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Chapter: Modern Pharmacology with Clinical Applications: Opioid and Nonopioid Analgesics

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Arylpropionic Acid Derivatives

Ibuprofen (Advil), flurbiprofen (Ansaid), fenoprofen (Nalfon), ketoprofen (Orudis), and naproxen (Naprosyn) are all 2-substituted propionic acid derivatives.

Arylpropionic Acid Derivatives

Chemistry and Mechanism of Action

Ibuprofen (Advil), flurbiprofen (Ansaid), fenoprofen (Nalfon), ketoprofen (Orudis), and naproxen (Naprosyn) are all 2-substituted propionic acid derivatives. They block the production of prostaglandins via inhibition of COX and therefore are similar to the salicylates in thatthey produce analgesia, antipyresis, and antiinflamma-tory effects. However, they are more potent than aspirin, with a decreased incidence of side effects such as gastric irritation. Ketoprofen inhibits lipoxygenase and COX, thus decreasing the production of both leukotrienes and prostaglandins. It also decreases lysosomal release of en-zymes in inflammatory diseases. The principal differ-ences among these drugs lie in the time to onset and du-ration of action. Naproxen has a long half-life, whereas fenoprofen and ketoprofen have short half-lives. All of the drugs are extensively metabolized in the liver and re-quire adequate kidney function for clearance of the metabolites. The drugs vary in plasma protein binding, but clearly all are bound to a relatively high degree and can interfere with the binding of other drugs that com-pete for plasma protein binding (as described for as-pirin). The one exception is ketoprofen, which although highly bound to plasma proteins, does not appear to al-ter the binding of other drugs.

Clinical Uses, Adverse Effects, and Contraindications

The arylpropionic acid derivatives are useful for the treat-ment of rheumatoid arthritis and osteoarthritis, for re-duction of mild to moderate pain and fever, and for pain associated with dysmenorrhea. Side effects of the drugs are similar to but less severe than those described for the salicylates. Those who are sensitive to salicylates also may be sensitive to and have adverse reactions when taking ibuprofen and related drugs. Acute hyper-sensitivity to ibuprofen has been reported in patients with lupus. The hypersensitivity reaction to sulindac can be fatal. The use of sulindac has also been linked to cases of acute pancreatitis. The use of dimethylsulfoxide (DMSO) topically in combination with sulindac has been reported to induce severe neuropathies. The con-current use of ibuprofen with aspirin reduces the anti-inflammatory effects of both drugs. Ibuprofen is con-traindicated in patients with aspirin sensitivity leading to bronchiolar constriction and in patients with an-gioedema. As with all NSAIDs, renal and liver function should be normal for adequate clearance of the drugs.

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