Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs—but also referred to as nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal anti-inflammatory medicines (NSAIMs)—are a class of anti-inflammatory effects.
The term “nonsteroidal” distinguishes these drugs from narcotic.
 Medical uses
NSAIDs are usually indicated for the treatment of acute or chronic conditions where cardiovascular disease.
NSAIDs are generally indicated for the symptomatic relief of the following conditions:
- Rheumatoid arthritis
- Inflammatory arthropathies (e.g. Reiter’s syndrome)
- Acute gout
- menstrual pain)
- Metastatic bone pain
- Postoperative pain
- Mild-to-moderate pain due to inflammation and tissue injury
- Muscle stiffness and pain due to Parkinson’s disease
- Renal colic
- They are also given to neonate infants whose ductus arteriosus is not closed within 24 hours of birth
 Adverse effects
The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly prevalent. The two main renal effects of NSAIDs.
These 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 dyspepsia, 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.
NSAIDs, like all drugs, may interact with other medications. For example, concurrent use of NSAIDs and 
 Combinational risk
If a COX-2 inhibitor is taken, one should not use a traditional NSAID (prescription or over-the-counter) concomitantly. In addition, people on daily aspirin therapy (e.g., for reducing cardiovascular risk) must be careful if they also use other NSAIDs, as the latter may block[further explanation needed] the cardioprotective effects of aspirin.
NSAIDs aside from aspirin, both newer selective COX-2 inhibitors and traditional anti-inflammatories, increase the risk of 
NSAIDs aside from (low-dose) aspirin are associated with a doubled risk of symptomatic heart failure in patients without a history of cardiac disease. In patients with such a history, however, use of NSAIDs (aside from low-dose aspirin) was associated with a more than 10-fold increase in heart failure.
 Erectile dysfunction risk
A 2005 study linked long term (over 3 months) use of NSAIDs, including ibuprofen, with a 1.4 times increased risk of 
The main adverse drug reactions (clarification needed] effects on epithelial mucosa.
Common gastrointestinal ADRs 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 patients with achlorhydria.
Ulceration risk increases with therapy duration, and with higher doses. To minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time—a practice that studies show is often not followed. Recent studies show that over 50% of patients that take NSAIDs have sustained some mucosal damage to their small intestine.
There are also some differences in the propensity of individual agents to cause gastrointestinal ADRs. Indomethacin, ketoprofen and piroxicam appear to have the highest prevalence of gastric ADRs, while ibuprofen (lower doses) and diclofenac appear to have lower rates.
Certain NSAIDs, such as aspirin, have been marketed in enteric-coated formulations that manufacturers claim reduce the incidence of gastrointestinal ADRs. Similarly, some believe that rectal formulations may reduce gastrointestinal ADRs. However, considering the mechanism of such ADRs, and in clinical practice, these formulations have not demonstrated a reduced risk of GI ulceration.
Commonly, gastric (but not necessarily intestinal) adverse effects can be reduced through suppressing acid production, by concomitant use of a misoprostol. Misoprostol is itself associated with a high incidence of gastrointestinal ADRs (diarrhea). While these techniques may be effective, they are expensive for maintenance therapy.
 Inflammatory bowel disease
NSAIDs should be used with caution in individuals with citation needed]
NSAIDs are also associated with a relatively high incidence of renal adverse drug reactions (renal function. This is particularly important in renal 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. Prostaglandins serve to dilate the afferent arteriole; by blocking this prostaglandin-mediated effect, particularly in renal failure, NSAIDs cause unopposed constriction of the afferent arteriole and decreased renal perfusion pressure.
Common ADRs associated with altered renal function include:
- Salt and fluid retention
- Hypertension (high blood pressure)
These agents may also cause renal impairment, especially in combination with other nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor (which removes angiotensin II’s vasoconstriction of the efferent arteriole) and a diuretic (which drops plasma volume, and thereby RPF) – the so-called “triple whammy” effect.
In rarer instances NSAIDs may also cause more severe renal conditions:
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 piroxicam, diclofenac and benzydamine.
