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Pain and inflammation sometimes occur in a circadian rhythm (daily rhythmic cycle based on a 24 hour interval). Therefore NSAIDs may be more effective at certain times.

NSAIDs are divided into two groups: those with plasma (blood) half-lives less than 6 hours (i.e. aspirin, diclofenac, ibuprofen) and those with half-lives greater than 10 hours (i.e. diflunisal, piroxicam, and sulindac). Since it takes three to five half-lives to stabilize blood levels, NSAIDs with longer half-lives require a loading dose to be given (large dose given initially). The "half-life" is the time it takes a drug to go down to half of its initial level.

Prostaglandins, which are inhibited by NSAIDs, function in the body to protect the stomach lining, promote clotting of the blood, regulate salt and fluid balance, and maintain blood flow to the kidneys when kidney function is reduced. By decreasing prostaglandins, NSAIDs can cause stomach irritation, bleeding, fluid retention, and decreased kidney function.

Synovial fluid (joint fluid) concentrations are 60% of plasma concentrations regardless of type of NSAID or its half-life. Synovial fluid is mostly the site of action of NSAIDs.

NSAIDs are 95% albumin (protein) bound. The unbound fraction of the NSAID is increased in patients with low albumin concentrations such as in active rheumatoid arthritis and the elderly.

Since NSAIDs bind to plasma proteins they may be displaced by or may displace other plasma-bound drugs such as coumadin, methotrexate, digoxin, cyclosporine, oral antidiabetic agents, and sulfa drugs. This interaction can enhance either therapeutic or toxic effects of either drug.

Due to their different chemical properties some NSAIDs have substantial biliary (bile ducts, gallbladder) excretion (i.e. indomethacin , sulindac) and others are metabolized pre-excretion, while a few are excreted in the urine unchanged.

NSAID studies which have shown a variation in patient response attribute a lower rate of adherence to one NSAID when other NSAIDs are known to be available. The response to and preference of an NSAID may relate to more than just symptom control.

About 60% of patients will respond to any single NSAID. A trial period of three weeks should be given for anti-inflammatory effectiveness to be observed. About 10% of rheumatoid arthritis patients will not respond to any NSAID.

A study in the United Kingdom revealed ibuprofen as the lowest risk for causing serious upper gastrointestinal distress. Naproxen, indomethacin, and diclofenac were viewed as an intermediate risk. Azapropazone, and piroxicam had the highest risk.

Antipyretic and anti-inflammatory effects of NSAIDs can mask the signs and symptoms of infection.

Adverse effects of NSAIDs which can occur at any time include renal (kidney) failure, hepatic (liver) dysfunction, bleeding, and gastric (stomach) ulceration.

NSAIDs (particularly indomethacin) can interfere with the pharmacologic control of hypertension and cardiac failure in patients who take beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, or diuretics.

Long-term use of NSAIDs may have a damaging effect on chondrocyte (cartilage) function. Commonly used NSAIDs include: Ansaid, Arthrotec, Aspirin, Cataflam, Clinoril, Daypro, Dolobid, Feldene, Ibuprofen, Indocin, Ketoprofen, Lodine, Meclomen, Mobic, Nalfon, Naproxen, Ponstel, Relafen, Tolectin, and Voltaren.