Non-steroidal anti-inflammatory drug: Wikis

  
  

Encyclopedia

From Wikipedia, the free encyclopedia

.Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, are drugs with analgesic, antipyretic (lowering an elevated body temperature and relieving pain without impairing consciousness) and, in higher doses, with anti-inflammatory effects (reducing inflammation).^ (Brand Name of Drug) is a non-steroidal anti-inflammatory drug ( NSAID ).
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ NSAIDs and Aspirin - NSAIDs are common medications used to reduce pain and inflammation.
  • Acetaminophen and NSAID Toxicity - Be Safe with Natural Cox 2 Inhibitors 1 February 2010 3:33 UTC www.qfac.com [Source type: Academic]

^ Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders.
  • Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts -- Zavarella et al. 85 (5): 452 -- Journal of Dental Research 11 January 2010 2:18 UTC jdr.sagepub.com [Source type: Academic]

.The term "non-steroidal" is used to distinguish these drugs from steroids, which (among a broad range of other effects) have a similar eicosanoid-depressing, anti-inflammatory action.^ (Brand Name of Drug) is a non-steroidal anti-inflammatory drug ( NSAID ).
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders.
  • Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts -- Zavarella et al. 85 (5): 452 -- Journal of Dental Research 11 January 2010 2:18 UTC jdr.sagepub.com [Source type: Academic]

^ DERAMAXX (deracoxib) is a non-narcotic, non-steroidal anti-inflammatory drug of the coxib class.
  • VetRxDirect - Deramaxx (deracoxib): Chewable NSAID Tablets for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

.As analgesics, NSAIDs are unusual in that they are non-narcotic.^ As analgesics, NSAIDs are unusual in that they are non- narcotic .
  • Non-steroidal anti-inflammatory drug - Psychology Wiki 1 February 2010 3:33 UTC psychology.wikia.com [Source type: Academic]

^ NSAIDs are sometimes also referred to as non-steroidal anti-inflammatory agents/analgesics ( NSAIAs ) or non-steroidal anti-inflammatory medicines ( NSAIMs ).
  • Non-steroidal anti-inflammatory drug - Psychology Wiki 1 February 2010 3:33 UTC psychology.wikia.com [Source type: Academic]

^ Analgesics that do not contain NSAIDs, such as acetaminophen, might not provide sufficient pain relief, 7,8 and the use of narcotic analgesics can be associated with substantial cognitive side effects.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]

.NSAIDs are sometimes also referred to as non-steroidal anti-inflammatory agents/analgesics (NSAIAs) or non-steroidal anti-inflammatory medicines (NSAIMs).^ (Brand Name of Drug) is a non-steroidal anti-inflammatory drug ( NSAID ).
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders.
  • Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts -- Zavarella et al. 85 (5): 452 -- Journal of Dental Research 11 January 2010 2:18 UTC jdr.sagepub.com [Source type: Academic]

^ Are non-steroidal anti-inflammatory drugs always necessary?
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

.The most prominent members of this group of drugs are aspirin, ibuprofen, and naproxen partly because they are available over-the-counter in many areas.^ Meloxicam is a member of the class of drugs known as NSAIDs (non-steroidal anti-inflammatory drugs), the same class as such common over-the-counter remedies as Advil (Ibuprofen), Aleve (Naproxen), Orudis (ketoprofen), and aspirin as well as more controversial prescription drug such as Celebrex (celecoxib) and Vioxx (rofecoxib).
  • Rimadyl, Deramaxx, Previcox, Zubrin, Meloxicam and other NSAID's 1 February 2010 3:33 UTC www.k911.biz [Source type: FILTERED WITH BAYES]

^ Ibuprofen and diclofenac were classified as low risk; aspirin, sulindac, naproxen and indomethacin as moderate risk; and ketoprofen and piroxicam as high risk for GI side effects.
  • BioMed Central | Full text | Non-steroidal anti-inflammatory drugs cyclooxygenase-2 inhibitors and paracetamol use in Queensland and in the whole of Australia 11 January 2010 2:18 UTC www.biomedcentral.com [Source type: Academic]

^ Our study is limited by the lack of data on over-the- counter use of aspirin, naproxen, or ibuprofen and by there being no prescription records for low dosages available over the counter.
  • Arch Intern Med -- Selective Cyclooxygenase-2 Inhibition and Cardiovascular Effects: An Observational Study of a Medicaid Population, January 24, 2005, Shaya et al. 165 (2): 181 1 February 2010 3:33 UTC archinte.ama-assn.org [Source type: Academic]

Contents

Mechanism of action

.Most NSAIDs act as non-selective inhibitors of the enzyme cyclooxygenase, inhibiting both the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes.^ NSAIDs as a class comprise both traditional nonselective NSAIDs (tNSAIDs) that nonspecifically inhibit both COX-1 and COX-2, and selective COX-2 inhibitors.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ COX-2 is also inhibited by selective NSAIDs.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

^ With the development of “COX preferential” and “COX selective” NSAIDs, we can inhibit COX-2 and leave COX-1 alone.
  • Rimadyl, Deramaxx, Previcox, Zubrin, Meloxicam and other NSAID's 1 February 2010 3:33 UTC www.k911.biz [Source type: FILTERED WITH BAYES]

.Cyclooxygenase catalyzes the formation of prostaglandins and thromboxane from arachidonic acid (itself derived from the cellular phospholipid bilayer by phospholipase A2).^ Aspirin and other NSAIDs inhibit the expression of the cyclooxygenase 2 (COX-2) gene, which encodes one of two cyclooxygenase enzymes that catalyzes the synthesis of prostaglandins from the dietary fatty acid arachidonic acid.
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

^ Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) inhibited both isoforms of the enzyme cyclooxygenase responsible for the first step in the conversion of arachidonic acid into a variety of prostaglandins, thromboxanes, and leukotrienes throughout the body.
  • JAMA -- COX-2 Inhibitors, Other NSAIDs, and Cardiovascular Risk: The Seduction of Common Sense, September 12, 2006, Graham 0 (2006): 296.13.jed60058 1 February 2010 3:33 UTC jama.ama-assn.org [Source type: Academic]

^ NSAIDs work by inhibiting cyclooxygenase (COX-1 and COX-2) enzymes, which convert arachidonic acid to pro-inflammatory prostaglandins (Schoenfeld P et al 1999).
  • Acetaminophen and NSAID Toxicity: Online References For Health Concerns 1 February 2010 3:33 UTC www.lef.org [Source type: Academic]
  • Acetaminophen and NSAID Toxicity - Be Safe with Natural Cox 2 Inhibitors 1 February 2010 3:33 UTC www.qfac.com [Source type: Academic]

.Prostaglandins act (among other things) as messenger molecules in the process of inflammation.^ However, it seems likely that a range of biologically active lipid molecules are involved in the regulation of biofilm formation, morphogenesis, and other major physiological processes in C. albicans .
  • Effects of Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs on Biofilms and Planktonic Cells of Candida albicans -- Alem and Douglas 48 (1): 41 -- Antimicrobial Agents and Chemotherapy 11 January 2010 2:18 UTC aac.asm.org [Source type: Academic]

^ In addition, because other substances in addition to prostaglandins are involved in inflammation, and nonsteroidal antiinflammatory agents do not act exclusively by inhibition of prostaglandin synthesis, the therapeutic benefit of antiinflammatory agents in gastrointestinal mucosa may be due to several mechanisms.

.This mechanism of action was elucidated by John Vane (1927-2004), who later received a Nobel Prize for his work (see Mechanism of action of aspirin).^ Commercially available nonprescription NSAIDs The inhibition of prostaglandin production by NSAIDs was first demonstrated in 1971; this work ultimately led to the researchers receiving a Nobel Prize in Medicine [ 3 ].
  • Osteopathic Medicine and Primary Care | Full text | A review of the benefits and risks of nonsteroidal anti-inflammatory drugs in the management of mild-to-moderate osteoarthritis 11 January 2010 2:18 UTC www.om-pc.com [Source type: Academic]

^ Medline ↵ Tarnawski AS, Caves TC. Aspirin in the XXI century: its major clinical impact, novel mechanisms of action, and new safer formulations.
  • Nonsteroidal Anti-inflammatory Drugs and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County — Cancer Epidemiology, Biomarkers & Prevention 1 February 2010 3:33 UTC cebp.aacrjournals.org [Source type: Academic]

^ Vane J, Botting R. Inflammation and the mechanism of action of anti-inflammatory drugs.
  • Comparative Effects of the Nonsteroidal Anti-inflammatory Drug Nepafenac on Corneal Sensory Nerve Fibers Responding to Chemical Irritation -- Acosta et al. 48 (1): 182 -- Investigative Ophthalmology & Visual Science 11 January 2010 2:18 UTC www.iovs.org [Source type: Academic]

.A newly discovered COX-3 may also have some role.^ It has been suggested by some authors that COX-2 inhibitors may safely be used by patients with tNSAIDs intolerance.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ Some studies suggested that celecoxib and lumiracoxib may have a slightly better safety profile than other COX-2 inhibitors.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ These compounds can be used to dissect the role of the AKR1C isozymes in neoplastic diseases and may have cancer chemopreventive roles independent of COX inhibition.
  • Development of Nonsteroidal Anti-Inflammatory Drug Analogs and Steroid Carboxylates Selective for Human Aldo-Keto Reductase Isoforms: Potential Antineoplastic Agents That Work Independently of Cyclooxygenase Isozymes — Molecular Pharmacology 11 January 2010 2:18 UTC molpharm.aspetjournals.org [Source type: Academic]

Classes

.NSAIDs can be broadly classified based on their chemical structure.^ The compound is weakly acidic (pKa=6.5) and differs from other NSAIDs in that its chemical structure contains a sulfonanilide moeity as the acidic group.
  • Pharmaceutical compositions containing at least one NSAID having increased bioavailability - Patent 6017932 1 February 2010 3:33 UTC www.freepatentsonline.com [Source type: Academic]

^ A variety of NSAIDs can block the enzymatic activity of COX; they vary in their chemical structure and relative ability to block the COX-1 versus the COX-2 isoenzymes ( Figure 4 ).
  • Use of Nonsteroidal Antiinflammatory Drugs: An Update for Clinicians: A Scientific Statement From the American Heart Association -- Antman et al. 115 (12): 1634 -- Circulation 11 January 2010 2:18 UTC circ.ahajournals.org [Source type: Academic]

Propionic acid derivatives

Acetic acid derivatives

  1. REDIRECT [[I6]]

Enolic acid (Oxicam) derivatives

Fenamic acid derivatives

Selective COX-2 inhibitors (Coxibs)

Examples

.NSAIDs within a group will tend to have similar characteristics and tolerability.^ Table 1 - Characteristics of NSAID and non-NSAID groups.
  • Journal of Human Hypertension - NSAID use and BP in treated hypertensives: a retrospective controlled observational study 1 February 2010 3:33 UTC www.nature.com [Source type: Academic]

^ When stratifying by MSI status, the joint association between smoking and NSAID use in colorectal cancer risk for MSI-L/MSS tumors was similar to that of the combined group.
  • Risk of Microsatellite-Unstable Colorectal Cancer Is Associated Jointly with Smoking and Nonsteroidal Anti-inflammatory Drug Use -- Chia et al. 66 (13): 6877 -- Cancer Research 1 February 2010 3:33 UTC cancerres.aacrjournals.org [Source type: Academic]

