A 48-year-old man comes to the office due to several hours of severe right knee pain. The patient has a history of peptic ulcer disease and gastroesophageal reflux disease. His right knee is swollen, erythematous, and tender. Arthrocentesis is performed and synovial fluid analysis shows needle-shaped, negatively birefringent crystals with many neutrophils. The medication given to this patient selectively binds to an interleukin-1 inducible enzyme that is highly expressed by inflammatory cells and undetectable in the surrounding normal tissue. Which of the following is most likely the drug used in this patient's treatment?

Question

A 48-year-old man comes to the office due to several hours of severe right knee pain.  The patient has a history of peptic ulcer disease and gastroesophageal reflux disease.  His right knee is swollen, erythematous, and tender.  Arthrocentesis is performed and synovial fluid analysis shows needle-shaped, negatively birefringent crystals with many neutrophils.  The medication given to this patient selectively binds to an interleukin-1 inducible enzyme that is highly expressed by inflammatory cells and undetectable in the surrounding normal tissue.  Which of the following is most likely the drug used in this patient's treatment?

Quizplus · Accepted Answer

11ec160b_3c7e_ffbd_9249_1d3d47fdc1c0_MD0001_00 Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyzes the conversion of arachidonic acid into prostanoids. It exists in 2 isoforms designated COX-1 and COX-2. COX-1 is constitutively expressed in various tissues and is involved in a number of "housekeeping functions" (eg, platelet aggregation, gastric mucosal protection, vascular homeostasis). COX-2 is an inducible enzyme that is undetectable in most tissues under normal conditions. During inflammation, infiltrating cells secrete cytokines (eg, interleukin-1, TNF-α) that cause COX-2 upregulation in the inflamed tissue. COX-2 then drives the synthesis of pro-inflammatory arachidonic acid metabolites. This patient's acute gout attack should be treated with an agent that provides prompt pain relief without exacerbating his gastrointestinal problems. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin, and naproxen inhibit both COX-1 and COX-2 and can cause significant gastrointestinal injury. Selective COX-2 inhibitors (eg, celecoxib) decrease inflammation but have no effect on COX-1, minimizing gastroduodenal toxicity. (Choice A) Like other NSAIDs, aspirin nonselectively inhibits both COX-1 and COX-2. Aspirin irreversibly modifies these enzymes; therefore, restoration of enzymatic activity requires synthesis of new enzymes. (Choice C) Colchicine binds to tubulin, which inhibits microtubule formation. This results in impaired neutrophil mitosis and decreased neutrophil chemotaxis. (Choice D) Infliximab is a monoclonal antibody that irreversibly binds to and inhibits TNF-α, a cytokine involved in the inflammatory response. TNF-α is an intercellular signaling protein, not an enzyme. (Choice E) Glucocorticoids (eg, prednisone) bind to cytoplasmic receptors that then translocate to the nucleus where the expression of anti-inflammatory peptides is upregulated. Glucocorticoids decrease COX-2 transcription but do not bind to COX-2 directly. Educational objective: Cyclooxygenase-2 (COX-2) is an inducible enzyme upregulated during inflammation by interleukin-1 and TNF-α. Selective COX-2 inhibitors (eg, celecoxib) decrease inflammation by inhibiting COX-2 production of pro-inflammatory arachidonic acid metabolites. Because they do not affect COX-1, they have minimal gastroduodenal toxicity. __________ References: Prostaglandins and inflammation. (http://www.ncbi.nlm.nih.gov/pubmed/21508345)

A 48-Year-Old Man Comes to the Office Due to Several