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Non-steroidal anti-inflammatory drugs ( NSAID) are members of a therapeutic which , decreases inflammation, , and . Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of , , and . The most prominent NSAIDs are , , and , all available over the counter (OTC) in most countries. (acetaminophen) is generally not considered an NSAID because it has only minor anti-inflammatory activity.

(1998). 9788481743401, España. .

The term non-steroidal, common from around 1960, distinguishes these drugs from , another class of anti-inflammatory drugs, which during the 1950s had acquired a bad reputation due to overuse and side-effect problems after their introduction in 1948.

NSAIDs work by inhibiting the activity of (the COX-1 and COX-2 ). In cells, these enzymes are involved in the synthesis of key biological mediators, namely , which are involved in , and , which are involved in .

There are two general types of NSAIDs available: non-selective and COX-2 selective. Most NSAIDs are non-selective, and inhibit the activity of both COX-1 and COX-2. These NSAIDs, while reducing inflammation, also inhibit platelet aggregation and increase the risk of gastrointestinal ulcers and bleeds. COX-2 selective inhibitors have fewer gastrointestinal side effects, but promote , and some of these agents substantially increase the risk of . As a result, certain COX-2 selective inhibitors—such as —are no longer used due to the high risk of undiagnosed . These differential effects are due to the different roles and tissue localisations of each COX isoenzyme. By inhibiting physiological COX activity, NSAIDs may cause deleterious effects on kidney function, and, perhaps as a result of water and sodium retention and decreases in renal blood flow, may lead to heart problems. In addition, NSAIDs can blunt the production of , resulting in , since haemoglobin needs this hormone to be produced.

Medical uses
NSAIDs are often suggested for the treatment of acute or chronic conditions where and inflammation are present. NSAIDs are generally used for the symptomatic relief of the following conditions:
(2026). 9780975791929, Australian Medicines Handbook Pty Ltd.

Chronic pain and cancer-related pain
The effectiveness of NSAIDs for treating non-cancer chronic pain and cancer-related pain in children and adolescents is not clear. There have not been sufficient numbers of high-quality randomised controlled trials conducted.

Inflammation
Differences in anti-inflammatory activity between the various individual NSAIDs are small, but there is considerable variation among individual patients in therapeutic response and tolerance to these drugs. About 60% of patients will respond to any NSAID; of the others, those who do not respond to one may well respond to another. Pain relief starts soon after taking the first dose, and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to three weeks. If appropriate responses are not obtained within these times, another NSAID should be tried.

Surgical pain
Pain following can be significant, and many people require strong pain medications such as opioids. There is some low-certainty evidence that starting NSAID painkiller medications in adults early, before surgery, may help reduce post-operative pain, and also reduce the dose or quantity of opioid medications required after surgery. Any increased risk of surgical bleeding, bleeding in the gastrointestinal system, myocardial infarctions, or injury to the kidneys has not been well studied. When used in combination with paracetamol, the analgesic effect on post-operative pain may be improved.

Aspirin
, the only NSAID able to irreversibly inhibit COX-1, is also indicated for through inhibition of platelet aggregation. This is useful for the management of arterial , and prevention of adverse cardiovascular events like heart attacks. Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane A2.
(2026). 9783804728981, Wissenschaftliche Verlagsgesellschaft Stuttgart.

Dentistry
NSAIDs are useful in the management of post-operative following invasive dental procedures such as dental extraction. When not contra-indicated, they are favoured over the use of alone due to the anti-inflammatory effect they provide. There is weak evidence suggesting that taking pre-operative analgesia can reduce the length of post operative pain associated with placing orthodontic spacers under local anaesthetic.

Alzheimer's disease
Based on observational studies and randomized controlled trials, NSAID use is not effective for the treatment or prevention of Alzheimer's disease.

