Nonsteroidal anti-inflammatory drugs
As their name suggests, nonsteroidal anti-inflammatory drugs (NSAIDs), are typically used to combat inflammation. Their anti-inflammatory action equals that of aspirin. They also have anal-gesic and antipyretic effects. Unlike aspirin’s effects, the effects of NSAIDs on platelet aggregation are temporary.
There are two types of NSAIDs: selective and nonselective. The nonselective NSAIDs include diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, and sulindac. The only selective NSAID available on today’s market is celecoxib. (See Risks of using selective NSAIDs.)
All NSAIDs (nonselective and selective) are absorbed in the GI tract. They’re mostly metabolized in the liver and excreted primar-ily by the kidneys.
Two isoenzymes of cyclooxygenase, known as COX-1 and COX-2, convert arachidonic acid into prostaglandins. The nonselective
NSAIDs block both COX-1 and COX-2. Selective NSAIDs block only the COX-2 enzyme.
The prostaglandins produced by COX-1 maintain the stomach lin-ing, while those produced by COX-2 cause inflammation. That’s why the nonselective NSAIDs, which inhibit COX-1 along with COX-2, commonly cause GI adverse effects. Selective NSAIDs, however, alleviate pain and inflammation without causing signifi-cant GI adverse effects because they inhibit only COX-2.
· NSAIDs are used primarily to decrease inflammation. They’re sec-ondarily used to relieve pain, but are seldom prescribed to reduce fever. (See Using nonselective NSAIDs safely.)
· COX-2 inhibitors are primarily used to relieve pain and to de-crease inflammation. These drugs are particularly useful in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, pri-mary dysmenorrhea, and familial adenomatous polyposis.
The following conditions respond favorably to treatment with NSAIDs:
· ankylosing spondylitis (an inflammatory joint disease that first affects the spine)
· moderate to severe rheumatoid arthritis (an inflammatory dis-ease of peripheral joints)
· osteoarthritis (a degenerative joint disease) in the hip, shoulder, or other large joints
· osteoarthritis accompanied by inflammation
· acute gouty arthritis (urate deposits in the joints)
· dysmenorrhea (painful menstruation)
· migraine headaches
· bursitis and tendonitis
· mild to moderate pain.
A wide variety of drugs can interact with NSAIDs, especially with indomethacin, piroxicam, and sulindac. Because they’re highly protein-bound, NSAIDs are likely to interact with other protein-bound drugs. Such drugs as fluconazole, phenobarbital, rifampin, ritonavir, and salicylates affect absorption of NSAIDs, whereas NSAIDs affect the absorption of such drugs as oral anticoagulants, aminoglycosides, ACE inhibitors, beta-adrenergic blockers, digox-in, dilantin, and many others. (See Adverse reactions to nonselec-tive NSAIDs and Adverse reactions to COX-2 inhibitors.)
Because NSAIDs are metabolized by the liver, drug-drug inter-actions have been identified for all of them. For example, these drugs decrease the clearance of lithium, which can result in lithi-um toxicity. They also reduce the antihypertensive effects of ACE inhibitors and diuretics.