^ RESULTS Patient Characteristics Table 1A and Table 1B present the baseline characteristics of PPI-compliant and PPI-noncompliant groups for the COX-2–selective and nonselective NSAID populations.
  • Impact of Compliance With Proton Pump Inhibitors on NSAID Treatment 1 February 2010 3:33 UTC www.ajmc.com [Source type: Academic]

.There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses.^ Use of the maximum recommended doses of NSAIDs.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice 11 January 2010 2:18 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • BioMed Central | Full text | Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]

^ Use the lowest NSAID dose possible.
  • Back Pain and Sciatica 1 February 2010 3:33 UTC adam.about.com [Source type: Academic]

^ Nimesulide therapy was characterised by a rapid onset of analgesia and symptomatic relief in studies where a significant difference in clinical efficacy between active treatments was observed.
  • Pharmaceutical compositions containing at least one NSAID having increased bioavailability - Patent 6017932 1 February 2010 3:33 UTC www.freepatentsonline.com [Source type: Academic]

.Rather, differences among compounds tend to be with regards to dosing regimens (related to the compound's elimination half-life), route of administration, and tolerability profile.^ Half-life elimination: Normal renal function: 12-17 hours; End-stage renal disease: No change .
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Meloxicam 15 mg once daily for 7 days did not alter the plasma concentration profile of digoxin after β-acetyldigoxin administration for 7 days at clinical doses.
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ The elimination half-life of 4-hydroxy-nimesulide ranges from 2.89 to 4.75 hours and is generally similar to or slightly higher than that of the parent compound (1.56 to 4.95 h).
  • Pharmaceutical compositions containing at least one NSAID having increased bioavailability - Patent 6017932 1 February 2010 3:33 UTC www.freepatentsonline.com [Source type: Academic]

.Some more common examples are given below.^ Some more common examples are given below.
  • Chemistry - Non-steroidal anti-inflammatory drug 11 January 2010 2:18 UTC www.chemistrydaily.com [Source type: Academic]
  • NSAID's -- Non-steroidal anti-inflammatory drugs 11 January 2010 2:18 UTC www.worldofmolecules.com [Source type: Academic]

^ The following examples are given to enable those skilled in the art to more clearly understand and to practice the present invention.
  • Ophthalmic NSAID formulations containing a quaternary ammonium preservative and a nonionic surfactant - Patent 5110493 1 February 2010 3:33 UTC www.freepatentsonline.com [Source type: Reference]

^ While they can be very useful in controlling pain and inflammation, like corticosteroids they too have side effects, some more serious and dangerous than others (see below.
  • Non-Steroidal Anti-Inflammatory Medications (NSAIDS) for Pets 11 January 2010 2:18 UTC www.glucosamine-arthritis.org [Source type: FILTERED WITH BAYES]

Sulphonanilides

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

Others

.Licofelone acts by inhibiting LOX (lipooxygenase) & COX (cyclooxygenase)and hence known as 5-LOX/COX inhibitor.^ Cyclooxygenase has 2 known isoforms, COX-1 and COX-2.
  • Arch Otolaryngol Head Neck Surg -- Postoperative Hemorrhage With Nonsteroidal Anti-inflammatory Drug Use After Tonsillectomy: A Meta-analysis, October 2003, Krishna et al. 129 (10): 1086 11 January 2010 2:18 UTC archotol.ama-assn.org [Source type: Academic]

^ Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade.
  • NEJM -- Gastrointestinal Toxicity of Nonsteroidal Antiinflammatory Drugs 11 January 2010 2:18 UTC content.nejm.org [Source type: Academic]

^ Cyclooxygenase-2 inhibitors are a subclass of NSAIDs which specifically inhibit the production of compounds that mediate pain and inflammation via COX-2, while not affecting the production of gastroprotective prostaglandins through the action of cyclooxygenase-1.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]

Uses

.NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present.^ There is still a controversy as to which NSAID is better in chronic pain conditions.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ Thus, coxibs are as effective as other NSAIDs in the treatment of pain and inflammation.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

^ Cyclooxygenase-2 inhibitors are a subclass of NSAIDs which specifically inhibit the production of compounds that mediate pain and inflammation via COX-2, while not affecting the production of gastroprotective prostaglandins through the action of cyclooxygenase-1.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]

.Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions, such as cancer and cardiovascular disease.^ Because inhibition of cyclooxygenase-2 enzyme has been considered to be helpful in other conditions, coxibs have also been used in patients with Alzheimer's disease (extrapolated 10-year risk of an APTC event about 22% [ 18 ]), and following colorectal cancer surgery to prevent recurrence (extrapolated 10-year risk of an APTC event about 5% [ 18 ]).
  • BioMed Central | Full text | Cyxlo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]

^ Some researchers have used this data to advocate chili or capsaicin as treatment for peptic ulcer disease, 21 but check with your doctor before trying to self-treat this serious condition.
  • Nonsteroidal Anti-inflammatory Drugs 11 January 2010 2:18 UTC healthlibrary.epnet.com [Source type: Academic]
  • Nonsteroidal Anti-inflammatory Drugs - Content Viewer 11 January 2010 2:18 UTC www.svmh.com [Source type: Academic]
  • Nonsteroidal Anti-inflammatory Drugs | ThirdAge Articles 11 January 2010 2:18 UTC www.thirdage.com [Source type: Academic]
  • Nonsteroidal Anti-inflammatory Drugs | Lifescript.com 11 January 2010 2:18 UTC www.lifescript.com [Source type: Academic]

^ Cardiovascular and cerebrovascular events in the randomized, controlled Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT).
  • Use of Nonsteroidal Antiinflammatory Drugs: An Update for Clinicians: A Scientific Statement From the American Heart Association -- Antman et al. 115 (12): 1634 -- Circulation 11 January 2010 2:18 UTC circ.ahajournals.org [Source type: Academic]

NSAIDs are generally indicated for the symptomatic relief of the following conditions:[6]
.
  • Rheumatoid arthritis[7]
  • Osteoarthritis
  • Inflammatory arthropathies (e.g.^ For extended-release tablet dosage form: For rheumatoid arthritis, osteoarthritis, or spondylitis: AdultsUsually 400 to 1000 mg once a day.
    • Drug Profiles: Nonsteroidal Anti-Inflammatory Drugs: NSAIDs 11 January 2010 2:18 UTC www.migraines.org [Source type: General]

    ^ For rheumatoid arthritis or osteoarthritis: AdultsAt first, 250 or 500 mg twice a day.
    • Drug Profiles: Nonsteroidal Anti-Inflammatory Drugs: NSAIDs 11 January 2010 2:18 UTC www.migraines.org [Source type: General]

    ^ Celecoxib was listed as a restricted benefit for symptomatic treatment of osteoarthritis (OA) and rheumatoid arthritis (RA).
    • BioMed Central | Full text | Non-steroidal anti-inflammatory drugs cyclooxygenase-2 inhibitors and paracetamol use in Queensland and in the whole of Australia 11 January 2010 2:18 UTC www.biomedcentral.com [Source type: Academic]

    ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome)
  • Acute gout
  • Dysmenorrhoea (menstrual pain)
  • Metastatic bone pain
  • Headache and migraine
  • Postoperative pain
  • Mild-to-moderate pain due to inflammation and tissue injury
  • Pyrexia (fever)
  • Ileus
  • Renal colic
  • They are also given to neonate infants whose ductus arteriosus is not closed within 24 hours of birth
.Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation.^ COX-2 is also inhibited by selective NSAIDs.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

^ Aspirin is a potent inhibitor of platelet COX-1 and induces irreversible inhibition of platelet aggregation.
  • Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs: A Nested Case-Control Study * Editorial Comment -- Bak et al. 34 (2): 379 -- Stroke 11 January 2010 2:18 UTC stroke.ahajournals.org [Source type: Academic]

^ Aspirin differs from other NSAIDs because it irreversibly inhibits platelet aggregation, and the salicylic acid derivatives (aspirin and salsalate) were considered a separate subgroup.
  • Search for Guides, Reviews, and Reports - AHRQ Effective Health Care Program 1 February 2010 3:33 UTC effectivehealthcare.ahrq.gov [Source type: Academic]

.This is useful in the management of arterial thrombosis and prevention of adverse cardiovascular events.^ Use of (Brand Name of Drug) should be limited to the lowest effective dose for the shortest possible duration of treatment in order to minimize the potential risk for cardiovascular or gastrointestinal adverse events.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Use of some is associated with an increased incidence of cardiovascular adverse events (such as myocardial infarction, stroke or thrombotic events) which can be fatal.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

Aspirin inhibits platelet aggregation by inhibiting the action of thromboxane -A.
.In 2001 NSAIDs accounted for 70,000,000 prescriptions and 30 billion over-the-counter doses sold annually in the United States.^ More than 70 million NSAID prescriptions are written each year, and 30 billion over-the-counter NSAID tablets are sold annually.
  • Ditch your NSAID meds | The Blog of Michael R. Eades, M.D. 1 February 2010 3:33 UTC www.proteinpower.com [Source type: General]
  • Michael R. Eades, M.D.: Ditch your NSAID meds 1 February 2010 3:33 UTC www.proteinpower.com [Source type: General]

^ All told, more than 30 billion doses of NSAIDs are consumed annually in the United States alone.
  • Acetaminophen and NSAID Toxicity: Online References For Health Concerns 1 February 2010 3:33 UTC www.lef.org [Source type: Academic]
  • Acetaminophen and NSAID Toxicity - Be Safe with Natural Cox 2 Inhibitors 1 February 2010 3:33 UTC www.qfac.com [Source type: Academic]

^ Every year, in the U.S., over 70 million prescriptions are written for NSAIDs, and over 30 billion tablets are sold over-the-counter.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

[8]
.One study has suggested that taking NSAIDs while smoking marijuana may prevent the death of brain cells resulting from THC intoxication.^ These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process.
  • Risk of Alzheimer's disease and duration of NSAID use -- Stewart et al. 48 (3): 626 -- Neurology 1 February 2010 3:33 UTC www.neurology.org [Source type: Academic]

^ NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year.
  • Back Pain and Sciatica 1 February 2010 3:33 UTC adam.about.com [Source type: Academic]

^ Some studies have reported a higher incidence of heart attacks in patients taking Vioxx compared to those taking standard NSAIDs.
  • Back Pain and Sciatica 1 February 2010 3:33 UTC adam.about.com [Source type: Academic]

[9] However, neurotoxicity of marijuana is still a matter of dispute.