Contraindications
NSAIDs may be used with caution by people with the following conditions:
  • Persons who are over age 50, and who have a family history of gastrointestinal (GI) problems
  • Persons who have had previous gastrointestinal problems from NSAID use

NSAIDs should usually be avoided by people with the following conditions:

  • Peptic ulcer or stomach bleeding
  • Uncontrolled
  • People with inflammatory bowel disease
  • Past transient ischemic attack (excluding )
  • Past (excluding )
  • Past myocardial infarction (excluding )
  • Coronary artery disease (excluding )
  • Undergoing coronary artery bypass surgery
  • Congestive heart failure (excluding low-dose aspirin)
  • In third trimester of pregnancy
  • Persons who have undergone gastric bypass surgery
  • Persons who have a history of allergic or allergic-like NSAID hypersensitivity reactions, e.g., aspirin-exacerbated respiratory disease

Adverse effects
The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly common. Use of NSAIDs increases the risk of a range of gastrointestinal (GI) problems, kidney disease, and adverse cardiovascular events. As commonly used for post-operative pain, there is evidence of increased risk of kidney complications. Their use following gastrointestinal surgery remains controversial, given mixed evidence of increased risk of leakage from any bowel created.

An estimated 10–20% of people taking NSAIDs experience . In the 1990s, high doses of prescription NSAIDs were associated with serious upper gastrointestinal adverse events, including bleeding.

NSAIDs, like all medications, may interact with other medications. For example, concurrent use of NSAIDs and quinolone antibiotics may increase the risk of the adverse central nervous system effects of quinolones including seizure.

(2026). 9780853698456, BMJ Group and RPS Publishing.

There is an argument over the benefits and risks of NSAIDs for treating chronic musculoskeletal pain. Each drug has a benefit-risk profile, and balancing the risk of no treatment with the competing potential risks of various therapies should be considered. For people over the age of 65 years old, the balance between the benefits of pain-relief medications such as NSAIDs and the potential for adverse effects has not been well determined.

There is some evidence suggesting that, for some people, use of NSAIDs (or other anti-inflammatories) may contribute to the initiation of chronic pain.

Side effects are dose-dependent, and in many cases, severe enough to pose the risk of ulcer perforation, upper gastrointestinal bleeding, and death, limiting the use of NSAID therapy. An estimated 10–20% of NSAID patients experience , and NSAID-associated upper gastrointestinal adverse events are estimated to result in 103,000 hospitalizations and 16,500 deaths per year in the United States, and represent 43% of drug-related emergency visits. Many of these events are avoidable; a review of physician visits and prescriptions estimated that unnecessary prescriptions for NSAIDs were written in 42% of visits.

Aspirin should not be taken by people who have salicylate intolerance or a more generalized to NSAIDs, and caution should be exercised in those with or -precipitated . Owing to its effect on the stomach lining, manufacturers recommend people with , mild , or seek medical advice before using aspirin.

(1985). 9780195036343, Oxford University Press. .
Use of aspirin during is not recommended owing to increased bleeding tendency. People with , , or should not take aspirin because it inhibits the ability of the kidneys to excrete , and thus may exacerbate these conditions.

Combinational risk
If a COX-2 inhibitor is taken, a traditional NSAID (prescription or over-the-counter) should not be taken at the same time.

(Vioxx) was shown to produce significantly fewer gastrointestinal adverse drug reactions (ADRs) compared with naproxen. The study, the VIGOR trial, raised the issue of the cardiovascular safety of the coxibs (COX-2 inhibitors). A statistically significant increase in the incidence of myocardial infarctions was observed in patients on rofecoxib. Further data, from the APPROVe trial, showed a statistically significant relative risk of cardiovascular events of 1.97 versus placebo—which caused a worldwide withdrawal of rofecoxib in October 2004.

Use of methotrexate together with NSAIDs in rheumatoid arthritis is safe if adequate monitoring is done.

Cardiovascular
NSAIDs, aside from aspirin, increase the risk of myocardial infarction and . This occurs at least within a week of use. They are not recommended in those who have had a previous heart attack as they increase the risk of death or recurrent MI. Evidence indicates that may be the least harmful out of these.

NSAIDs, aside from (low-dose) aspirin, are associated with a doubled risk of in people without a history of cardiac disease. In people with such a history, use of NSAIDs (aside from low-dose aspirin) was associated with a more than 10-fold increase in heart failure. If this link is proven causal, researchers estimate that NSAIDs would be responsible for up to 20 percent of hospital admissions for congestive heart failure. In people with heart failure, NSAIDs increase mortality risk () by approximately 1.2–1.3 for naproxen and ibuprofen, 1.7 for rofecoxib and celecoxib, and 2.1 for diclofenac.

