Diclofenac, sold under the trade names Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or applied to the skin. Improvements in pain typically occur within half an hour and last for as much as eight hours. It is also available in combination with misoprostol in an effort to decrease stomach problems.
Diclofenac was patented in 1965 by Ciba-Geigy and came into medical use in the United States in 1988. It is available as a generic medication. In the United States the wholesale cost per dose is less than US$0.15 as of 2018. In 2016 it was the 78th most prescribed medication in the United States with more than 9 million prescriptions. It is available as both a sodium and a potassium salt.
In many countries, eye drops are sold to treat acute and chronic nonbacterial inflammation of the anterior part of the eyes (e.g., postoperative states). Diclofenac eye drops have also been used to manage pain for traumatic corneal abrasion.
Diclofenac consumption has been associated with significantly increased vascular and coronary risk in a study including coxib, diclofenac, ibuprofen and naproxen. Upper gastrointestinal complications were also reported. Major adverse cardiovascular events (MACE) were increased by about a third by diclofenac, chiefly due to an increase in major coronary events. Compared with placebo, of 1000 patients allocated to diclofenac for a year, three more had major vascular events, one of which was fatal. Vascular death was increased significantly by diclofenac.
A subsequent large study of 74,838 Danish users of NSAIDs or coxibs found no additional cardiovascular risk from diclofenac use. A very large study of 1,028,437 Danish users of various NSAIDs or coxibs found the "Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk.
The primary mechanism responsible for its anti-inflammatory, antipyretic, and analgesic action is thought to be inhibition of prostaglandin synthesis by inhibition of the transiently expressed prostaglandin-endoperoxide synthase-2 (PGES-2) also known as cycloxygenase-2 (COX-2). It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.
Diclofenac may also be a unique member of the NSAIDs. Some evidence indicates it inhibits the lipoxygenase pathways, thus reducing formation of the leukotrienes (also pro-inflammatory autacoids). It also may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain its high potency - it is the most potent NSAID on a broad basis.
"The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian Subcontinent that pose a potential threat to human health. In many places, populations of feral dogs (Canis familiaris) have increased sharply from the disappearance of Gyps vultures as the main scavenger of wild and domestic ungulate carcasses. Associated with the rise in dog numbers is an increased risk of rabies" and casualties of almost 50,000 people. The Government of India cites this as one of the major consequences of a vulture species extinction. A major shift in the transfer of corpse pathogens from vultures to feral dogs and rats could lead to a disease pandemic, causing millions of deaths in a crowded country like India, whereas vultures' digestive systems safely destroy many species of such pathogens. Vultures are long-lived and slow to breed. They start breeding only at the age of six and only 50% of young survive. Even if the government ban is fully implemented, it will take several years to revive the vulture population.