Pharmacokinetics

.Most non-steroidal anti-inflammatory drugs are weak acids, with a pKa of 3-5. They are absorbed well from the stomach and intestinal mucosa.^ Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders.
  • Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts -- Zavarella et al. 85 (5): 452 -- Journal of Dental Research 11 January 2010 2:18 UTC jdr.sagepub.com [Source type: Academic]

^ What to watch for in dogs on non-steroidal anti-inflammatory drugs (NSAIDs): .
  • Rimadyl, Deramaxx, Previcox, Zubrin, Meloxicam and other NSAID's 1 February 2010 3:33 UTC www.k911.biz [Source type: FILTERED WITH BAYES]

^ Are non-steroidal anti-inflammatory drugs always necessary?
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

.They are highly protein-bound in plasma (typically >95%), usually to albumin, so that their volume of distribution typically approximates to plasma volume.^ Flurbiprofen plasma protein binding may be decreased in patients with liver disease and serum albumin concentrations below 3.1 g/dL (see PRECAUTIONS, Hepatic Effects ).
  • Flurbiprofen Official FDA information, side effects and uses. 18 September 2009 7:52 UTC www.drugs.com [Source type: Academic]

^ Both Flurbiprofen enantiomers are more than 99% bound to plasma proteins, primarily albumin.
  • Flurbiprofen Official FDA information, side effects and uses. 18 September 2009 7:52 UTC www.drugs.com [Source type: Academic]

^ The drug is 97% bound to canine plasma proteins.
  • VetRxDirect - Metacam Oral Suspension NSAID Pain Reliever for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

.Most NSAIDs are metabolised in the liver by oxidation and conjugation to inactive metabolites which are typically excreted in the urine, although some drugs are partially excreted in bile.^ Deracoxib is not excreted as parent drug in the urine.
  • VetRxDirect - Deramaxx (deracoxib): Chewable NSAID Tablets for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

^ The majority of deracoxib is excreted in feces as parent drug or metabolite.
  • VetRxDirect - Deramaxx (deracoxib): Chewable NSAID Tablets for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

^ Most patients made active decisions about using or not using NSAIDs, with some favouring physical function over safety.
  • eMJA: Non-steroidal anti-inflammatory drugs in general practice: a decision-making dilemma 11 January 2010 2:18 UTC www.mja.com.au [Source type: Academic]

.Metabolism may be abnormal in certain disease states, and accumulation may occur even with normal dosage.^ Hepatic insufficiency: Hepatic metabolism may account for > 90% of Flurbiprofen elimination, so patients with hepatic disease may require reduced doses of Flurbiprofen tablets, USP compared to patients with normal hepatic function.
  • Flurbiprofen Official FDA information, side effects and uses. 18 September 2009 7:52 UTC www.drugs.com [Source type: Academic]

^ Even with therapeutic INR monitoring, increased bleeding may occur.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Your doctor may want to do certain tests to find out if unwanted effects are occurring, especially if you are taking phenylbutazone.
  • Anti-inflammatory Drugs, Nonsteroidal (Systemic) 11 January 2010 2:18 UTC allnutritionals.com [Source type: General]

.Ibuprofen and diclofenac have short half-lives (2–3 hours).^ Siegmeth W, Sieberer W. A comparison of the short-term effects of ibuprofen and diclofenac in spondylosis.
  • Nonsteroidal Anti-Inflammatory Drugs for Low Back Pain: Abstract and Introduction 11 January 2010 2:18 UTC www.medscape.com [Source type: Academic]

^ The immediate-release form provides short-lived relief, usually for less than 3 hours.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

.Some NSAIDs (typically oxicams) have very long half-lives (e.g.^ For management of chronic/persistent pain, administration of NSAIDs with long half-lives has clear advantages in allowing for once- or twice-a-day dosing (e.g., naproxen, COX-2 inhibitors).
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ Other NSAIDs should be withheld preop-eratively for five elimination half-lives of the medication.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

^ In fact, an increased risk was apparent only for breast cancers diagnosed some years after long-term NSAID use was already achieved.
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

20–60 hours).

Adverse effects

.The widespread use of NSAIDs has meant that the adverse effects of these drugs have become increasingly prevalent.^ General NSAIDs and adverse effects .

^ Current use and never use of each of these drugs were defined as for NSAIDs.
  • Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs: A Nested Case-Control Study * Editorial Comment -- Bak et al. 34 (2): 379 -- Stroke 11 January 2010 2:18 UTC stroke.ahajournals.org [Source type: Academic]

^ The burden of NSAID adverse effects in the UK .

.The two main adverse drug reactions (ADRs) associated with NSAIDs relate to gastrointestinal (GI) effects and renal effects of the agents.^ Concerns related to adverse effects: .
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Laine L: Gastrointestinal effects of NSAIDs and coxibs.
  • BioMed Central | Full text | Non-steroidal anti-inflammatory drugs cyclooxygenase-2 inhibitors and paracetamol use in Queensland and in the whole of Australia 11 January 2010 2:18 UTC www.biomedcentral.com [Source type: Academic]

^ How big is the problem of NSAID GI adverse effects?

.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.^ Previous history of gastroduodenal ulcer, gastrointestinal bleeding, or gastroduodenal perforation.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice 11 January 2010 2:18 UTC www.ncbi.nlm.nih.gov [Source type: Academic]
  • BioMed Central | Full text | Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]

^ Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin Am J Gastroenterol.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]

.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.^ The cost associated with NSAID adverse effects has been estimated at $1.86 billion.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

^ In the United States alone, NSAID use has been extrapolated to account for approximately 107000 hospitalizations and 16 500 deaths per year among patients with arthritis.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ In over 10% of patients the nephropathy was judged to be related to the use of these drugs.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

.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.^ Results: Unnecessary prescriptions for NSAIDs or other drugs were written during 41.7% of visits.
  • Unnecessary Prescribing of NSAIDs and the Management of NSAID-Related Gastropathy in Medical Practice — Ann Intern Med 1 February 2010 3:33 UTC www.annals.org [Source type: Academic]

^ Unnecessary NSAID prescriptions were written in 52 (37.4%) visits.
  • Unnecessary Prescribing of NSAIDs and the Management of NSAID-Related Gastropathy in Medical Practice — Ann Intern Med 1 February 2010 3:33 UTC www.annals.org [Source type: Academic]

^ Furthermore, there are many methodological shortcomings to the small individual studies included in these systematic reviews.
  • Journal of Human Hypertension - NSAID use and BP in treated hypertensives: a retrospective controlled observational study 1 February 2010 3:33 UTC www.nature.com [Source type: Academic]

[8]
.NSAIDs, like all drugs, may interact with other medications.^ Assess effectiveness and interactions of other medications patient may be taking.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Assess other medications patient may be taking for effectiveness and interactions.
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ In relation to drug–drug interactions, NSAIDs may antagonise angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-II receptor antagonists, diuretics and beta-blockers.
  • Journal of Human Hypertension - NSAID use and BP in treated hypertensives: a retrospective controlled observational study 1 February 2010 3:33 UTC www.nature.com [Source type: Academic]

.For example, concurrent use of NSAIDs and quinolones may increase the risk of quinolones' adverse central nervous system effects, including seizure.^ The use of a NSAID close to conception may be associated with an increased risk of miscarriage.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Central nervous system: Dizziness, hypaesthesia .
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Risk of adverse effect .
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

[10][11]

Combinational risk

.If a COX-2 inhibitor is taken, one should not use a traditional NSAID (prescription or over-the-counter) concomitantly.^ NSAID medicines should only be used: .
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ One of the inaccuracies is quantification of NSAID use.
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

^ Consensus recommendations on the optimal use of COX-2 inhibitors and nonselective NSAIDs .
  • Updates on the management of upper gastrointestinal disorders in the primary care setting: NSAID-related gastropathies and pediatric reflux disease — The Journal of Family Practice 1 February 2010 3:33 UTC www.jfponline.com [Source type: Academic]

[12] .In addition, patients on daily aspirin therapy (e.g.^ Patients should be advised that if they experience a skin rash they should discontinue their NSAID and contact their physician for assessment and advice, including which additional therapies to discontinue.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ PPI therapy is believed to reduce the risk in all patients; the more risk factors present, the more cost-effective the additional therapy likely becomes.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

for reducing cardiovascular risk) need to be careful if they also use other .NSAIDs, as the latter may block the cardioprotective effects of aspirin.^ NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Aspirin - Aspirin is widely used for pain relief and has side effects and contraindications similar to those of NSAIDS. It is very important that people do not use aspirin and NSAIDs together unless directed by a physician.
  • Acetaminophen and NSAID Toxicity - Be Safe with Natural Cox 2 Inhibitors 1 February 2010 3:33 UTC www.qfac.com [Source type: Academic]

^ Aspirin is widely used for pain relief and has side effects and contraindications similar to those of NSAIDS. It is very important that people do not use aspirin and NSAIDs together unless directed by a physician.
  • Acetaminophen and NSAID Toxicity: Online References For Health Concerns 1 February 2010 3:33 UTC www.lef.org [Source type: Academic]

Cardiovascular

.A recent meta-analysis of all trials comparing NSAIDs found an 80% increase in the risk of myocardial infarction with both newer COX-2 antagonists and high dose traditional anti-inflammatories compared with placebo.^ Meta-analysis of randomised trials.
  • Use of Nonsteroidal Antiinflammatory Drugs: An Update for Clinicians: A Scientific Statement From the American Heart Association -- Antman et al. 115 (12): 1634 -- Circulation 11 January 2010 2:18 UTC circ.ahajournals.org [Source type: Academic]
  • Non-steroidal anti-inflammatory drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: results from a primary care based inception cohort of patients -- Goodson et al. 68 (3): 367 -- Annals of the Rheumatic Diseases 1 February 2010 3:33 UTC ard.bmj.com [Source type: Academic]
  • Cardiovascular Risks of Nonsteroidal Antiinflammatory Drugs in Patients After Hospitalization for Serious Coronary Heart Disease -- Ray et al. 2 (3): 155 -- Circulation: Cardiovascular Quality and Outcomes 1 February 2010 3:33 UTC circoutcomes.ahajournals.org [Source type: Academic]
  • BioMed Central | Full text | Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]
  • Updates on the management of upper gastrointestinal disorders in the primary care setting: NSAID-related gastropathies and pediatric reflux disease — The Journal of Family Practice 1 February 2010 3:33 UTC www.jfponline.com [Source type: Academic]
  • BioMed Central | Full text | Cyxlo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]

^ Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
  • Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs: A Nested Case-Control Study * Editorial Comment -- Bak et al. 34 (2): 379 -- Stroke 11 January 2010 2:18 UTC stroke.ahajournals.org [Source type: Academic]
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ The risk increases with increasing doses of NSAIDs.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

[13]
.NSAIDs aside from (low-dose) aspirin are associated with a doubled risk of symptomatic heart failure in patients without a history of cardiac disease.^ Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin Am J Gastroenterol.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]

^ The risk increases with increasing doses of NSAIDs.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

.In patients with such a history, however, use of NSAIDs (aside from low-dose aspirin) was associated with more than 10-fold increase in heart failure.^ Effects on concomitant use of low-dose aspirin .
  • Osteopathic Medicine and Primary Care | Full text | A review of the benefits and risks of nonsteroidal anti-inflammatory drugs in the management of mild-to-moderate osteoarthritis 11 January 2010 2:18 UTC www.om-pc.com [Source type: Academic]

^ Aspirin is an NSAID medicine but it does not increase the chance of a heart attack.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ Not surprisingly, NSAID use increases among the elderly.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

[14] .If this link is found to be causal, NSAIDs are estimated to be responsible for up to 20 percent of hospital admissions for congestive heart failure.^ The authors concluded that NSAIDs could account for approximately 20% of hospitalizations for congestive heart failure.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

^ NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year.
  • Back Pain and Sciatica 1 February 2010 3:33 UTC adam.about.com [Source type: Academic]

^ We thus assessed the cardiovascular safety of NSAIDs in patients recently hospitalized for serious coronary heart disease in a large multi-site retrospective cohort study.
  • Cardiovascular Risks of Nonsteroidal Antiinflammatory Drugs in Patients After Hospitalization for Serious Coronary Heart Disease -- Ray et al. 2 (3): 155 -- Circulation: Cardiovascular Quality and Outcomes 1 February 2010 3:33 UTC circoutcomes.ahajournals.org [Source type: Academic]

[14]

