48-798: See text. The Gypaetinae is one of two subfamilies of Old World vultures the other being the Aegypiinae . Some taxonomic authorities place the Gypaetinae within the Perninae hawks. They are presently found throughout much of Africa, Asia, and southern Europe, hence being considered "Old World" vultures, but as recently as the Late Pleistocene , they were also present in North America . A 2005 study found Eutriorchis astur to be closely related. Genera known only from fossils include: (sometimes placed in
96-711: 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 their young survive. Even if the government ban is fully implemented, it will take many years to revive the vulture population. The loss of vultures has had a social impact on the Indian Zoroastrian Parsi community , who traditionally use vultures to dispose of human corpses in Towers of Silence , but are now compelled to seek alternative methods of disposal. Despite
144-469: A meta-analysis of papers and reports up to April 2006 suggesting a relative increased rate of heart disease of 1.63 compared to nonusers. Professor Peter Weissberg, medical director of the British Heart Foundation said, "However, the increased risk is small, and many patients with chronic debilitating pain may well feel that this small risk is worth taking to relieve their symptoms". Only aspirin
192-449: A more detrimental effect on vulture populations than larger, infrequent events because population recovery is more successful when there is a longer time between poisonings. To increase populations, vultures can be reintroduced to poison-free protected areas near other groups of vultures to keep the populations high. This will make it easier for vultures to maintain some individuals after a poisoning event. A project named "Vulture Restaurant"
240-463: A prescription. Use of diclofenac for animals is controversial due to toxicity when eaten by scavenging birds that eat dead animals; the medication has been banned for veterinary use in several countries. Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent – a 95% decline by 2003 and a 99.9% decline by 2008. The mechanism
288-416: A study including coxib, diclofenac, ibuprofen and naproxen . Upper gastrointestinal complications were also reported. Major adverse cardiovascular events 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
336-399: A year, three more had major vascular events, one of which was fatal. Vascular death was increased by diclofenac (1·65). Following the identification of increased risks of heart attacks with the selective COX-2 inhibitor rofecoxib in 2004, attention has focused on all the other members of the nonsteroidal anti-inflammatory drug group, including diclofenac. Research results are mixed, with
384-464: A year. Vulture heads are believed to provide clairvoyance or good luck like winning the lottery. The length of time a vulture can be used by healers is dependent on size and species. Some healers have been recorded using Cape vultures for 6 years because they are said to last longer than other species. Others use 1-2 individuals a year but this rate is unsustainable given the estimated number of healers. In Southern Africa , traditional medicine
432-494: Is a major health threat. India has one of the world's highest incidences of rabies. For communities such as the Parsi , who practice sky burials in which human corpses are put on the top of a Tower of Silence , vulture population declines can have serious cultural implications. Conservation efforts would be most effective in large, protected areas because vultures are most populous in those. Small but frequent poisoning events have
480-483: Is a semi-bald head , sometimes without feathers or with just simple down. Historically, it was thought that this was due to feeding habits, as feathers would be glued with decaying flesh and blood. However, more recent studies have shown that it is actually a thermoregulatory adaptation to avoid facial overheating; the presence or absence of complex feathers seems to matter little in feeding habits, as some vultures are quite raptorial. † = extinct More than half of
528-446: Is called Muthi . For some healers it is believed to cure illnesses, while others believe it cures curses. Vulture muthi involves separate body parts being dried, burned, or ground up. The results may be consumed by mixing with food, drinking, snorting, or applying to cuts. Some healers look for signs of poisoning when purchasing vultures, but others are unaware of how to do this and are at risk of poisoning their clients. Another part of
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#1732869509658576-558: Is increased significantly by diclofenac. In October 2020, the US Food and Drug Administration (FDA) required the prescription label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in fetuses that result in low amniotic fluid. In 2013, a study found major vascular events were increased by about a third by diclofenac, chiefly due to an increase in major coronary events. Compared with placebo, of 1000 people allocated to diclofenac for
624-507: Is not recommended in the third trimester of pregnancy . It is likely safe during breastfeeding . Diclofenac is believed to work by decreasing the production of prostaglandins , like other drugs in this class. In 2022, it was the 51st most commonly prescribed medication in the United States, with more than 12 million prescriptions. It is available as its acid or in two salts, as either diclofenac sodium or potassium. Diclofenac
