A 35-year-old man with a known history of peptic ulcer disease comes to the physician with sudden onset of pain, swelling, and redness at the base of his great toe. The patient was awakened in the middle of the night by the pain and was unable to go back to sleep. He has no history of trauma to the joint. Physical examination shows swelling, erythema, and exquisite tenderness involving the right first metatarsophalangeal joint. Fine-needle aspiration of the joint shows needle-shaped, negatively birefringent crystals. After making the diagnosis, the physician prescribes an appropriate medication. Shortly after starting the medication, the patient develops nausea, vomiting, and diarrhea. Which of the following is the most likely mechanism of action of the drug prescribed to this patient?

Question

A 35-year-old man with a known history of peptic ulcer disease comes to the physician with sudden onset of pain, swelling, and redness at the base of his great toe.  The patient was awakened in the middle of the night by the pain and was unable to go back to sleep.  He has no history of trauma to the joint.  Physical examination shows swelling, erythema, and exquisite tenderness involving the right first metatarsophalangeal joint.  Fine-needle aspiration of the joint shows needle-shaped, negatively birefringent crystals.  After making the diagnosis, the physician prescribes an appropriate medication.  Shortly after starting the medication, the patient develops nausea, vomiting, and diarrhea.  Which of the following is the most likely mechanism of action of the drug prescribed to this patient?

Quizplus · Accepted Answer

11ec160b_3c7d_c73b_9249_7559a020849b_MD0001_00 Acute onset of pain and swelling of the first metatarsophalangeal joint and joint aspiration showing needle-shaped, negatively birefringent crystals are diagnostic for acute gouty arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of treatment for most patients. However, colchicine is often used in patients with mild-to-moderate renal failure, peptic ulcer disease, or other contraindications to NSAIDs. Colchicine is an effective anti-inflammatory agent in acute gouty arthritis and acts by binding to the intracellular protein tubulin, preventing tubulin polymerization into microtubules. This leads to impaired leukocyte migration and phagocytosis, reducing the inflammation seen in gouty arthritis. Because colchicine also disrupts microtubule formation in gastrointestinal mucosal cells, many patients develop diarrhea and, less commonly, nausea, vomiting, and abdominal pain. (Choices A and E) Probenecid decreases proximal tubular uric acid reabsorption, and allopurinol inhibits xanthine oxidase (converts xanthine to uric acid). These medications are prescribed to lower serum uric acid levels in chronic gout. These agents are contraindicated in acute gouty arthritis as they can mobilize tissue stores of uric acid and precipitate or worsen acute attacks. (Choice B) NSAIDs induce their anti-inflammatory effects by inhibiting cyclooxygenase (COX)-1 and COX-2 isoenzymes, thus blocking prostaglandin synthesis. Because they can cause significant gastrointestinal irritation (eg, nausea, dyspepsia, bleeding), their use is contraindicated in patients with peptic ulcer disease. (Choice D) Glucocorticosteroids exert their anti-inflammatory effect by inhibiting phospholipase A₂ activity. These medications can be used in acute gout and are not associated with significant diarrhea. Educational objective: Colchicine is a second-line agent for treating acute gouty arthritis. It inhibits tubulin polymerization and microtubule formation in leukocytes, reducing neutrophil chemotaxis and emigration to sites inflamed by tissue deposition of monosodium urate crystals. Gastrointestinal mucosal function is also impaired by microtubule disruption, leading to diarrhea and, less commonly, nausea, vomiting, and abdominal pain. __________ References: Safety profile of anti-gout agents: an update. (http://www.ncbi.nlm.nih.gov/pubmed/24378930)

A 35-Year-Old Man with a Known History of Peptic Ulcer