Gastrointestinal

.The main ADRs (adverse drug reactions) associated with use of NSAIDs relate to direct and indirect irritation of the gastrointestinal tract (GIT).^ Emergency admissions for upper gastrointestinal disease and their relation to NSAID use.
  • NSAIDs and adverse effects 1 February 2010 3:33 UTC www.medicine.ox.ac.uk [Source type: Academic]
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

^ Post-market Adverse Drug Reactions .
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Use of drugs to treat CVD comorbidity was inversely associated with NSAID use.
  • Non-steroidal anti-inflammatory drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: results from a primary care based inception cohort of patients -- Goodson et al. 68 (3): 367 -- Annals of the Rheumatic Diseases 1 February 2010 3:33 UTC ard.bmj.com [Source type: Academic]

.NSAIDs cause a dual insult on the GIT: the acidic molecules directly irritate the gastric mucosa, and inhibition of COX-1 reduces the levels of protective prostaglandins.^ COX-2 is also inhibited by selective NSAIDs.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

^ NSAID use can reduce inflammation by inhibiting COX-2 enzyme production.
  • Nonsteroidal Anti-inflammatory Drugs and Risk of Esophageal and Gastric Adenocarcinomas in Los Angeles County — Cancer Epidemiology, Biomarkers & Prevention 1 February 2010 3:33 UTC cebp.aacrjournals.org [Source type: Academic]

^ NSAIDs cause their gastric side effects by inhibiting the COX-1 enzyme.
  • Acetaminophen and NSAID Toxicity: Online References For Health Concerns 1 February 2010 3:33 UTC www.lef.org [Source type: Academic]

.Inhibition of prostaglandin synthesis in the GI tract causes increased gastric acid secretion, diminished bicarbonate secretion, diminished mucous secretion and diminished trophic effects on epithelial mucosa.^ This effect has been attributed to inhibition of renal prostaglandin synthesis by ibuprofen.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ The inhibition of acid secretion results in an increase of the gastric pH and a decrease of pepsin activity.

^ NSAIDs function by inhibiting prostaglandin synthesis.
  • NSAID's and increased blood pressure 1 February 2010 3:33 UTC www.lupusmctd.com [Source type: FILTERED WITH BAYES]

Common gastrointestinal ADRs include:[6]
.Risk of ulceration increases with duration of therapy, and with higher doses.^ Again, risk was greater at higher doses.
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

^ The risk may increase with duration of use.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ The risk increases with increasing doses of NSAIDs.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

.In attempting to minimise GI ADRs, it is prudent to use the lowest effective dose for the shortest period of time, a practice which studies show is not often followed.^ To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration .
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Use the lowest NSAID dose possible.
  • Back Pain and Sciatica 1 February 2010 3:33 UTC adam.about.com [Source type: Academic]

^ Avoid concurrent hepatotoxins if possible and use the lowest effective dose for the shortest duration.
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

.Recent studies show that over 50% of patients taking NSAIDs have sustained damage to their small intestine.^ NSAID and patients taking corticosteroids.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

^ Because there are usually no gastrointestinal symptoms from NSAIDs until bleeding begins, physicians cannot predict which patients taking these drugs will develop bleeding.
  • Back Pain and Sciatica 1 February 2010 3:33 UTC adam.about.com [Source type: Academic]

^ Some studies have reported a higher incidence of heart attacks in patients taking Vioxx compared to those taking standard NSAIDs.
  • Back Pain and Sciatica 1 February 2010 3:33 UTC adam.about.com [Source type: Academic]

[16]
.There are also some differences in the propensity of individual agents to cause gastrointestinal ADRs.^ Table 3 and Figure 3 do not consider that in all cases there was a statistically significant reduction in complicated gastrointestinal events, but no significant difference in cardiovascular events.
  • BioMed Central | Full text | Cyxlo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]

^ Both Helicobacter pylori and NSAIDs cause ulcers, so there may be some interactions.

^ Like aspirin Some Trade Names BAYER , these drugs can cause digestive upset, ulcers, and gastrointestinal bleeding.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

.Indomethacin, ketoprofen and piroxicam appear to have the highest prevalence of gastric ADRs, while ibuprofen (lower doses) and Diclofenac appear to have lower rates.^ Ibuprofen and diclofenac were classified as low risk; aspirin, sulindac, naproxen and indomethacin as moderate risk; and ketoprofen and piroxicam as high risk for GI side effects.
  • BioMed Central | Full text | Non-steroidal anti-inflammatory drugs cyclooxygenase-2 inhibitors and paracetamol use in Queensland and in the whole of Australia 11 January 2010 2:18 UTC www.biomedcentral.com [Source type: Academic]

^ Other less frequently used drugs included ketoprofen, indomethacin, piroxicam, meloxicam and nabumetone.
  • Non-steroidal anti-inflammatory drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: results from a primary care based inception cohort of patients -- Goodson et al. 68 (3): 367 -- Annals of the Rheumatic Diseases 1 February 2010 3:33 UTC ard.bmj.com [Source type: Academic]

^ The NSAIDs marketed in the United States in 1992 included diclofenac, diflunisal, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, mefenamic acid, nabumetone, naproxen, phenylbutazone, piroxicam, sulindac, and tolmetin.
  • A Study of Manufacturer - Supported Trials of Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Arthritis Reporting and Documentation of Efficacy and Toxicity 18 September 2009 7:52 UTC tobaccodocuments.org [Source type: Academic]
  • A Study of Manufacturer - Supported Trials of Nonsteroidal Anti-Inflammatory Drugs in the Treatment of Arthritis Reporting and Documentation of Efficacy and Toxicity 11 January 2010 2:18 UTC tobaccodocuments.org [Source type: Academic]

[6]
.Certain NSAIDs, such as aspirin, have been marketed in enteric-coated formulations which are claimed to reduce the incidence of gastrointestinal ADRs.^ Abajo FJ, Garcia Rodriguez LA. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ Abajo FJ, Garcia Rodriguez LA. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations BMC Clin Pharmacol.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]

^ The incidences of the three defects are higher in aspirin-treated animals than in non-aspirin NSAID-treated animals.
  • Arthritis Research & Therapy | Full text | Anti-inflammatory and immunosuppressive drugs and reproduction 11 January 2010 2:18 UTC arthritis-research.com [Source type: Academic]

.Similarly, there is a belief that rectal formulations may reduce gastrointestinal ADRs.^ Therefore, there may be contaminants and inconsistencies in formulation from manufacturer to manufacturer and also from batch to batch.
  • Georgetown University, Division of Comparative Medicine 1 February 2010 3:33 UTC www.dcm.georgetown.edu [Source type: Academic]

^ There are many potential mechanisms by which NSAIDs may reduce risk of colorectal cancer.
  • Risk of Microsatellite-Unstable Colorectal Cancer Is Associated Jointly with Smoking and Nonsteroidal Anti-inflammatory Drug Use -- Chia et al. 66 (13): 6877 -- Cancer Research 1 February 2010 3:33 UTC cancerres.aacrjournals.org [Source type: Academic]

^ The formulating of NSAIDs with zwitterionic phospholipids has also demonstrated pre-clinical efficacy with reduced gastrointestinal toxicity.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

.However, in consideration of the mechanism of such ADRs and indeed in clinical practice, these formulations have not been shown to have a reduced risk of GI ulceration.^ The risk associated with combination antiplatelet and anticoagulant therapies is substantial as well, and each is discussed below given their importance in cardiology clinical practice.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ Both celecoxib and rofecoxib have been shown in randomized clinical trials to decrease the risk of serious GI complications by 50% to 60% compared with traditional NSAIDs.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]

^ Thus, the selection of anti-inflammatory drug therapy in such patients must involve consideration of overall GI and cardiovascular risk of NSAIDs.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

[6]
.Commonly, gastrointestinal adverse effects can be reduced through suppressing acid production, by concomitant use of a proton pump inhibitor, e.g.^ PPI: proton pump inhibitor .
  • BioMed Central | Full text | Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]

^ The use of proton pump inhibitors in children: a comprehensive review.
  • Updates on the management of upper gastrointestinal disorders in the primary care setting: NSAID-related gastropathies and pediatric reflux disease — The Journal of Family Practice 1 February 2010 3:33 UTC www.jfponline.com [Source type: Academic]

^ Proton pump inhibitors.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]

.omeprazole, esomeprazole; or the prostaglandin analogue misoprostol.^ Misoprostol is a synthetic analogue of prostaglandin E 1 , a compound normally secreted by the gastric mucosa that is essential for protecting the gastric mucosa from chemical damage.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]

^ Clinical studies also support the efficacy of misoprostol (a synthetic prostaglandin E1 analogue) that reduces gastric acid secretion, as a strategy to prevent tNSAID-dependent gastropathy.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

.Misoprostol is itself associated with a high incidence of gastrointestinal ADRs (diarrhea).^ The primary purpose of this study was to examine the association between use of NSAIDs and breast cancer risk in a large prospective study of California educators with a high incidence of breast cancer ( 20 ) .
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

^ Use of , such as (Brand Name of Drug), is associated with an increased incidence of gastrointestinal adverse events (such as peptic/duodenal ulceration, perforation, obstruction and gastrointestinal bleeding).
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Gabriel SE, Jaakkimainen RL, Bombardier C. The cost-effectiveness of misoprostol for nonsteroidal antiinflammatory drug-associated adverse gastrointestinal events.
  • Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs: A Nested Case-Control Study * Editorial Comment -- Bak et al. 34 (2): 379 -- Stroke 11 January 2010 2:18 UTC stroke.ahajournals.org [Source type: Academic]
  • Unnecessary Prescribing of NSAIDs and the Management of NSAID-Related Gastropathy in Medical Practice 1 February 2010 3:33 UTC www.painstudy.com [Source type: Academic]

.While these techniques may be effective, they prove to be expensive for maintenance therapy.^ However, DERAMAXX tablets have been shown to be effective under both fed and fasted conditions; therefore, they may be administered in the fasted state if necessary.
  • VetRxDirect - Deramaxx (deracoxib): Chewable NSAID Tablets for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

^ In one distraction technique, people may learn to visualize themselves in a calm, comforting place (such as in a hammock or on a beach) when they feel pain.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

^ These events may occur at any time during therapy and without warning.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

Inflammatory bowel disease

.NSAIDs are never to be used 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.^ NSAIDs can cause stomach or intestinal bleeding.
  • Dolittler: On Metacam, Rimadyl, and their NSAID-ish side-effects 1 February 2010 3:33 UTC www.dolittler.com [Source type: General]

^ NSAIDs and aspirin cause gastric erosions which can become ulcers.

^ This review article explains that nonsteroidal anti-inflammatory drug (NSAID)-related toxicity involves not only the upper gastrointestinal tract, but also the large intestine, where it can manifest as diarrhea, colonic blood loss and anemia, strictures, ulcerations, perforations, worsening of inflammatory bowel disease and ulcerative colitis, and death.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

Pain relievers such as paracetamol or drugs containing codeine (which slows down bowel activity) are safer medications for pain relief in IBD.