On 9 July 2015, the Food and Drug Administration (FDA) toughened warnings of increased and risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs) other than .

Possible erectile dysfunction risk
A 2005 Finnish survey study found an association between long-term (over three months) use of NSAIDs and erectile dysfunction.

A 2011 publication in The Journal of Urology received widespread publicity. According to the study, men who used NSAIDs regularly were at significantly increased risk of erectile dysfunction. A link between NSAID use and erectile dysfunction still existed after controlling for several conditions. However, the study was observational and not controlled, with a low original participation rate, potential participation bias, and other uncontrolled factors. The authors warned against drawing any conclusions regarding cause.

Gastrointestinal
The main adverse drug reactions (ADRs) associated with NSAID use relate to direct and indirect irritation of the gastrointestinal (GI) tract. NSAIDs cause a dual assault on the GI tract: the acidic molecules directly irritate the , and inhibition of COX-1 and COX-2 reduces the levels of protective . Inhibition of prostaglandin synthesis in the GI tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished mucus secretion and diminished trophic effects on the epithelial mucosa.

Common gastrointestinal side effects include:

Clinical NSAID ulcers are related to the systemic effects of NSAID administration. Such damage occurs irrespective of the route of administration of the NSAID (e.g., oral, rectal, or parenteral) and can occur even in people who have .Textbook of Gastroenterology, Tadataka Yamada, 2008, Ch.40, Peptic Ulcer Disease, page 941

Ulceration risk increases with therapy duration and with higher doses. To minimize GI side effects, it is prudent to use the lowest effective dose for the shortest period—a practice that studies show is often not followed. Over 50% of patients who take NSAIDs have sustained some mucosal damage to their small intestine.

The risk and rate of gastric adverse effects are different depending on the type of NSAID medication a person is taking. , , and use appears to lead to the highest rate of gastric adverse effects, while (lower doses) and appear to have lower rates.

Certain NSAIDs, such as aspirin, have been marketed in formulations that manufacturers claim reduce the incidence of gastrointestinal ADRs. Similarly, some believe that rectal formulations may reduce gastrointestinal ADRs. However, consistent with the systemic mechanism of such ADRs, and in clinical practice, these formulations have not demonstrated a reduced risk of GI ulceration.

Numerous "gastro-protective" drugs have been developed to prevent gastrointestinal toxicity in people who need to take NSAIDs regularly. Gastric adverse effects may be reduced by taking medications that suppress acid production such as proton pump inhibitors (e.g.: and ), or by treatment with a drug that mimics to restore the lining of the GI tract (e.g.: a prostaglandin analog ). Diarrhea is a common side effect of misoprostol; however, higher doses of misoprostol have been shown to reduce the risk of a person having a complication related to a gastric ulcer while taking NSAIDs. While these techniques may be effective, they are expensive for maintenance therapy.

NSAID hybrids prevent the gastric ulceration/bleeding associated with taking the NSAIDs alone. Hydrogen sulfide is known to have a protective effect on the cardiovascular and gastrointestinal system.

Inflammatory bowel disease
NSAIDs should be used with caution in individuals with inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) due to their tendency to cause gastric bleeding and form ulceration in the gastric lining.

Renal
NSAIDs are also associated with a fairly high incidence of adverse drug reactions (ADRs) on the kidney and over time can lead to chronic kidney disease. The mechanism of these kidney ADRs is due to changes in kidney blood flow. Prostaglandins normally dilate the afferent arterioles of the glomeruli. This helps maintain normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of . This is particularly important in kidney failure, where the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II levels. At these elevated levels, angiotensin II also constricts the afferent arteriole into the glomerulus in addition to the efferent arteriole it normally constricts. Since NSAIDs block this prostaglandin-mediated effect of afferent arteriole dilation, particularly in kidney failure, NSAIDs cause unopposed constriction of the afferent arteriole and decreased RPF (renal perfusion flow) and GFR.