672-438: Is one of the most prevalent threats to vulture populations. Diclofenac#Ecological effects Diclofenac , sold under the brand name Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout . It can be taken orally (swallowed by mouth), inserted rectally as a suppository , injected intramuscularly , injected intravenously , applied to
720-618: Is presumed to be kidney failure ; however, toxicity may be due to direct inhibition of uric acid secretion in vultures. Vultures eat the carcasses of livestock that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical, as vultures do not have a particular enzyme to break down diclofenac. At a meeting of the National Wildlife Board in March 2005, the Government of India announced it intended to phase out
768-661: Is the most potent NSAID on a broad basis. Marked differences exist among nonsteroidal anti-inflammatory drugs in their selective inhibition of the two subtypes of cyclooxygenase, COX-1, and COX-2. Drug developers have focused on selective COX-2 inhibition, particularly as a way to minimize the gastrointestinal side effects of nonsteroidal anti-inflammatory drugs. In practice, the use of some COX-2 inhibitors with their adverse effects has led to massive numbers of lawsuits alleging wrongful death by heart attack , yet other significantly COX-selective nonsteroidal anti-inflammatory drugs, such as diclofenac, have been well tolerated by most of
816-728: Is underway in Nepal in an effort to conserve the dwindling number of vultures. The "restaurant" is an open grassy area where naturally dying, sick, and old cows are fed to the vultures. Organizations across Africa are working to reduce threats to vulture species with efforts to change and create policies to protect species both at the national and international scale. Proposed strategies to reduce poisoning events include mobile phone numbers to report offenders, campaigns to educate about poisoning risks to humans, and improving response speed to poisoning events. Poison response training would be an important implementation in conservation efforts because this
864-496: Is used to treat pain related to arthritis , dysmenorrhea , rheumatic diseases and other inflammatory disorders , kidney stones and gallstones . An additional indication is the treatment of acute migraines . Diclofenac is used to treat mild to moderate postoperative or post-traumatic pain, in particular when inflammation is also present. Diclofenac ophthalmic is indicated for the treatment of postoperative inflammation in people who have undergone cataract extraction and for
912-556: The Aegypiinae ) (sometimes placed in the Aegypiinae ) Old World vultures Old World vultures are vultures that are found in the Old World , i.e. the continents of Europe, Asia and Africa, and which belong to the family Accipitridae , which also includes eagles , buzzards , kites , and hawks . Old World vultures are not closely related to the superficially similar New World vultures and condors , and do not share that group's good sense of smell. The similarities between
960-831: The African vulture trade is use for bushmeat consumption. Collisions with electrical infrastructure account for roughly 9% of vulture deaths in Africa. Some organizations in South Africa are working with power companies to mitigate this threat. As vultures play an important role in ecosystems, their population decline can have cultural, public health, and economic implications for communities. The decline in vultures has led to hygiene problems in India as carcasses of dead animals now tend to rot, or be eaten by rats or feral dogs , rather than be consumed by vultures. Rabies among these other scavengers
1008-408: The turkey vulture , can tolerate at least 100 times the level of diclofenac that is lethal to Gyps species. "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 have increased sharply from the disappearance of Gyps vultures as
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#17328695096581056-505: 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." Diclofenac is similar in COX-2 selectivity to celecoxib . As with other nonsteroidal anti-inflammatory drugs,
1104-569: The Old World vulture species are listed as vulnerable , endangered , or critically endangered by the IUCN Red List . Population declines are caused by a variety of threats that vary by species and region, with most notable declines in Asia due to diclofenac use. Within Africa, a combination of poisonings and vulture trade (including use as bushmeat and traditional medicine) account for roughly 90% of
1152-507: The United States, 1% diclofenac gel was approved by the FDA in 2007 as a prescription drug for the temporary relief of the pain of osteoarthritis of joints in the hands, knees, and feet. In 2020, the FDA approved the gel formulation for nonprescription use. In January 2015, diclofenac oral preparations were reclassified as prescription-only medicines in the UK. The topical preparations are available without
1200-572: The anterior part of the eyes (such as postoperative states). The eye drops have also been used to manage pain for traumatic corneal abrasion . Diclofenac is often used to treat chronic pain associated with cancer , especially if inflammation is present. Diclofenac is contraindicated for pregnant women; for people with active stomach and/or duodenal ulceration or gastrointestinal bleeding ; and for people undergoing coronary artery bypass surgery . Diclofenac consumption has been associated with significantly increased vascular and coronary risk in