Renal

.NSAIDs are also associated with a relatively high incidence of renal adverse drug reactions (ADRs).^ NSAIDs are associated with a number of adverse effects.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]
  • NSAIDs and adverse effects 1 February 2010 3:33 UTC www.medicine.ox.ac.uk [Source type: Academic]

^ Very rare adverse renal effects of NSAID therapy include nephritic syndrome and papillary necrosis.
  • NSAIDs, Coxibs, and Cardio-Renal Physiology: A Mechanism-Based Evaluation: Coxibs and Renal Physiology 1 February 2010 3:33 UTC cme.medscape.com [Source type: Academic]

^ Diclofenac-associated hepatotoxicity: analysis of 180 cases reported to the Food and Drug Administration as adverse reactions.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

.The mechanism of these renal ADRs is due to changes in renal haemodynamics (blood flow), ordinarily mediated by prostaglandins, which are affected by NSAIDs.^ Cyclooxygenase-2 inhibitors are a subclass of NSAIDs which specifically inhibit the production of compounds that mediate pain and inflammation via COX-2, while not affecting the production of gastroprotective prostaglandins through the action of cyclooxygenase-1.
  • Gastroprotective strategies among NSAID users 1 February 2010 3:33 UTC www.cfpc.ca [Source type: Academic]

^ In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ These effects are relatively mild and rare in healthy individuals but can be serious in patients whose renal function is prostaglandin-dependent.
  • NSAIDs, Coxibs, and Cardio-Renal Physiology: A Mechanism-Based Evaluation: Coxibs and Renal Physiology 1 February 2010 3:33 UTC cme.medscape.com [Source type: Academic]

Prostaglandins normally cause vasodilation of the afferent arterioles of the glomeruli. .This helps maintain normal glomerular perfusion and glomerular filtration rate (GFR), an indicator of renal function.^ Under these circumstances, renal prostaglandins help maintain renal perfusion and glomerular filtration rate ( GFR ).
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Half-life elimination: Normal renal function: 12-17 hours; End-stage renal disease: No change .
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ In addition, this vasodilatory PG increases renal blood flow and glomerular filtration rate (GFR) under conditions associated with decreased actual or effective circulating volume, resulting in greater tubular flow and secretion of potassium.
  • NSAIDs, Coxibs, and Cardio-Renal Physiology: A Mechanism-Based Evaluation: Coxibs and Renal Physiology 1 February 2010 3:33 UTC cme.medscape.com [Source type: Academic]

.This is particularly important in renal failure where the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II levels.^ Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE inhibitors , and angiotensin II receptor antagonists, and the elderly.
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ Combinations of ACE inhibitors, angiotensin-II antagonists, or diuretics with NSAIDs might have an increased risk for acute renal failure and hyperkalemia.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Consider monitoring serum creatinine levels after initiation of NSAID therapy in persons at risk of renal failure, and in those taking angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

.At these elevated levels, angiotensin II also constricts the afferent ateriole into the glomerulus in addition to the efferent arteriole one it normally constricts.^ Ibuprofen produced an elevation of plasma lithium levels and a reduction in renal lithium clearance in a study of eleven normal volunteers.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ These results support the notion that increased activation of mast cells rather than their increased number is responsible for elevated levels of mast cell tryptase.
  • Arch Dermatol -- Safety of Cyclooxygenase 2 Inhibitors and Increased Leukotriene Synthesis in Chronic Idiopathic Urticaria With Sensitivity to Nonsteroidal Anti-inflammatory Drugs, December 2003, Zembowicz et al. 139 (12): 1577 1 February 2010 3:33 UTC archderm.ama-assn.org [Source type: Academic]

^ Positive stool occult blood tests and elevated serum creatinine levels were also observed in these studies.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

.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.^ Because COX-2 is important for renal prostaglandin production, all NSAIDs (selective and nonselective) can cause volume-dependent renal failure, as well as renal failure from interstitial nephritis and nephritic syndrome.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

^ The blockade of prostaglandin synthesis by NSAID and the decreased activation of prostaglandin receptors cause reduced renal perfusion and oligo-hydramnios.
  • Arthritis Research & Therapy | Full text | Anti-inflammatory and immunosuppressive drugs and reproduction 11 January 2010 2:18 UTC arthritis-research.com [Source type: Academic]

^ NSAIDs also decrease prostaglandin-mediated blood flow to the kidneys, leading to an increased risk of renal failure in persons with cirrhosis.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

.Horses are particularly prone to these adverse affects compared to other domestic animal species.^ Also, studies in animals have shown that these medicines, if taken late in pregnancy, may increase the length of pregnancy, prolong labor, or cause other problems during delivery.
  • Drug Profiles: Nonsteroidal Anti-Inflammatory Drugs: NSAIDs 11 January 2010 2:18 UTC www.migraines.org [Source type: General]

^ NSAIDs have reached the market - more dogs are being adversely affected, and many dog owners never have been informed about the dangers of these drugs.
  • Dolittler: On Metacam, Rimadyl, and their NSAID-ish side-effects 1 February 2010 3:33 UTC www.dolittler.com [Source type: General]

^ In these analyses, naproxen stood out as being a unique NSAID in that its use was associated with reduced cardiovascular events compared with COX-2 inhibitors and other NSAIDs.
  • Arch Intern Med -- Selective Cyclooxygenase-2 Inhibition and Cardiovascular Effects: An Observational Study of a Medicaid Population, January 24, 2005, Shaya et al. 165 (2): 181 1 February 2010 3:33 UTC archinte.ama-assn.org [Source type: Academic]

Common ADRs associated with altered renal function include:[6]
  • Salt and fluid retention
  • Hypertension (high blood pressure)
.These agents may also cause renal impairment, especially in combination with other nephrotoxic agents.^ Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Most of these medicines, especially indomethacin and phenylbutazone, can cause serious side effects in any patient.
  • Drug Profiles: Nonsteroidal Anti-Inflammatory Drugs: NSAIDs 11 January 2010 2:18 UTC www.migraines.org [Source type: General]
  • Anti-inflammatory Drugs, Nonsteroidal (Systemic) 11 January 2010 2:18 UTC allnutritionals.com [Source type: General]

^ Meloxicam, like other drugs, may cause some side effects.
  • VetRxDirect - Metacam Oral Suspension NSAID Pain Reliever for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

.Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor and a diuretic - the so-called "triple whammy" effect.^ This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.
  • Flurbiprofen Official FDA information, side effects and uses. 18 September 2009 7:52 UTC www.drugs.com [Source type: Academic]
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors .
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

[17]
In rarer instances NSAIDs may also cause more severe renal conditions:[6]
.NSAIDs in combination with excessive use of phenacetin and/or paracetamol may lead to analgesic nephropathy.^ "Any NSAID" combines use of aspirin and ibuprofen.
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

^ Also, the elderly are more likely to have comorbid conditions such as osteoarthritis, which may be treated using prescribed or over-the-counter NSAIDs.
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

^ Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

[18]

Photosensitivity

.Photosensitivity is a commonly overlooked adverse effect of many of the NSAIDs.^ The aforementioned antineoplastic and anti-inflammatory effects of NSAIDs are commonly attributed to the inhibition of COX-2, the inducible form of COX ( 62 ).
  • Effects of Nonsteroidal Anti-Inflammatory Drugs on Helicobacter pylori-Infected Gastric Mucosae of Mice: Apoptosis, Cell Proliferation, and Inflammatory Activity -- Kim et al. 69 (8): 5056 -- Infection and Immunity 11 January 2010 2:18 UTC iai.asm.org [Source type: Academic]

^ We reviewed the prevalence, clinical spectrum, assessment, pathogenesis, and treatment of adverse effects of NSAIDs on the small intestine.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

^ The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of ibuprofen and aspirin is not generally recommended because of the potential for increased adverse effects.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

[19] .It is somewhat ironic that these anti-inflammatory agents may themselves produce inflammation in combination with exposure to sunlight.^ Vancomycin: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Vancomycin.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ These are ALL natural anti-inflammatories: .
  • Fibroid Remedies on Earth Clinic, like Apple Cider Vinegar, Blackstrap Molasses and more. 11 January 2010 2:18 UTC www.earthclinic.com [Source type: Original source]

^ Methotrexate: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Methotrexate.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

.The 2-arylpropionic acids have proven to be the most likely to produce photosensitivity reactions, but other NSAIDs have also been implicated including piroxicam, diclofenac and benzydamine.^ Acetylsalicylic acid (ASA) or other NSAIDs : .
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Other NSAIDs, including piroxicam, ibuprofen, and sulindac had less of an effect.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Acetylsalicylic Acid ( ASA ) or other NSAIDs e.g.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

.Benoxaprofen, since withdrawn due to its hepatotoxicity, was the most photoactive NSAID observed.^ I think ultimately she and most vets come down on the side of feeling that the benefits outweigh the risks, but personally, ever since then I won't give an NSAID to any of my pets.
  • Dolittler: On Metacam, Rimadyl, and their NSAID-ish side-effects 1 February 2010 3:33 UTC www.dolittler.com [Source type: General]

^ I know how damaging NSAIDS can be, having read the account of one man with AS who has had to have most of his stomach removed due to them.
  • Ditch your NSAID meds | The Blog of Michael R. Eades, M.D. 1 February 2010 3:33 UTC www.proteinpower.com [Source type: General]

.The mechanism of photosensitivity, responsible for the high photoactivity of the 2-arylpropionic acids, is the ready decarboxylation of the carboxylic acid moiety.^ High- versus standard-dose ranitidine for control of heartburn in poorly responsive acid reflux disease: A prospective, controlled trial.

.The specific absorbance characteristics of the different chromophoric 2-aryl substituents, affects the decarboxylation mechanism.^ A more detailed understanding of the tissue-specific effects of NSAIDs, particularly in the context of the complex biological mechanisms involved in the development of different cancers, is also needed.
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

While ibuprofen is somewhat of an exception, having weak absorption, it has been reported to be a weak photosensitising agent.

During pregnancy

.NSAIDs are not recommended during pregnancy, particularly during the third trimester.^ (Brand Name of Drug) is CONTRAINDICATED for use during the third trimester of pregnancy because of risk of premature closure of the ductus arteriosus and the potential to prolong parturition (see Toxicology).
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ It is not recommended for use during the last 3 months of pregnancy due to the potential for harm to an unborn baby and interference with normal labor/delivery.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ It is not recommended for use during the last 3 months of pregnancy due to possible harm to an unborn baby.
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

.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.^ In late pregnancy, as with other NSAIDs, MOTRIN tablets should be avoided because it may cause premature closure of the ductus arteriosus .
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ As a class, NSAIDs may be associated with gastrointestinal, renal and hepatic toxicity.
  • VetRxDirect - Deramaxx (deracoxib): Chewable NSAID Tablets for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

^ In late pregnancy, as with other NSAIDs, MOTRIN tablets should be avoided because it may cause premature closure of the ductus arteriosus.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

Additionally, they are linked with premature birth.[20] .Aspirin, however, is used together with heparin in pregnant women with antiphospholipid antibodies.^ The use of (Brand Name of Drug) is not recommended in women trying to get pregnant.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ We used a likelihood ratio test to evaluate homogeneity of the relative risk estimates when we compared women who used only ibuprofen with women who used aspirin infrequently (with ibuprofen) and with women who used aspirin daily (with ibuprofen) (2 df ).
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

^ Aspirin-The chance of serious side effects may be increased if aspirin is used together with a nonsteroidal anti-inflammatory drug on a regular basis .
  • Anti-inflammatory Drugs, Nonsteroidal (Systemic) 11 January 2010 2:18 UTC allnutritionals.com [Source type: General]

[21]
.In contrast, paracetamol (acetaminophen) is regarded as being safe and well-tolerated during pregnancy.^ MTX is contraindicated during pregnancy and should be prescribed to fertile women only under the cover of safe contraception (evidence level III).
  • Arthritis Research & Therapy | Full text | Anti-inflammatory and immunosuppressive drugs and reproduction 11 January 2010 2:18 UTC arthritis-research.com [Source type: Academic]

^ This class of drugs is uniformly safe and well tolerated, although the risk of adverse effects is slightly increased with cimetidine because it interacts with cytochrome P-450, causing increased drug-drug interactions.

