhibits the lipooxygenase pathways, thus reducing formation of the leukotrienes (also pro-inflammatory autacoids). There is also speculation that diclofenac may inhibit phospholipase A₂ as part of its mechanism of action. These additional actions may explain the high potency of diclofenac - it is the most potent NSAID on a molar basis.

Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid. This is also the main side effect of diclofenac. Diclofenac has a low to moderate preference to block the COX2-isoenzyme (approximately 10-fold) and is said to have therefore a somewhat lower incidence of gastrointestinal complaints than noted with indomethacin and aspirin.

The action of one single dose is much longer (6 to 8 hours) than the very short half-life of the drug indicates. This could partly be due to a particular high concentration achieved in synovial fluids.

Common uses

Diclofenac is used for musculoskeletal complaints, especially arthritis (rheumatoid arthritis, osteoarthritis, spondylarthritis, ankylosing spondylitis), gout attacks, and pain management in case of kidney stones and gallstones. An additional indication is the treatment of acute migraines. Diclofenac is used commonly to treat mild to moderate post-operative or post-traumatic pain, particular when inflammation is also present, and is effective against menstrual pain.

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Vultures: canaries in the coal mine?
From Environment, 4/1/04

An anti-inflammatory prescribed to domestic livestock may be at the heart of a catastrophic population crash of three South Asian vulture species, scientists report. In the last decade. South Asia's Oriental white-backed vultures (Gyps bengalensis), long-billed vultures (Gyps indicus), and slender-billed vultures (Gyps tenuirostris) have suffered population losses of more than 95 percent. An international team of scientists assembled by The Peregrine Fund in Boise, Idaho, conducted a three-year investigation of the drastic decline. Their results were unexpected: Early examinations revealed that the vultures were dying from kidney failure, which the scientists suspected was caused by an environmental toxin. However, after samples tested negative for pesticides, heavy metals, and other toxins, the team began investigating less conventional possibilities. Turning their focus toward pharmaceuticals used to treat livestock, the scientists discovered that the drug diclofenac was responsible for the deaths. Diclofenac, a nonsteroidal anti-inflammatory, has been prescribed to humans for pain and inflammation for decades. In South Asia, the veterinary use of diclofenac to treat lame or feverish animals has grown in the past decade and is now widespread. Livestock that die shortly after being treated with the drug contain enough residues to cause kidney failure as well as death in vultures that consume the carcasses, the tests revealed. "This discovery is significant in that it is the first known case of a pharmaceutical causing major ecological damage over a huge geographic area and threatening three species with extinction," says project leader J. Lindsay Oaks, an assistant professor of veterinary medicine at Washington State University. According to The Peregrine Fund, in this case vultures are the canary in the coal miner's cage, warning of a potentially dangerous environmental health hazard. "Finding that a drug is responsible for the collapse and threatened extinction of these species is helpful yet alarming," says Rick Watson, International Programs Director with The Peregrine Fund. "Helpful, because now we can do something about it, and we may have time to save these species. Alarming, because this may not be the only pharmaceutical impacting wildlife," he says. In a statement endorsed by seven conservation groups, the researchers call upon the manufacturers of diclofenac and governments in Asia, Africa, Europe, and the Middle East to ban the veterinary use of the drug in the threatened vultures' habitat.

[ILLUSTRATION OMITTED]

--The New York Times, 29 January: The Peregrine Fund press release. 28 January; and http://www.peregrinefund.org/press/Vulture_diclofenac_manifesto.html. (S.B.)

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