Common ADRs associated with altered kidney function include:

  • Sodium and fluid retention
  • (high blood pressure)

These agents may also cause kidney impairment, especially in combination with other nephrotoxic agents. Kidney failure is especially a risk if the patient is also concomitantly taking an (which removes angiotensin II's vasoconstriction of the efferent arteriole) and a (which drops plasma volume, and thereby RPF)—the so-called "triple whammy" effect.

In rarer instances NSAIDs may also cause more severe kidney conditions:

  • Interstitial nephritis
  • Nephrotic syndrome
  • Acute kidney injury
  • Acute tubular necrosis
  • Renal papillary necrosis

NSAIDs in combination with excessive use of or (acetaminophen) may lead to analgesic nephropathy.

Photosensitivity
is a commonly overlooked adverse effect of many of the NSAIDs. The 2-arylpropionic acids are the most likely to produce photosensitivity reactions, but other NSAIDs have also been implicated including , , and .

, since withdrawn due to its , was the most photoactive NSAID observed. The mechanism of photosensitivity, responsible for the high photoactivity of the 2-arylpropionic acids, is the ready of the . The specific absorbance characteristics of the different 2-aryl substituents, affects the decarboxylation mechanism.

During pregnancy
While NSAIDs as a class are not direct , use of NSAIDs in late pregnancy can cause premature closure of the fetal ductus arteriosus and kidney ADRs in the fetus. Thus, NSAIDs are not recommended during the third trimester of pregnancy because of the increased risk of premature constriction of the ductus arteriosus. Additionally, they are linked with and . Aspirin, however, is used together with in pregnant women with antiphospholipid syndrome. Additionally, can be used in pregnancy to treat by reducing fetal urine production via inhibiting fetal renal blood flow.

In contrast, (acetaminophen) is regarded as being safe and well tolerated during pregnancy, but Leffers et al. released a study in 2010, indicating that there may be associated male infertility in the unborn. Doses should be taken as prescribed, due to risk of liver toxicity with overdoses.

In France, the country's health agency contraindicates the use of NSAIDs, including aspirin, after the sixth month of pregnancy.

In October 2020, the U.S. Food and Drug Administration (FDA) required the prescribing information to be updated for all nonsteroidal anti-inflammatory medications, to describe the risk of kidney problems in unborn babies which can then lead to low amniotic fluid levels, as a result of the use of NSAIDs. They are recommending avoiding the use of NSAIDs by pregnant women at 20 weeks or later in pregnancy.

Allergy and allergy-like hypersensitivity reactions
A variety of allergic or allergic-like NSAID hypersensitivity reactions follow the ingestion of NSAIDs. These hypersensitivity reactions differ from the other adverse reactions listed here, which are toxicity reactions, i.e., unwanted reactions that result from the pharmacological action of a drug, are dose-related, and can occur in any treated individual; hypersensitivity reactions are idiosyncratic reactions to a drug. Some NSAID hypersensitivity reactions are truly allergic in origin: 1) repetitive -mediated skin eruptions, , and following immediately to hours after ingesting one structural type of NSAID but not after ingesting structurally unrelated NSAIDs; and 2) Comparatively mild to moderately severe -mediated delayed onset (usually more than 24 hour), skin reactions such as maculopapular rash, fixed drug eruptions, photosensitivity reactions, delayed , and contact dermatitis; or 3) far more severe and potentially life-threatening t-cell-mediated delayed systemic reactions such as the , acute generalized exanthematous pustulosis, the Stevens–Johnson syndrome, and toxic epidermal necrolysis. Other NSAID hypersensitivity reactions are allergy-like symptoms but do not involve true allergic mechanisms; rather, they appear due to the ability of NSAIDs to alter the metabolism of arachidonic acid in favor of forming metabolites that promote allergic symptoms. Affected individuals may be abnormally sensitive to these provocative metabolites or overproduce them and typically are susceptible to a wide range of structurally dissimilar NSAIDs, particularly those that inhibit COX-1. Symptoms, which develop immediately to hours after ingesting any of various NSAIDs that inhibit COX-1, are: 1) exacerbations of asthmatic and rhinitis (see aspirin-exacerbated respiratory disease) symptoms in individuals with a history of or and 2) exacerbation or first-time development of or in individuals with or without a history of chronic lesions or angioedema.