^ Short-term use (5–10 days) of over-the-counter tNSAIDs has been shown in several studies to be extremely safe and well tolerated.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

[22] .Doses should be taken as prescribed, due to risk of hepatotoxicity with overdoses.^ The risk is higher when higher doses are taken and when the drug is taken for a longer time.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

^ The actual dose to be given should be prescribed by the veterinarian.
  • VetRxDirect - Metacam Oral Suspension NSAID Pain Reliever for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

^ The CHMP recommended that warnings of a possible risk when high doses are taken for long periods should be added to the prescribing information.
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

[23]
.In France, the country's health agency contraindicates the use of NSAIDs, including aspirin, after the sixth month of pregnancy.^ "Any NSAID" combines use of aspirin and ibuprofen.
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

^ It is not recommended for use during the last 3 months of pregnancy due to the potential for harm to an unborn baby and interference with normal labor/delivery.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use.
  • JAMA -- Abstract: Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis: The CLASS Study: A Randomized Controlled Trial, September 13, 2000, Silverstein et al. 284 (10): 1247 11 January 2010 2:18 UTC jama.ama-assn.org [Source type: Academic]

[24]

Other

.Common ADRs, other than listed above, include: raised liver enzymes, headache, dizziness.^ As with other NSAIDs , borderline elevations of one or more liver enzyme tests ( AST , ALT , alkaline phosphatase) may occur in up to 15% of patients.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Drugs other than those listed here may also interact with gabapentin or affect your condition.
  • NSAID's and increased blood pressure 1 February 2010 3:33 UTC www.lupusmctd.com [Source type: FILTERED WITH BAYES]

^ Gabapentin may also be used for purposes other than those listed in this medication guide.
  • NSAID's and increased blood pressure 1 February 2010 3:33 UTC www.lupusmctd.com [Source type: FILTERED WITH BAYES]

[6] .Uncommon ADRs include: hyperkalaemia, confusion, bronchospasm, rash.^ Other uncommon but potential adverse effects include confusion, depression, dizziness, and somnolence.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

[6] .Rapid and severe swelling of the face and/or body.^ Swelling of face, hands, feet, or lower legs; weight gain (rapid).
  • Anti-inflammatory Drugs, Nonsteroidal (Systemic) 11 January 2010 2:18 UTC allnutritionals.com [Source type: General]

.Ibuprofen may also rarely cause irritable bowel syndrome symptoms.^ This drug may rarely cause serious liver disease.
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ Keating JP, Rees M. Diaphragm disease: a rare cause of small-bowel obstruction.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

^ IBUPROFEN - ORAL (eye-byou-PRO-fen) COMMON BRAND NAME(S): Advil, Motrin, Nuprin WARNING: This drug may infrequently cause serious (rarely fatal) bleeding from the stomach or intestines.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

.Most NSAIDs penetrate poorly into the central nervous system (CNS).^ Central nervous system: Headache, pain .
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Central nervous system: Dizziness, hypaesthesia .
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ Most NSAID are excreted in very small quantities into human breast milk [ 41 , 42 ].
  • Arthritis Research & Therapy | Full text | Anti-inflammatory and immunosuppressive drugs and reproduction 11 January 2010 2:18 UTC arthritis-research.com [Source type: Academic]

.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.^ Gabapentin may cause dizziness or drowsiness.
  • NSAID's and increased blood pressure 1 February 2010 3:33 UTC www.lupusmctd.com [Source type: FILTERED WITH BAYES]

^ Along with its needed effects, a medicine may cause some unwanted effects.
  • Anti-inflammatory Drugs, Nonsteroidal (Systemic) 11 January 2010 2:18 UTC allnutritionals.com [Source type: General]

^ Cyclooxygenase-1 (COX-1) is the enzyme responsible for facilitating constitutive physiological processes (e.g., platelet aggregation, gastric mucosal protection, renal perfusion).
  • VetRxDirect - Deramaxx (deracoxib): Chewable NSAID Tablets for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

.In very rare cases, ibuprofen can cause aseptic meningitis.^ Ibuprofen-induced aseptic meningitis in rheumatoid arthritis.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

^ Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen therapy.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ Aseptic meningitis occurs more often in persons with lupus who are taking ibuprofen or naproxen, but it should be considered in any adult with meningitis who is taking NSAIDs.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

.As with other drugs, allergies to NSAIDs exist.^ PRECAUTIONS: Before taking ibuprofen, tell your doctor or pharmacist if you are allergic to it; or to aspirin or other NSAIDs (e.g., naproxen, celecoxib); or if you have any other allergies.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ Indeed, NSAIDS are the most common cause of drug-related morbidity and mortality reported to the FDA and other regulatory agencies around the world.
  • Ditch your NSAID meds | The Blog of Michael R. Eades, M.D. 1 February 2010 3:33 UTC www.proteinpower.com [Source type: General]
  • Michael R. Eades, M.D.: Ditch your NSAID meds 1 February 2010 3:33 UTC www.proteinpower.com [Source type: General]

^ Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis, rheumatoid arthritis, and other painful conditions.
  • NSAIDs, Coxibs, and Cardio-Renal Physiology: A Mechanism-Based Evaluation: Coxibs and Renal Physiology 1 February 2010 3:33 UTC cme.medscape.com [Source type: Academic]

.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.^ People may respond to one antidepressant and not others.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

^ Many other traditional NSAIDs may also be associated with a small increased risk of thrombotic events.
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

^ Some patients may also experience an increase in symptoms of gastroesophageal reflux disease on NSAIDs as well ( 23 ).
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]

[25]

Chirality

.Most NSAIDs are chiral molecules (diclofenac is a notable exception).^ Certain NSAIDs, including most notably piroxicam, can cause increased sensitivity to the sun, amplifying the risk of sunburn or skin rash.
  • Nonsteroidal Anti-inflammatory Drugs | Lifescript.com 11 January 2010 2:18 UTC www.lifescript.com [Source type: Academic]
  • Natural & Alternative Treatments - Hartford Hospital, Connecticut 11 January 2010 2:18 UTC www.harthosp.org [Source type: Academic]

^ The four most commonly prescribed NSAIDs were naproxen (25% of NSAID prescriptions), diclofenac (20.8%), ketoprofen (16.7%), and tiaprofenic acid (12.5%).
  • Unnecessary Prescribing of NSAIDs and the Management of NSAID-Related Gastropathy in Medical Practice — Ann Intern Med 1 February 2010 3:33 UTC www.annals.org [Source type: Academic]

However, the majority are prepared in a racemic mixture. Typically, only a single enantiomer is pharmacologically active. .For some drugs (typically profens), an isomerase enzyme exists in vivo which converts the inactive enantiomer into the active form, although its activity varies widely in individuals.^ The fetal liver lacks the enzyme inosinatopyrophosphorylase, which converts azathioprine to its active form and therefore should be theoretically protected from azathioprine crossing the placenta [ 125 ].
  • Arthritis Research & Therapy | Full text | Anti-inflammatory and immunosuppressive drugs and reproduction 11 January 2010 2:18 UTC arthritis-research.com [Source type: Academic]

^ The synergistic effect of the combination and the resulting decrease in the need for each individual agent may obviate some of the adverse effects of each drug when taken alone.
  • Arch Otolaryngol Head Neck Surg -- Postoperative Hemorrhage With Nonsteroidal Anti-inflammatory Drug Use After Tonsillectomy: A Meta-analysis, October 2003, Krishna et al. 129 (10): 1086 11 January 2010 2:18 UTC archotol.ama-assn.org [Source type: Academic]

^ Their anti-inflammatory effect is due to an inhibition of the cyclooxygenases (COX-1 and -2), which convert arachidonic acid into biologically active PGs.
  • Comparative Effects of the Nonsteroidal Anti-inflammatory Drug Nepafenac on Corneal Sensory Nerve Fibers Responding to Chemical Irritation -- Acosta et al. 48 (1): 182 -- Investigative Ophthalmology & Visual Science 11 January 2010 2:18 UTC www.iovs.org [Source type: Academic]

.This phenomenon is likely to be 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.^ The relationship between variables was studied by Pearson and Spearman correlation analysis.
  • Arch Dermatol -- Safety of Cyclooxygenase 2 Inhibitors and Increased Leukotriene Synthesis in Chronic Idiopathic Urticaria With Sensitivity to Nonsteroidal Anti-inflammatory Drugs, December 2003, Zembowicz et al. 139 (12): 1577 1 February 2010 3:33 UTC archderm.ama-assn.org [Source type: Academic]

^ We thus performed a new-user analysis that excluded prevalent users of individual NSAIDs ( Table 2 ).
  • Cardiovascular Risks of Nonsteroidal Antiinflammatory Drugs in Patients After Hospitalization for Serious Coronary Heart Disease -- Ray et al. 2 (3): 155 -- Circulation: Cardiovascular Quality and Outcomes 1 February 2010 3:33 UTC circoutcomes.ahajournals.org [Source type: Academic]

^ The finding is similar to a previous study by Thrift et al 12 that examined the association between use of aspirin or other NSAIDs and ICH using a case-control study.
  • Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs: A Nested Case-Control Study * Editorial Comment -- Bak et al. 34 (2): 379 -- Stroke 11 January 2010 2:18 UTC stroke.ahajournals.org [Source type: Academic]

.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.^ Topical preparations should produce fewer side effects and so could be a good alternative treatment for this group of people.
  • Topical NSAID As Effective As Tablets For Knee Pain 1 February 2010 3:33 UTC www.medicalnewstoday.com [Source type: Academic]

^ As you can see, despite these drugs being available over the counter, they are not without the potential for serious side effects.
  • Ditch your NSAID meds | The Blog of Michael R. Eades, M.D. 1 February 2010 3:33 UTC www.proteinpower.com [Source type: General]

^ If taken for a long time, nonsteroidal anti-inflammatory drugs, including those available without a prescription, can have serious side effects.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

Naproxen has always been marketed as the single active enantiomer.