Benoxaprofen, since withdrawn due to its hepatotoxicity, was the most photoactive NSAID observed. The mechanism of photosensitivity, responsible for the high photoactivity of the 2-arylpropionic acids, is the ready decarboxylation of the carboxylic acid moiety. The specific absorbance characteristics of the different chromophoric 2-aryl substituents, affects the decarboxylation mechanism. While ibuprofen has weak absorption, it has been reported as a weak photosensitising agent.
 During pregnancy
NSAIDs are not recommended during pregnancy, particularly during the third trimester. While NSAIDs as a class are not direct teratogens, they may cause premature closure of the fetal ductus arteriosus and renal ADRs in the fetus. Additionally, they are linked with premature birth and miscarriage. Aspirin, however, is used together with heparin in pregnant women with antiphospholipid antibodies. Additionally, Indomethacin is used in pregnancy to treat polyhydramnios by reducing fetal urine production via inhibiting fetal renal blood flow.
In contrast, 
In France, the country’s health agency contraindicates the use of NSAIDs, including aspirin, after the sixth month of pregnancy.
Common adverse drug reactions (ADR), other than listed above, include: raised liver 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.
In very rare cases, ibuprofen can cause aseptic meningitis.
As with other drugs, allergies 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.
 Drug interactions
NSAIDs may aggravate 
NSAIDs may interfere and reduce efficiency of 
 Mechanism of action
COX-1 is a constitutively expressed enzyme with a “house-keeping” role in regulating many normal physiological processes. One of these is in the Brigham Young University. 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, bleeding can result.
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.,
The discovery of COX-2 led to research to development of selective COX-2 inhibiting drugs that do not cause gastric problems characteristic of older NSAIDs.
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, 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.
 Antipyretic activity
Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D & E.
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.
 Propionic acid derivatives
 Acetic acid derivatives
- Diclofenac (Safety alert by FDA)
- Nabumetone (drug itself is non-acidic but the active, principal metabolite has a carboxylic acid group)
 Enolic acid (Oxicam) derivatives
 Fenamic acid derivatives (Fenamates )
 Selective COX-2 inhibitors (Coxibs)
- Celecoxib (FDA alert)
- Rofecoxib (withdrawn from market)
- Valdecoxib (withdrawn from market)
- Parecoxib FDA withdrawn, licenced in the EU
- Lumiracoxib TGA cancelled registration
- Etoricoxib not FDA approved, licenced in the EU
- Firocoxib used in dogs and horses
- Nimesulide (systemic preparations are banned by several countries for the potential risk of hepatotoxicity)
- Licofelone acts by inhibiting LOX (lipooxygenase) & COX and hence known as 5-LOX/COX inhibitor
A related drug, Paracetamol or “acetaminophen” is often considered in the same category as NSAIDS due to its use as a non-narcotic analgesic and fever-reducing agent, but is not classified as a NSAID because it only exerts weak anti-inflammatory effects.
 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 lower risk of gastrointestinal bleeding, but a substantially more increased risk of 
A consumer report noted that ibuprofen, naproxen, and salsalate are less expensive than other NSAIDs, and essentially as effective and safe when used appropriately to treat osteoarthritis and pain.
Most nonsteroidal anti-inflammatory drugs are weak acids, with a pKa of 3-5. They are absorbed well from the bile. Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage.
Ibuprofen and diclofenac have short half-lives (2–3 hours). Some NSAIDs (typically oxicams) have very long half-lives (e.g. 20–60 hours).
Most NSAIDs are enzyme 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.
Ibuprofen and ketoprofen are now available in single, active enantiomer preparations (dexibuprofen and dexketoprofen), which purport to offer quicker onset and an improved side-effect profile. Naproxen has always been marketed as the single active enantiomer.
 Controversies with COX-2 inhibitors
—which caused a worldwide withdrawal of rofecoxib in October 2004.
 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 lidocaine 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.
For example, flunixin meglumine, which, while labeled for use in such animals, is not indicated for post-operative pain.
In the United States, citation needed]
- Some Common Medications That Contain Acetaminophen
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- Metacam 5 mg/mL Solution for Injection, Supplemental Approval 28 October 2004.
- Off-label use discussed in: Arnold Plotnick MS, DVM, ACVIM, ABVP, Pain Management using Metacam, and Stein, Robert, Perioperative Pain Managemment Part IV, Looking Beyond Butorphanol, September 2006.
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