Possible effects on bone and soft tissue healing
It has been hypothesized that NSAIDs may delay healing from and soft-tissue injuries by inhibiting inflammation. On the other hand, it has also been hypothesized that NSAIDs might speed recovery from soft tissue injuries by preventing inflammatory processes from damaging adjacent, non-injured muscles.

There is moderate evidence that they delay bone healing. Their overall effect on soft-tissue healing is unclear.

Ototoxicity
Long-term use of NSAID analgesics and paracetamol is associated with an increased risk of hearing loss.

Other
The use of NSAIDs for analgesia following gastrointestinal surgery remains controversial, given mixed evidence of an increased risk of leakage from any bowel created. This risk may vary according to the class of NSAID prescribed.

Common adverse drug reactions (ADR), other than those listed above, include: raised liver , , . Uncommon ADRs include an , confusion, , and rash. Ibuprofen may also rarely cause irritable bowel syndrome symptoms. NSAIDs are also implicated in some cases of Stevens–Johnson syndrome.

Most NSAIDs penetrate poorly into the central nervous system (CNS). However, the COX enzymes are expressed constitutively in some areas of the CNS, meaning that even limited penetration may cause adverse effects such as somnolence and dizziness.

NSAIDs may increase the risk of bleeding in patients with For this reason, NSAIDs are only available with a prescription in India.

In very rare cases, ibuprofen can cause aseptic meningitis.

(2026). 9780702040863

As with other drugs, to NSAIDs might exist. While many allergies are specific to one NSAID, up to 1 in 5 people may have unpredictable cross-reactive allergic responses to other NSAIDs as well.

Immune response
Although small doses generally have little to no effect on the immune system, large doses of NSAIDs significantly suppress the production of immune cells. As NSAIDs affect prostaglandins, they affect the production of most fast-growing cells. This includes immune cells. Unlike , they do not directly suppress the immune system, and so their effect on the immune system is not immediately obvious. They suppress the production of new immune cells, but leave existing immune cells functional. Large doses slowly reduce the immune response as the immune cells are renewed at a much lower rate. Causing a gradual reduction of the immune system, much slower and less noticeable than the immediate effect of Corticosteroids. The effect significantly increases with dosage, at a nearly exponential rate. Doubling of dose reduced cells by nearly four times. Increasing the dose by five times reduced cell counts to only a few percent of normal levels. This is likely why the effect was not immediately obvious in low-dose trials, as the effect is not apparent until much higher dosages are tested.

Interactions
NSAIDs reduce kidney blood flow and thereby decrease the efficacy of , and inhibit the elimination of lithium and .

NSAIDs cause decreased ability to form blood clots, which can increase the risk of bleeding when combined with other drugs that also decrease blood clotting, such as .

NSAIDs may aggravate (high blood pressure) and thereby antagonize the effect of antihypertensives, such as .

NSAIDs may interfere and reduce effectiveness of antidepressants through inhibiting TNFα and IFNγ, both of which are cytokine derivatives. NSAIDs, when used in combination with SSRIs, increase the risk of adverse gastrointestinal effects. NSAIDs, when used in combination with SSRIs, increase the risk of internal bleeding and brain hemorrhages.

Various widely used NSAIDs enhance signaling by blocking the anandamide-degrading membrane enzyme fatty acid amide hydrolase ().

NSAIDs may reduce the effectiveness of . An study on cultured found that adding NSAIDs to antibiotics reduced their effectiveness by around 20%.

The concomitant use of NSAIDs with alcohol and/or products significantly increases the already elevated risk of during NSAID therapy.

Mechanism of action
Most NSAIDs act as nonselective inhibitors of the (COX) , inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) . This inhibition is competitively reversible (albeit at varying degrees of reversibility), as opposed to the mechanism of , which is irreversible inhibition. COX catalyzes the formation of and from (itself derived from the cellular bilayer by phospholipase A2). Prostaglandins act (among other things) as messenger molecules in the process of . This mechanism of action was elucidated in 1970 by (1927–2004), who received a for his work (see Mechanism of action of aspirin).

COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes. One of these is in the lining, where prostaglandins serve a protective role, preventing the stomach from being eroded by its own acid. COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.

When nonselective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, ulcers of the stomach or and internal can result. The discovery of COX-2 led to research to the development of selective COX-2 inhibiting drugs that do not cause gastric problems characteristic of older NSAIDs.

NSAIDs have been studied in various assays to understand how they affect each of these enzymes. While the assays reveal differences, unfortunately, different assays provide differing ratios.

(acetaminophen) is not considered an NSAID because it has little anti-inflammatory activity. It treats pain mainly by blocking COX-2, mostly in the central nervous system, but not much in the rest of the body.

However, many aspects of the mechanism of action of NSAIDs remain unexplained, and for this reason, further COX pathways are hypothesized. The COX-3 pathway was believed to fill some of this gap, but recent findings make it appear unlikely that it plays any significant role in humans, and alternative explanation models are proposed.

NSAIDs interact with the endocannabinoid system and its , as COX-2 have been shown to utilize endocannabinoids as substrates, and may have a key role in both the therapeutic effects and of NSAIDs, as well as in NSAID-induced responses.

NSAIDs are also used in the acute pain caused by because they inhibit crystal besides inhibition of prostaglandin synthase.

Antipyretic activity
NSAIDs have activity and can be used to treat fever. Fever is caused by elevated levels of prostaglandin E2 (PGE2), which alters the firing rate of neurons within the that control thermoregulation. Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of biosynthesis (PGE2) within the hypothalamus. PGE2 signals to the hypothalamus to increase the body's thermal setpoint. has been shown more effective as an than (acetaminophen). is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D, and E.
(2026). 9781437717389

Classification
NSAIDs can be classified based on their chemical structure or mechanism of action. Older NSAIDs were known long before their mechanism of action was elucidated and were, for this reason, classified by chemical structure or origin. Newer substances are more often classified by mechanism of action.

Salicylates

Propionic acid derivatives

Acetic acid derivatives

Enolic acid (oxicam) derivatives

Anthranilic acid derivatives (Fenamates)
The following NSAIDs are derived from , which is a derivative of ,Sriram D, Yogeeswari P. Medicinal Chemistry, 2nd Edition. Pearson Education India, 2010. which in turn is a nitrogen of , which is the active metabolite of .Auburn University course material. Jack DeRuiter, Principles of Drug Action 2, Fall 2002 1: Non-Steroidal Antiinflammatory Drugs (NSAIDs)

Selective COX-2 inhibitors (Coxibs)

Sulfonanilides
  • (systemic preparations are banned by several countries for the potential risk of hepatotoxicity)

Others

Chirality
Most NSAIDs are chiral molecules; and the are exceptions. However, the majority are prepared as . Typically, only a single is pharmacologically active. For some drugs (typically profens), an in vivo converts the inactive enantiomer into the active form, although its activity varies widely in individuals. This phenomenon is likely responsible for the poor correlation between NSAID efficacy and plasma concentration observed in older studies when specific analysis of the active enantiomer was not performed.
(2013). 9783034804967, Springer Science+Business Media.

and are now available in single-enantiomer preparations (dexibuprofen and dexketoprofen), which purport to offer quicker onset and an improved side-effect profile. has always been marketed as the single active enantiomer.

(2026). 9780511781933, Cambridge University Press. .

Main practical differences
NSAIDs within a group tend to have similar characteristics and tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses. Rather, differences among compounds usually relate to dosing regimens (related to the compound's elimination half-life), route of administration, and tolerability profile.

Regarding adverse effects, selective COX-2 inhibitors have a lower risk of gastrointestinal bleeding. Except for , nonselective NSAIDs increase the risk of having a heart attack. Some data also supports that the partially selective is less likely to cause gastrointestinal events.