Selective COX inhibitors

COX-2 inhibitors

.The discovery of COX-2 in 1991 by Daniel L. Simmons at Brigham Young University raised the hope of developing an effective NSAID without the gastric problems characteristic of these agents.^ Pre-clinical studies of highly selective COX-2 inhibitors in animal models suggest that these agents may reduce gastric toxicity compared to non-selective NSAIDs.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

^ Because coxibs block mainly COX-2 enzymes, they are less likely to cause these problems.
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

^ Therefore, selective COX-2 inhibitors were developed to reduce the side effects of classic NSAIDs.
  • Development of Nonsteroidal Anti-Inflammatory Drug Analogs and Steroid Carboxylates Selective for Human Aldo-Keto Reductase Isoforms: Potential Antineoplastic Agents That Work Independently of Cyclooxygenase Isozymes — Molecular Pharmacology 11 January 2010 2:18 UTC molpharm.aspetjournals.org [Source type: Academic]

.It was thought that selective inhibition of COX-2 would result in anti-inflammatory action without disrupting gastroprotective prostaglandins.^ COX-2 is also inhibited by selective NSAIDs.
  • NSAID Prescribing Precautions - December 15, 2009 - American Family Physician 1 February 2010 3:33 UTC www.aafp.org [Source type: Academic]

^ The mechanism of action of Flurbiprofen tablet, USP, like that of other nonsteroidal anti-inflammatory drugs, is not completely understood but may be related to prostaglandin synthetase inhibition.
  • Flurbiprofen Official FDA information, side effects and uses. 18 September 2009 7:52 UTC www.drugs.com [Source type: Academic]

^ Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties .
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

.COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes.^ This enzyme exists in at least 2 isoforms: COX-1, which participates to the homeostatic regulation of many tissues and produces protective prostaglandines in the stomach, and COX-2, involved in the formation of mediators of pain and inflammation.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

^ COX-1 is constitutively expressed in renal vasculature, glomerular mesangial cells, and both cortical and medullar portions of the collecting duct (Figure 5).
  • NSAIDs, Coxibs, and Cardio-Renal Physiology: A Mechanism-Based Evaluation: Coxibs and Renal Physiology 1 February 2010 3:33 UTC cme.medscape.com [Source type: Academic]

^ Describe the role of prostaglandins and cyclooxygenase in physiologic and pathophysiologic processes.
  • NSAIDs, Coxibs, and Cardio-Renal Physiology: A Mechanism-Based Evaluation: Coxibs and Renal Physiology 1 February 2010 3:33 UTC cme.medscape.com [Source type: Academic]

.One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid.^ Inhibition of the COX-1 pathway blocks production of prostaglandins that play an important protective role in the stomach by increasing mucosal blood flow and stimulating the synthesis and secretion of mucus and bicarbonate, as well as promoting epithelial proliferation.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ Prostaglandins have many functions in the body, including inducing pain, protecting the lining of the stomach from acid, and regulating the tone of blood vessels.
  • NSAID's and increased blood pressure 1 February 2010 3:33 UTC www.lupusmctd.com [Source type: FILTERED WITH BAYES]

^ Prostaglandins are potent lipid mediators derived from arachidonic acid and have an important role in regulating the development of colitis in IL-10-deficient mice.
  • 5-Lipoxygenase-derived lipid mediators are not required for the development of NSAID-induced inflammatory bowel disease in IL-10-/- mice -- Narushima et al. 294 (2): G477 -- AJP - Gastrointestinal and Liver Physiology 1 February 2010 3:33 UTC ajpgi.physiology.org [Source type: Academic]

.When non-selective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, these protective effects are lost and ulcers of the stomach or duodenum and potentially internal bleeding can result.^ Effect of aspirin on ulcer site blood flow in cat stomachs.
  • ICAM-1 and P-selectin expression in a model of NSAID-induced gastropathy -- Morise et al. 274 (2): 246 -- AJP - Gastrointestinal and Liver Physiology 1 February 2010 3:33 UTC ajpgi.physiology.org [Source type: Academic]

^ The gastrointestinal effects of nonselective NSAIDs and COX-2-selective inhibitors.
  • NSAID-Induced Acute Phase Response is Due to Increased Intestinal Permeability and Characterized by Early and Consistent Alterations in Hepatic Gene Expression -- Tugendreich et al. 34 (2): 168 -- Toxicologic Pathology 1 February 2010 3:33 UTC tpx.sagepub.com [Source type: Academic]

^ Effects of COX inhibitors on biofilm formation.
  • Effects of Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs on Biofilms and Planktonic Cells of Candida albicans -- Alem and Douglas 48 (1): 41 -- Antimicrobial Agents and Chemotherapy 11 January 2010 2:18 UTC aac.asm.org [Source type: Academic]

.COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.^ NSAIDs reduce pain and inflammation by inhibiting the enzyme cyclooxygenase.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

^ Aspirin and other NSAIDs inhibit the expression of the cyclooxygenase 2 (COX-2) gene, which encodes one of two cyclooxygenase enzymes that catalyzes the synthesis of prostaglandins from the dietary fatty acid arachidonic acid.
  • Nonsteroidal Anti-Inflammatory Drug Use and Breast Cancer Risk by Stage and Hormone Receptor Status -- Marshall et al. 97 (11): 805 -- JNCI Journal of the National Cancer Institute 1 February 2010 3:33 UTC jnci.oxfordjournals.org [Source type: Academic]

^ This enzyme exists in at least 2 isoforms: COX-1, which participates to the homeostatic regulation of many tissues and produces protective prostaglandines in the stomach, and COX-2, involved in the formation of mediators of pain and inflammation.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

.The relatively selective COX-2 inhibiting oxicam, meloxicam, was the first step towards developing a true COX-2 selective inhibitor.^ Selective COX-2 inhibitor are a subclass of the "traditional" .
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Other selective COX-2 inhibitors (ie.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

^ Event numbers and person-years of exposure, with corresponding mean annual event rates in parentheses, are presented for patients allocated to selective COX-2 inhibitor or placebo.
  • Use of Nonsteroidal Antiinflammatory Drugs: An Update for Clinicians: A Scientific Statement From the American Heart Association -- Antman et al. 115 (12): 1634 -- Circulation 11 January 2010 2:18 UTC circ.ahajournals.org [Source type: Academic]

.Coxibs, the newest class of NSAIDs, can be considered as true COX-2 selective inhibitors, and include celecoxib, rofecoxib, valdecoxib, parecoxib and etoricoxib.^ Coxib: cyclooxygenase-2 selective inhibitor .
  • BioMed Central | Full text | Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: review of clinical trials and clinical practice 1 February 2010 3:33 UTC www.biomedcentral.com [Source type: Academic]

^ The gastrointestinal effects of nonselective NSAIDs and COX-2-selective inhibitors.
  • NSAID-Induced Acute Phase Response is Due to Increased Intestinal Permeability and Characterized by Early and Consistent Alterations in Hepatic Gene Expression -- Tugendreich et al. 34 (2): 168 -- Toxicologic Pathology 1 February 2010 3:33 UTC tpx.sagepub.com [Source type: Academic]

^ NSAID/COX-2 inhibitor and dose to be prescribed .
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

Controversies with COX-2 inhibitors

.While it was hoped that this COX-2 selectivity would reduce gastrointestinal adverse drug reactions (ADRs), there is little conclusive evidence that this is true.^ Post-market Adverse Drug Reactions .
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Diclofenac-associated hepatotoxicity: analysis of 180 cases reported to the Food and Drug Administration as adverse reactions.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

^ No, next to the “Post comment” button there will be an option to “Tweet this comment”, select this option if you would like your comment posted to your Twitter account as well.
  • Nonsteroidal Anti-inflammatory Drugs | Lifescript.com 11 January 2010 2:18 UTC www.lifescript.com [Source type: Academic]

.The original study touted by Searle (now part of Pfizer), showing a reduced rate of ADRs for celecoxib, was later revealed to be based on preliminary data - the final data showed no significant difference in ADRs when compared with diclofenac.^ Similarly, another long-term clinical study, the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), showed no significant differences between aspirin users and nonusers in the incidence of serious GI events among patients treated with a COX-2 inhibitor (lumiracoxib) or an NSAID (naproxen or ibuprofen).

^ In patients with a history of ulcer bleeding, a recent RCT reported no significant difference in the rate of recurrent bleeding at 6 months across patient groups (4.9% with celecoxib vs 6.4% diclofenac and omeprazole).
  • Updates on the management of upper gastrointestinal disorders in the primary care setting: NSAID-related gastropathies and pediatric reflux disease — The Journal of Family Practice 1 February 2010 3:33 UTC www.jfponline.com [Source type: Academic]

^ Although mean impulse frequency was slightly reduced 1 minute after drug application, differences with the control were not significant ( Fig.
  • Comparative Effects of the Nonsteroidal Anti-inflammatory Drug Nepafenac on Corneal Sensory Nerve Fibers Responding to Chemical Irritation -- Acosta et al. 48 (1): 182 -- Investigative Ophthalmology & Visual Science 11 January 2010 2:18 UTC www.iovs.org [Source type: Academic]

.Rofecoxib however, which has since been withdrawn, had been shown to produce significantly fewer gastrointestinal ADRs compared to naproxen.^ Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis: VIGOR Study Group N Engl J Med.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Bhatt et al. 52 (18): 1502 -- Journal of the American College of Cardiology 1 February 2010 3:33 UTC content.onlinejacc.org [Source type: Academic]

^ However, they do increase cardiovascular risk compared with ibuoprofen 1200mg per day or less, or naproxen 1000mg per day (see MeReC Extra 30) .
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

^ In two large comparative prospective trials (MELISSA and SELECT) meloxicam had significantly less gastrointestinal toxicity than non-selective NSAIDs in osteoarthritis patients.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

[26] .This study, the VIGOR trial, raised the issue of the cardiovascular safety of the coxibs - a statistically insignificant increase in the incidence of myocardial infarctions was observed in patients on rofecoxib.^ One study enrolled only patients with myocardial infarction.
  • eMJA: Risk of serious NSAID-related gastrointestinal events during long-term exposure: a systematic review 1 February 2010 3:33 UTC www.mja.com.au [Source type: Academic]

^ NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal.
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ In the APPROVe trial, rofecoxib increased the risk of the combined primary endpoint (stroke, myocardial infarction [MI] or death) from soon after treatment was started until a year after it was stopped.
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

Further data, from the APPROVe trial, showed a relative risk of cardiovascular events of 1.97 versus placebo - a result which resulted in the worldwide withdrawal of rofecoxib in October 2004.

COX-3 inhibitors

.Simmons also co-discovered COX-3 in 2002 and analyzed this new isozyme's relation to paracetamol (acetaminophen), arguably the most widely used analgesic drug in the world.^ Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ In over 10% of patients the nephropathy was judged to be related to the use of these drugs.
  • COMPLICATIONS DUE TO NSAIDS 1 February 2010 3:33 UTC www.garynull.com [Source type: Academic]

^ Most nonopioid analgesics are classified as nonsteroidal anti-inflammatory drugs (NSAIDs).
  • Treatment: Pain: Merck Manual Home Edition 18 September 2009 7:52 UTC www.merck.com [Source type: FILTERED WITH BAYES]

[27] .The authors postulated that inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.^ COX-2 inhibitors may have a place for high risk patients who could not take anti-ulcer co-therapy and possibly also for patients who have intolerance to tNSAIDs.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ The most commonly described mechanism involves the ability of NSAIDs to inhibit COX activity, thereby depressing prostaglandin synthesis ( 39 , 51 ).
  • Risk of Microsatellite-Unstable Colorectal Cancer Is Associated Jointly with Smoking and Nonsteroidal Anti-inflammatory Drug Use -- Chia et al. 66 (13): 6877 -- Cancer Research 1 February 2010 3:33 UTC cancerres.aacrjournals.org [Source type: Academic]

^ Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, fever, and inflammation.
  • Nonsteroidal Anti-inflammatory Drugs | Lifescript.com 11 January 2010 2:18 UTC www.lifescript.com [Source type: Academic]

.The relevance of this research has been called into question as the putative COX-3 gene encodes proteins with completely different amino acid sequences than COX-1 or COX-2. The expressed proteins do not show COX activity and it is unlikely that they play a role in prostaglandin mediated physiological responses.^ Inhibition of the COX-1 pathway blocks production of prostaglandins that play an important protective role in the stomach by increasing mucosal blood flow and stimulating the synthesis and secretion of mucus and bicarbonate, as well as promoting epithelial proliferation.
  • ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents -- Writing Committee Members et al. 118 (18): 1894 -- Circulation 1 February 2010 3:33 UTC circ.ahajournals.org [Source type: Academic]

