● Hematologic: Altered hemostasis through effects on platelet function. Pregnancy and lactation NSAIDs should be avoided during the first trimester and just before delivery; they may be used cautiously at other times
● Other: Skin eruption, sensitivity reactions, tinnitus, and hearing loss.
during pregnancy. NSAIDs appear in breast milk and should be used cautiously by breastfeeding mothers.
NSAID Classification ● Selective COX-2 inhibitors ○ Celecoxib ● Nonselective COX inhibitors ○ Acetic acid ▪ Diclofenac. ▪ Etodolac. ▪ Indomethacin.
▪ Oxaprozin.
○ Fenamate
▪ Meclofenamate. ▪ Meclofenamic acid.
○ Salicylate ▪ Aspirin.
▪ Diflunisal. ○ Naphthylalkanone ▪ Nabumetone. ○ Choline magnesium trisalicylate ▪ Salsalate. ○ Oxicam
▪ Sulindac. ▪ Tolmetin. ○ Propionic acid ▪ Fenoprofen. ▪ Flurbiprofen. ▪ Ibuprofen. ▪ Ketoprofen. ▪ Naproxen.
▪ Piroxicam. ▪ Meloxicam.
Nonselective COX inhibitors Approximately 17 million Americans take nonsteroidal anti- inflammatory drugs (NSAIDs) daily for treatment of pain or inflammation. These drugs are nonselective inhibitors of the enzymes cyclooxygenase (COX) 1 and 2, which convert arachidonic acid to prostaglandins. Unfortunately, they are also associated with serious adverse gastrointestinal effects, such as gastritis, dyspepsia, gastroduodenal ulcers, perforations, and bleeding. Endoscopic studies have shown that within one week of starting NSAID therapy, more than 30 percent of patients will have gastric erosions or ulcers, and within one year, approximately 3 percent will have significant gastrointestinal bleeding. As many as 15,000 deaths each year have been attributed to NSAID use in the United States. 2 Acetic acid NSAIDs ● Diclofenac ( Cataflam, Voltarren) : Relatively nonselective as a COX inhibitor, adverse effects occur in about 20 percent of users, include symptoms of gastrointestinal distress, bleeding, and ulceration. Used post-surgically in certain operations. ● Etodolac (Lodine) : Somewhat more COX-2 selective than most NSAIDs may cause less gastric toxicity in relation to ulcer disease that other nonselective NSAIDs. ● Indomethacin (Indocin) : A powerful nonselective COX inhibitor that may also decrease T-cell proliferations. Useful for rheumatic conditions and can reduce gingival inflammation in an oral rinse administration. At higher dosages, one-third of users have reactions requiring discontinuing the drug. Side effects include abdominal pain, diarrhea, gastrointestinal hemorrhage, and pancreatitis. Headache is experienced in up to one-quarter of users and is associated with dizziness, confusion, and depression. May interact with other medications. Should not be used in individuals with nasal polyps or angioedema, as it may precipitate an asthma attack. Propionic acid NSAIDs ● Fenoprofen (Nalfon): Most associated with rare toxicity of interstitial nephritis among all the NSAIDs. Other side effects include nausea, dyspepsia, peripheral edema, rash, central nervous system and cardiovascular effects, and tinnitus. Drug interactions. ● Flurbiprofen (Ansaid): Extensive hepatic metabolism; comparable in strength to aspirin in studies with rheumatoid arthritis and osteoarthritis; available in a topical form; effective after surgery; side effects similar to other NSAIDS, with slightly more pronounced adverse effects including ataxia or tremors.
● Ibuprofen (Motrin, Advil): Oral ibuprofen is often prescribed in low doses, at which it has analgesic, but not anti- inflammatory effects. Topical cream and liquid gel forms may be more effective for absorption into fascia and muscle. Gastrointestinal irritation and bleeding occur less frequently than with aspirin. Use of aspirin and ibuprofen together may decrease overall anti-inflammatory effects. Therefore, treatment with ibuprofen in individuals with increased cardiovascular risks may limit the heart protecting effects of aspirin. Contraindicated in individuals with nasal polyps, angioedema, and bronchospastic reactivity to aspirin. Has also been associated with rash, pruritus, tinnitus, dizziness, headache, and fluid retention. Renal difficulties occur (as with all NSAIDs) but very rarely. ● Ketoprofen (Orudis): Ketoprofen nonselectively inhibits COX and lipoxygenase, but is similar to the other NSAIDs in its effectiveness for the treatment of rheumatoid arthritis and osteoarthritis. Adversely affects the gastrointestinal tract and central nervous system. ● Naproxen (Nasprosyn, Aleve): Naproxen availability is 41 percent higher in women than in men and is effective for rheumatologic conditions in a slow release formula, topical preparation and as an eye-wash. Over the counter use of naproxen is associated with two times greater incidence of gastrointestinal bleeding than that of over-the-counter use of ibuprofen. Beyond normal NSAID-associated effects, rare cases of allergic pneumonitis, leukocytoclastic vasculitis and pseudopophyria are associated with use. ● Oxaprozin (Daypro): The major difference between this drug and other NSAIDs like it is its very long half-life, permitting dosage in a once-a-day formulation. Fenamate NSAIDs Meclofenamate sodium, mefenamic acid ( Ponstel) inhibit both COX and phospholipase A2. Meclofenamate has similar side effects to other NSAIDS, with slightly higher incidence of abdominal pain and diarrhea. It also enhances the effect of oral anticoagulants and is contraindicated in pregnancy. Mefanamic acid is less effective than aspirin as an anti-inflammatory, but is considerably more toxic. It should not be used for a period over one week. Naphthylalkanone NSAIDs Nabumetone (Relafen) : Nabumetone is the only nonacid NSAID currently available. Its half-life is greater than 24 hours, permitting a once-daily dose. It may be slightly less damaging to the stomach than other NSAIDs, but is more expensive,
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