1248-459: The drug in India can result in jail time. But while the Government of India banned diclofenac, over a year later, in 2007, it continued to be sold and remains a problem in other parts of the world. Poisoning accounts for a majority of vulture deaths in Africa. Ivory poachers poison carcasses with the intent of killing vultures, since vultures circling over a carcass alert authorities to a kill. An increase in demand for ivory has both increased
1296-550: The gills, kidneys and liver. Diclofenac is used for livestock; such use was responsible for the Indian vulture crisis , during which in a few years 95% of the country's vulture population was killed, and in many countries, agricultural use is now forbidden. Diclofenac is approved as a veterinary medication in some countries for the treatment of pets as well as in livestock. In some species of birds, diclofenac causes accumulation of uric acid crystals in internal organs—especially
1344-793: The land for longer, but, if the ill animals die, their carcasses contain diclofenac. Farmers leave the dead animals out in the open, relying on vultures to tidy up. Diclofenac present in carcass flesh is eaten by vultures, which are sensitive to diclofenac, and they suffer kidney failure, visceral gout , and death as a result of diclofenac poisoning . The drug is poisonous enough that only a small amount of animal carcases need to contain it to have detrimental effects on vulture populations. Meloxicam (another NSAID) has been found to be harmless to vultures and should prove an acceptable alternative to diclofenac. Bans on diclofenac in veterinary practices have been implemented in Pakistan and Nepal and selling or using
1392-729: The latter are closely related and possibly even synonymous with Aquilinae . Within Aegypiinae, Torgos , Aegypius , Sarcogyps and Trigonoceps are particularly closely related and possibly within the same genus. Despite the name of the group, "Old World" vultures were widespread in North America until relatively recently, until the end of the Late Pleistocene epoch around 11,000 years ago. Both Old World and New World vultures are scavenging birds , feeding mostly from carcasses of dead animals . Old World vultures find carcasses exclusively by sight. A particular characteristic of many vultures
1440-430: 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
1488-734: The number of deaths would be quite small. A paper published in 2021 identified the first authenticated death of a vulture from diclofenac in Spain, a cinereous vulture . Diclofenac is on the European Union's watch list because it pollutes the Baltic Sea. When the substance enters freshwater, it has an environmental impact and is considered more difficult to remove in wastewater treatment plants than, for example, ibuprofen. Harmful residues have been found in blue mussels and fish, among others, where it has been found to cause damage to internal organs such as
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1536-420: The population declines. And because vultures are scavengers , their population decline can have cultural, public health, and economic implications for communities and be even more problematic than the decline of other endangered species. Vulture populations are particularly vulnerable because they typically feed in large groups and easily fall victim to mass poisoning events. Diclofenac poisoning has caused
1584-484: The population. Besides the COX-inhibition, several other molecular targets of diclofenac possibly contributing to its pain-relieving actions have recently been identified. These include: The duration of action (i.e., duration of pain relief) of a single dose is longer (6 to 8 h ) than the drug's 1.2–2 h half-life. This could be partly because it persists for over 11 hours in synovial fluids . Diclofenac
1632-498: The primary mechanism responsible for its anti-inflammatory , antipyretic and analgesic action is thought to be inhibition of prostaglandin synthesis through COX -inhibition. The main target in the inhibition of prostaglandin synthesis appears to be the transiently expressed prostaglandin-endoperoxide synthase-2 (PGES-2), also known as cycloxygenase-2 (COX-2). That is, diclofenac is partially selective for COX-2. The reported selectivity for COX-2 varies from 1.5 to 30 depending on
1680-412: The rate of elephant poachings as well as increased the rate at which vultures are killed off by consuming the poisoned elephant remains. In Kruger National Park , white-backed vultures will be eradicated in the next 60 years if poisoned carcasses are not detected and neutralized. Eliminating carcass poisoning is challenging because it is far easier to carry out than to regulate. Park officials often lack
1728-446: The skin topically , or through eye drops . Improvements in pain last up to eight hours. It is also available as the fixed-dose combination diclofenac/misoprostol (Arthrotec) to help protect the stomach. Common side effects include abdominal pain , gastrointestinal bleeding , nausea, dizziness, headache, and swelling. Serious side effects may include heart disease , stroke , kidney problems , and stomach ulceration . Use
1776-565: The sodium salt of diclofenac. In the United Kingdom, Voltarol can be supplied with either the sodium salt or the potassium salt, while Cataflam, sold in some other countries, is the potassium salt only. However, Voltarol Emulgel contains diclofenac diethylammonium 1.16%, being equivalent to 1% sodium salt. In 2016, Voltarol was one of the biggest selling branded over-the-counter medications sold in Great Britain, with sales of £39.3 million. In