^ COX-1 is expressed in most tissues of the body and largely governs the homeostatic production of arachidonic acid metabolites necessary to maintain physiologic integrity, including gastric cytoprotection via prostacyclin (PGI 2 ), whereas COX-2 is induced in response to inflammatory stimuli and is responsible for the enhanced production of eicosanoid mediators for inflammation and pain.
  • An Evidence-Based Update on Nonsteroidal Anti-Inflammatory Drugs -- Ong et al. 5 (1): 19 -- Clinical Medicine & Research 11 January 2010 2:18 UTC www.clinmedres.org [Source type: Academic]

^ Cyclooxygenase-1 (COX-1) is the enzyme responsible for facilitating constitutive physiological processes (e.g., platelet aggregation, gastric mucosal protection, renal perfusion).
  • VetRxDirect - Deramaxx (deracoxib): Chewable NSAID Tablets for Dogs 1 February 2010 3:33 UTC www.vetrxdirect.com [Source type: FILTERED WITH BAYES]

[28]

Veterinary use

.Research supports the use of NSAIDs for the control of pain associated with veterinary procedures such as dehorning and castration of calves.^ Also, the elderly are more likely to have comorbid conditions such as osteoarthritis, which may be treated using prescribed or over-the-counter NSAIDs.
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

^ Multiple logistic regression was used to examine the independent associations between treatment of H pylori , and counseling about NSAID use on the outcomes of interest.
  • JAMA -- Process of Care and Outcomes for Elderly Patients Hospitalized With Peptic Ulcer Disease: Results From a Quality Improvement Project, October 24, 2001, Brock et al. 286 (16): 1985 1 February 2010 3:33 UTC jama.ama-assn.org [Source type: Academic]

^ Keating JP, McIlwaine J. Simultaneous small and large bowel ulceration associated with short term NSAID use.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

.The best effect is obtained by combining a short-term local anesthetic such as lidocaine with an NSAID acting as a longer term analgesic.^ Blood Pressure: In short-term use, NSAIDs vary considerably in their effect on blood pressure.
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Naproxen: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]
  • Diclofenac: Drug Information Provided by Lexi-Comp: Merck Manual Professional 1 February 2010 3:33 UTC www.merck.com [Source type: Academic]

^ The exception is the use of low dose ASA for cardiovascular protection, when another NSAID is being used for its analgesic/anti-inflammatory effect, keeping in mind that combination NSAID therapy is associated with additive adverse reactions.
  • Guidance Document: Basic Product Monograph Information for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 1 February 2010 3:33 UTC www.hc-sc.gc.ca [Source type: Academic]

^ Chronic renal papillary necrosis is associated with long-term use of multiple high doses of a single analgesic or combinations of analgesics.
  • NSAIDs, Coxibs, and Cardio-Renal Physiology: A Mechanism-Based Evaluation: Coxibs and Renal Physiology 1 February 2010 3:33 UTC cme.medscape.com [Source type: Academic]

.However, most of the existing research data relates to ketoprofen while the only NSAID currently available for labelled use in the United States is flunixin meglumine, indicated for conditions other than post-operative pain.^ NSAID medicines should only be used: .
  • Motrin (Ibuprofen) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]
  • Mobic (Meloxicam) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList 1 February 2010 3:33 UTC www.rxlist.com [Source type: Academic]

^ The available permeability data use indomethacin or naproxen as prototypical NSAIDs.
  • Detection and Prevention of NSAID-Induced Enteropathy 1 February 2010 3:33 UTC www.ualberta.ca [Source type: Academic]

^ Posted in Musculoskeletal Pain , Other therapeutics , Pain .
  • Musculoskeletal Pain « NPCi blog 1 February 2010 3:33 UTC www.npci.org.uk [Source type: Academic]

References

  1. ^ http://www.drugbank.ca/cgi-bin/getCard.cgi?CARD=APRD00372 Drugbank Card for Ibuprofen
  2. ^ http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm
  3. ^ http://www.fda.gov/cder/drug/infopage/celebrex/celebrex-hcp.htm FDA Alert for Practitioners on Celebrex (celecoxib)
  4. ^ http://www.fda.gov/cder/drug/infopage/vioxx/PHA_vioxx.htm
  5. ^ http://www.fda.gov/cder/drug/InfoSheets/HCP/valdecoxibHCP.htm Alert for Healthcare Professionals: Valdecoxib (marketed as Bextra)
  6. ^ a b c d e f g h Simone Rossi, ed (2006). Australian medicines handbook 2006. Adelaide: Australian Medicines Handbook Pty Ltd. ISBN 0-9757919-2-3.  
  7. ^ Gøtzsche, Pc (March 1989). "Methodology and overt and hidden bias in reports of 196 double-blind trials of nonsteroidal antiinflammatory drugs in rheumatoid arthritis". Controlled clinical trials 10 (1): 31–56. doi:10.1016/0197-2456(89)90017-2. ISSN 0197-2456. PMID 2702836.  
  8. ^ a b Green, Ga (2001). "Understanding NSAIDs: from aspirin to COX-2". Clinical cornerstone 3 (5): 50–60. doi:10.1016/S1098-3597(01)90069-9. ISSN 1098-3597. PMID 11464731.  
  9. ^ Chan, Gc; Hinds, Tr; Impey, S; Storm, Dr (15 July 1998). "Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol" (Free full text). The Journal of neuroscience : the official journal of the Society for Neuroscience 18 (14): 5322–32. ISSN 0270-6474. PMID 9651215. http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=9651215.  
  10. ^ Bayer HealthCare Pharmaceuticals Inc (September 2008). "CIPRO (ciprofloxacin hydrochloride) TABLETS CIPRO,(ciprofloxacin*) ORAL SUSPENSION" (PDF). USA: FDA. http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019537s68,19847s42,19857s49,20780s26,21473s24lbl.pdf. Retrieved 31 August 2009.  
  11. ^ Royal Pharmaceutical Society of Great Britain (2009). "5 Infections". British National Formulary (BNF 57). BMJ Group and RPS Publishing. ISBN 9780853698456.  
  12. ^ http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=398&topcategory=About
  13. ^ Kearney, Pm; Baigent, C; Godwin, J; Halls, H; Emberson, Jr; Patrono, C (June 2006). "Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials" (Free full text). BMJ (Clinical research ed.) 332 (7553): 1302–8. doi:10.1136/bmj.332.7553.1302. ISSN 0959-8138. PMID 16740558. PMC 1473048. http://bmj.com/cgi/pmidlookup?view=long&pmid=16740558.  
  14. ^ a b Page, J; Henry, D (March 2000). "Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underrecognized public health problem" (Free full text). Archives of internal medicine 160 (6): 777–84. doi:10.1001/archinte.160.6.777. ISSN 0003-9926. PMID 10737277. http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=10737277.  
  15. ^ Traversa, G; Walker, Am; Ippolito, Fm; Caffari, B; Capurso, L; Dezi, A; Koch, M; Maggini, M; Alegiani, Ss; Raschetti, R (January 1995). "Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs". Epidemiology (Cambridge, Mass.) 6 (1): 49–54. doi:10.1097/00001648-199501000-00010. ISSN 1044-3983. PMID 7888445.  
  16. ^ Higuchi K, Umegaki E, Watanabe T, Yoda Y, Morita E, Murano M, Tokioka S, Arakawa T (July 2009). "Present status and strategy of NSAIDs-induced small bowel injury". Journal of Gastroenterology 44 (9): 879–888. doi:10.1007/s00535-009-0102-2. ISSN 1435-5922. PMID 19568687.  
  17. ^ Thomas, Mc (February 2000). "Diuretics, ACE inhibitors and NSAIDs--the triple whammy". The Medical journal of Australia 172 (4): 184–5. ISSN 0025-729X. PMID 10772593.  
  18. ^ De, Broe, Me; Elseviers, Mm (February 1998). "Analgesic nephropathy". New England Journal of Medicine 338 (7): 446–52. doi:10.1056/NEJM199802123380707. ISSN 0028-4793. PMID 9459649.  
  19. ^ Moore, De (2002). "Drug-induced cutaneous photosensitivity: incidence, mechanism, prevention and management". Drug safety : an international journal of medical toxicology and drug experience 25 (5): 345–72. doi:10.2165/00002018-200225050-00004. ISSN 0114-5916. PMID 12020173.  
  20. ^ Østensen, Me; Skomsvoll, Jf (March 2004). "Anti-inflammatory pharmacotherapy during pregnancy". Expert opinion on pharmacotherapy 5 (3): 571–80. doi:10.1517/14656566.5.3.571. ISSN 1465-6566. PMID 15013926.  
  21. ^ Cervera, R; Balasch, J (2004). "The management of pregnant patients with antiphospholipid syndrome". Lupus 13 (9): 683–7. doi:10.1191/0961203304lu1092oa. ISSN 0961-2033. PMID 15485103.  
  22. ^ Graham, Gg; Scott, Kf; Day, Ro (2005). "Tolerability of paracetamol". Drug safety : an international journal of medical toxicology and drug experience 28 (3): 227–40. doi:10.2165/00002018-200528030-00004. ISSN 0114-5916. PMID 15733027.  
  23. ^ Wilkes, Jm; Clark, Le; Herrera, Jl (November 2005). "Acetaminophen overdose in pregnancy". Southern medical journal 98 (11): 1118–22. doi:10.1097/01.smj.0000184792.15407.51. ISSN 0038-4348. PMID 16351032.  
  24. ^ Dreillard, Audrey (2009-03-02). "Grossesse - Mamans attention" (in French). France Soir. http://www.francesoir.fr/societe/2009/03/02/grossesse-mamans-attention.html. Retrieved 2009-06-01.  
  25. ^ Allergy Capital: Adverse and allergic reactions to aspirin and NSAIDS. Accessed 2009.03.23.
  26. ^ Bombardier, C; Laine, L; Reicin, A; Shapiro, D; Burgos-Vargas, R; Davis, B; Day, R; Ferraz, Mb; Hawkey, Cj; Hochberg, Mc; Kvien, Tk; Schnitzer, Tj; Vigor, Study, Group (November 2000). "Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis". New England Journal of Medicine 343 (21): 1520–8, 2 p following 1528. doi:10.1056/NEJM200011233432103. ISSN 0028-4793. PMID 11087881.  
  27. ^ Chandrasekharan, Nv; Dai, H; Roos, Kl; Evanson, Nk; Tomsik, J; Elton, Ts; Simmons, Dl (October 2002). "COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression" (Free full text). Proceedings of the National Academy of Sciences of the United States of America 99 (21): 13926–31. doi:10.1073/pnas.162468699. ISSN 0027-8424. PMID 12242329. PMC 129799. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=12242329.  
  28. ^ Kis, B; Snipes, Ja; Busija, Dw (October 2005). "Acetaminophen and the cyclooxygenase-3 puzzle: sorting out facts, fictions, and uncertainties" (Free full text). The Journal of pharmacology and experimental therapeutics 315 (1): 1–7. doi:10.1124/jpet.105.085431. ISSN 0022-3565. PMID 15879007. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15879007.  

External links


Simple English

Non-steroidal anti-inflammatory drugs (often shortened to NSAIDs) are drugs that have analgesic or fever-reducing properties, but that are not based on steroids. Higher doses of such drugs can also be used to fight inflammation. Such drugs are special in that usually they are not narcotic, that is they do not induce sleep. Well-known examples of such drugs are aspirin, diclofenac and ibuprofen.



Citable sentences

Up to date as of December 17, 2010

Here are sentences from other pages on Non-steroidal anti-inflammatory drug, which are similar to those in the above article.








Got something to say? Make a comment.
Your name
Your email address
Message