A 56-year-old man comes to the urgent care center with severe knee pain. He was feeling well until he awoke this morning with acute pain, redness, and swelling in the knee. The patient does not smoke but did drink heavily at a wedding reception the night before. Past medical history is notable for recent peptic ulcer disease. He is treated with oral colchicine and experiences significant relief of symptoms within 12 hours. The drug used in this patient most likely affects which of the steps shown in the diagram below?

Question

A 56-year-old man comes to the urgent care center with severe knee pain.  He was feeling well until he awoke this morning with acute pain, redness, and swelling in the knee.  The patient does not smoke but did drink heavily at a wedding reception the night before.  Past medical history is notable for recent peptic ulcer disease.  He is treated with oral colchicine and experiences significant relief of symptoms within 12 hours.  The drug used in this patient most likely affects which of the steps shown in the diagram below?

Quizplus · Accepted Answer

This patient with acute atraumatic monoarticular arthritis involving the knee has typical symptoms of gout. The usual first-line treatment of acute gouty arthritis is nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, indomethacin), but these are relatively contraindicated in patients with a history of peptic ulcer. Colchicine can also be used to treat acute gouty arthritis and results in resolution of symptoms in most patients. Colchicine works primarily by inhibiting microtubular polymerization. It binds to the tubulin protein that helps form microtubules, preventing their aggregation. This in turn disrupts cytoskeletal-dependent functions such as chemotaxis, phagocytosis, and degranulation. Colchicine also reduces the formation of leukotriene B₄. It does not have any effect on the metabolism or urinary excretion of uric acid. Important adverse effects of colchicine are nausea, abdominal pain, and diarrhea. Colchicine should not be used in elderly patients or those with severe renal dysfunction. (Choices A and E) Glucocorticoids inhibit the enzyme phospholipase A₂, which converts membrane phospholipids to arachidonic acid. This in turn decreases the formation of inflammatory prostaglandins and leukotrienes. Glucocorticoids can be given systemically or by intra-articular injection for treatment of gout in patients who cannot take NSAIDs or colchicine. (Choices B and D) The leukotriene pathways can be blocked by inhibiting the 5-lipoxygenase pathway or by blocking the leukotriene receptors. Zileuton is a specific inhibitor of the enzyme 5-lipoxygenase and inhibits leukotriene formation (LTB₄, LTC₄, LTD₄, and LTE₄). Montelukast inhibits LTD₄ receptors. Leukotriene modifiers are used in the treatment of asthma and allergic rhinitis but have no role in the treatment of gout. (Choice C) Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to prostanoids. It exists in 2 isoforms, COX-1 and COX-2. COX-2 is an inducible enzyme that is upregulated in inflammatory cells to increase synthesis of pro-inflammatory arachidonic acid metabolites. Standard NSAIDs (eg, indomethacin, ibuprofen) inhibit both COX-1 and COX-2, while selective COX-2 inhibitors (eg, celecoxib) inhibit only COX-2. Educational objective: Colchicine is used for treatment of acute gouty arthritis in patients who cannot take nonsteroidal anti-inflammatory drugs. It inhibits leukocyte migration and phagocytosis by blocking tubulin polymerization. Significant side effects of colchicine include nausea and diarrhea. __________ References: Mechanism of action of colchicine in the treatment of gout. (http://www.ncbi.nlm.nih.gov/pubmed/25151572)

A 56-Year-Old Man Comes to the Urgent Care Center with Severe