A consumer report noted that , naproxen, and are less expensive than other NSAIDs, and essentially as effective and safe when used appropriately to treat osteoarthritis and pain. Treating Osteoarthritis and Pain: The Non-Steroidal Anti-Inflammatory Drugs Comparing Effectiveness, Safety, and Price Consumers Union 2005

Pharmacokinetics
Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3–5. They are absorbed well from the and intestinal mucosa. They are highly protein-bound in plasma (typically >95%), usually to albumin, so that their volume of distribution typically approximates to plasma volume. Most NSAIDs are metabolized in the by and conjugation to inactive metabolites that typically are excreted in the , though some drugs are partially excreted in . Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage.

NSAIDs can also be divided into short-acting (plasma half-life less than 6 h) such as aspirin, diclofenac and ibuprofen and long-acting (half-life approximately greater than 10 h) such as naproxen, celecoxib.

History
It is widely believed that naturally occurring salicin in trees and other plants was used by the ancients as a form of analgesic or anti-inflammatory drug,
(2026). 9781596918160, Chemical Heritage Foundation.
but this story, although compelling, is not entirely true. Hippocrates does not mention willow at all. 's De materia medica was arguably the most influential herbal from Roman to Medieval times but, if he mentions willow at all (there is doubt about the identity of 'Itea'), then he used the ashes, steeped in vinegar, as a treatment for corns, which corresponds well with modern uses of .

Willow bark (from trees of the genus) was widely known to be used as a medicine by multiple First Nations communities.

(2026). 9780816040520, Checkmark Books.
The bark would be chewed or steeped in water for its pain relieving and antipyretic effects. The effects are a result of the bark's salicin content. Meadowsweet, another plant to contain salicin, has strong roots in British folk medicine for the same maladies. Willow bark was first reported in Western science by Edward Stone in 1763 as a treatment for (fever) according to the pseudoscientific doctrine of signatures.

In the body, salicin is turned into salicylic acid, which produces the antipyretic and analgesic effects that the plants are known for.

Salicin was first isolated by Johann Andreas Buchner in 1827. By 1829, French chemist Henri Leroux had improved the extraction process to obtain about 30g of purified salicin from 1.5kg of willow bark.

(1996). 9780070262669, Ed. McGraw-Hill Interamericana.
By , salicin releases and which can be converted into , both and through chemical methods.John McMurry. Química Orgánica (in Spanish). Published by Cengage Learning Editores, 2005. In 1869, synthesised salicylic acid, although it was too acidic for the . The reaction used to synthesise aromatic acid from a in the presence of is known as the Kolbe-Schmitt reaction. (Review)

By 1897, the German chemist and the company prompted a new age of pharmacology by converting salicylic acid into acetylsalicylic acid—named by . Other NSAIDs like were developed from the 1950s forward. In 2001, NSAIDs accounted for 70,000,000 prescriptions and 30billion over-the-counter doses sold annually in the .

Veterinary use
Research supports the use of NSAIDs for the control of pain associated with veterinary procedures such as dehorning and castration of calves. The best effect is obtained by combining a short-term local anesthetic such as with an NSAID acting as a longer term analgesic. However, as different species have varying reactions to different medications in the NSAID family, little of the existing research data can be extrapolated to animal species other than those specifically studied, and the relevant government agency in one area sometimes prohibits uses approved in other jurisdictions.

In the United States, is approved for use only in canines, whereas (due to concerns about kidney damage) it carries warnings against its use in catsMetacam Client Information Sheet , product description: "Non-steroidal anti-inflammatory drug for oral use in dogs only", and in the "What Is Metacam" section in bold-face type: "Do not use in cats.", January 2005. except for one-time use during surgery. Metacam 5 mg/mL Solution for Injection, Supplemental Approval 28 October 2004. In spite of these warnings, meloxicam is frequently prescribed "off-label" for non-canine animals including cats and livestock species.Off-label use discussed in: Arnold Plotnick MS, DVM, ACVIM, ABVP, Pain Management using Metacam , and Stein, Robert, Perioperative Pain Management Part IV, Looking Beyond Butorphanol, September 2006. In other countries, for example (EU), there is a label claim for use in cats.

See also
  • Discovery and development of cyclooxygenase 2 inhibitors

External links
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