1824-422: The source. The drug may be bacteriostatic via inhibiting bacterial DNA synthesis. Diclofenac has a relatively high lipid solubility, making it one of the few nonsteroidal anti-inflammatory drugs that are able to enter the brain by crossing the blood-brain barrier . As in the rest of the body, it is thought to exert its effect in the brain through inhibition of COX-2. In addition, it may have effects inside
1872-414: The spinal cord. Diclofenac may be a unique member of the nonsteroidal anti-inflammatory drugs in other aspects. Some evidence indicates it inhibits the lipoxygenase pathways, thus reducing the formation of leukotrienes (also pro-inflammatory autacoids ). It also may inhibit phospholipase A2 , which may be relevant to its mechanism of action. These additional actions may explain its high potency – it
1920-451: The temporary relief of pain and photophobia in people undergoing corneal refractive surgery. Diclofenac is also available in topical forms and is useful for osteoarthritis but not other types of long-term musculoskeletal pain. Diclofenac may also help with actinic keratosis and with acute pain caused by minor strains, sprains and contusions . In many countries, eye drops are sold to treat acute and chronic nonbacterial inflammation of
1968-448: The training to identify toxic chemicals before it is too late and calling on average community members to turn in perpetrators reports is challenging if financial incentives to do so are insufficient. Vultures are also unintentionally poisoned when they consume carcasses of predators that have been poisoned by livestock farmers. For those who rely on livestock to make a living, illegal pesticides are often used on fruits, meats, or even
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2016-712: The two groups of vultures are due to convergent evolution , rather than a close relationship. They were widespread in both the Old World and North America during the Neogene . Old World vultures are probably a polyphyletic group within Accipitridae, belonging to two separate not closely related groups within the family. Most authorities refer to two major clades: Gypaetinae ( Gypaetus , Gypohierax and Neophron ) and Aegypiinae ( Aegypius , Gyps , Sarcogyps , Torgos , Trigonoceps and possibly Necrosyrtes ). The former seem to be nested with Perninae hawks, while
2064-501: The veterinary use of diclofenac. Meloxicam is a safer alternative to replace use of diclofenac. It is more expensive than diclofenac, but the cost is dropping as more pharmaceutical companies are beginning to manufacture it. Steppe eagles have the same vulnerability to diclofenac as Old World vultures and are therefore at a similar risk from its effects. Diclofenac has been shown also to harm freshwater fish species such as rainbow trout. In contrast, New World vultures , such as
2112-539: The vulture crisis, diclofenac remains available in other countries including many in Europe. It was controversially approved for veterinary use in Spain in 2013 and continues to be available, despite Spain being home to around 90% of the European vulture population and an independent simulation showing that the drug could reduce the population of vultures by 1–8% annually. Spain's medicine agency presented simulations suggesting that
2160-521: The vulture population in India and Pakistan to decline by up to 99% , and two or three species of vulture in South Asia are nearing extinction. This has been caused by the practice of medicating working farm animals with diclofenac, which is a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and pain-killing actions. Diclofenac administration keeps animals that are ill or in pain working on
2208-604: The water in a wateringhole in order to eliminate large predators that threaten their livestock. Agricultural poisoning is relatively easy as it does not require specific skills and the poison is cheap with a long shelf life. Vultures in Africa are killed for use in traditional medicine as part of the African vulture trade . Vultures can be targeted for the industry directly or collected from other poisoning events, but close to 30% of vulture deaths recorded in Africa can be tied back to belief-based use. In South Africa , vulture consumption events have been estimated to occur 59,000 times
2256-557: Was first synthesized by Alfred Sallmann and Rudolf Pfister in 1973. The name "diclofenac" derives from its chemical name: 2-(2,6- dichlo ranilino) phen yl ac etic acid. It was patented in Germany in 1978 by Ciba-Geigy (now Novartis ). It came into medical use in the United States in 1988. GlaxoSmithKline purchased the rights in 2015. It is available as a generic medication . Diclofenac formulations are available worldwide under many different brand names. Voltaren and Voltarol contain
2304-622: Was found not to increase the risk of heart disease; however, this is known to have a higher rate of gastric ulceration than diclofenac. As of January 2015, the MHRA announced that diclofenac would be reclassified as a prescription-only medicine (POM) due to the risk of cardiovascular adverse events. A subsequent large study of 74,838 Danish users of nonsteroidal anti-inflammatory drugs or coxibs found no additional cardiovascular risk from diclofenac use. A very large study of 1,028,437 Danish users of various nonsteroidal anti-inflammatory drugs or coxibs found
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