NONSTEROIDAL ANTI-INFLAMMATORY DRUGS, ACETAMINOPHEN, & DRUGS USED IN GOUT A 55-year-old man takes aspirin 500 mg for headache.

1. The effects of aspirin do not include (A) Reduction of fever (B) Reduction of prostaglandin synthesis in inflamed tissues (C) Impaired autoregulation of kidney function (D) Reduction of bleeding tendency (E) Tinnitus and vertigo Answer 1. Aspirin clearly increases bleeding tendency (by its antiplatelet effects). The answer is (D). 2. Which one of the following pairs of a drug effect and mechanism of action is false? (A) Allopurinol action in gout: Inhibits oxidation of hypoxanthine (B) Aspirin antiplatelet action: Inhibits cyclooxygenase (C) Hydroxychloroquine antirheumatic action: Interferes with T Iymphocyte action (D) Probenecid uricosuric action: Increases secretion of uric acid by the loop of Henle (E) Indomethacin closure of patent ductus arteriosus: Blocks PGE production in the ductus of the newborn Answer 2. Probenecid inhibits the reabsorption of uric acid in the proximal tubule. (Both secretion and reabsorption of weak acids occur in the proximal tubule, not the loop of Henle.) The answer is (D). 3. Which one of the following effects does not occur in salicylate intoxication? (A) Hyperventilation (B) Hypothermia (C) Metabolic acidosis (D) Respiratory alkalosis (E) Tinnitus Answer 3. Salicylate intoxication is associated with hyperthermia, not hypotherrnia, because the drug causes uncoupling of oxidative phosphorylation, resulting in increased metabolism. The answer is (B). 4. Which one of the following drugs is not useful in dysmenorrhea? (A) Aspirin (B) Colchicine (C) Ibuprofen (D) Rofecoxib (E) Naproxen Answer 4. Primary dysmenorrhea is caused by excessive production of prostaglandin F2a. NSAIDs

that inhibit cyclooxygenase are far more effective in relieving symptoms than other analgesics. Colchicine, which is not analgesic and is anti-inflammatory only in gout and Mediterranean fever, would never be used in this condition. The answer is (B). 5. Which of the following drugs is MOST likely to increase serum concentrations of conventional doses of methotrexate, a weak acid that is primarily cleared in the urine? (A) Acetaminophen (B) Allopurinol (C) Colchicine (D) Hydroxychloroquine (E) Probenecid Answer 5. Methotrexate, a weak acid, depends upon active tubular excretion in the proximal tubule for efficient elimination. Probenecid competes with methotrexate for binding to the proximal tubule transporter and thereby decreases the rate of clearance of methotrexate. The answer is (E). 6. The main advantage of ketorolac over aspirin is that ketorolac (A) Can be combined more safely with an opioid such as codeine (B) Can be obtained as an over-the-counter agent (C) Does not prolong the bleeding time (D) Is available in a parenteral formulation that can be injected intrarnuscularly or intravenously (E) Is less likely to cause acute renal failure in patients with some preexisting degree of renal impairment Answer 6. Ketorolac exerts typical NSAill effects. It prolongs the bleeding time and can impair renal function, especially in a patient with preexisting renal disease. Ketorolac is not available overthe-counter. Its primary use is as a parenteral agent for pain management, especially for treat- ment of postoperative patients. The answer is (D). A 52-year-old woman presented with intense pain, warmth, and redness in the first toe on her left foot. Examination of fluid withdrawn from the inflamed joint revealed crystals of uric acid. 7. In the treatment of this woman's acute attack of gout, the advantage of using indomethacin instead of colchicine is that indomethacin is (A) Less likely to cause acute renal failure (B) Less likely to cause severe diarrhea (C) Less likely to precipitate sudden gastrointestinal bleeding (D) More likely to prevent another acute attack (E) More likely to reduce the symptoms of inflammation Answer 7. Indomethacin and colchicine have equivalent efficacy in the treatment of acute gout. Colchicine is now more likely to be used chronically to prevent other attacks. Indomethacin is more-not less-likely to precipitate sudden gastrointestinal bleeding and acute renal failure. In the dose used to treat acute gout, colchicine frequently causes significant diarrhea. The answer is (B). 8. Over the next 7 months, the patient had two more attacks of acute gout. Her serum concentration of uric acid was elevated. The decision was made to put her on chronic drug therapy to try to prevent subsequent attacks. Which of the following drugs could be used to decrease this woman's

rate of production of uric acid? (A) Allopurinol (B) Aspirin (C) Colchicine (D) Hydroxychloroquine (E) Probenecid Answer 8. Allopurinol is the only drug listed that decreases production of uric acid. Probenecid increases uric acid excretion. Colchicine and hydroxychloroquine do not affect uric acid metabolism. Aspirin actually slows renal secretion of uric acid and raises uric acid blood levels. It should not be used in gout. The answer is (A). 9. A 54-year-old woman presented with signs and symptoms consistent with an early stage of rheumatoid arthritis. The decision was made to initiate NSAID therapy. Which of the following patient characteristics is a possible reason for the use of celecoxib in the treatment of her arthritis? (A) A history of a severe rash after treatment with a sulfonarnide antibiotic (B) A history of gout (C) A history of peptic ulcer disease (D) A history of sudden onset of bronchospasm after treatment with aspirin (E) A history of type 2 diabetes Answer 9. Celecoxib is a COX-2-selective inhibitor. Its advantage over nonselective NSAIDs may be re- duced gastrointestinal toxicity. Celecoxib is being used in patients who need NSAIDs but who also have a high risk of gastrointestinal toxicity, such as patients with a history of ulcer disease. Celecoxib is a sulfonamide, so it should be avoided in patients with sulfonamide allergy. Like all NSAIDs, it should not be used in patients with hypersensitivity to aspirin. It does not offer any advantages over other NSAlDs in patients with gout or diabetes. The answer is (C). 10. Although the patien s disease was adequately controlled with an NSAID and methotrexate for some time, her symptoms began to worsen and radiologic studies of her hands indicated progressive destruction in the joints of several fingers. Treatment with a new second-line agent for rheumatoid arthritis was considered. This drug is available only in a parenteral formulation; its mechanism of anti-inflammatory action is antagonism of tumor necrosis factor. The drug being considered is (A) Cyclosporine (B) Etanercept (C) Penicillarnine (D) Phenylbutazone (E) Sulfasalazine Answer 10. Etanercept is a recombinant protein that binds to tumor necrosis factor and prevents its inflam- matory effects. The answer is (B). Skill keeper 1. Morphine is the prototype of the strong opioids. Meperidine is a variant used commonly for analgesia. Methadone is a strong agonist used in maintenance programs for patients addicted to

opioids. Codeine, oxycodone, and hydrocodone are moderate agonists, whereas propoxyphene is a weak agonist. 2. Constipation and sedation occur with therapeutic doses; constipation should be man- aged with stool softeners. In overdose, opioids cause a triad of pinpoint pupils, coma, and respiratory depression. 3. Naloxone, a nonselective opioid receptor antagonist, is the antidote for opioid overdose.