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45 Cards in this Set
- Front
- Back
What causes gout?
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inbalance between uric acid production and renal excretion, producing hyperuricemia
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Where does uric acid usually come from?
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breakdown product of nucleic acids
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What are some symptoms of gout?
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1. acute inflammatory arthritis
2. fever 3. tophi-usually at big toe 4. kidney stones |
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What causes the acute inflammatory arthritis seen in gout?
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deposition of crystals of monosodium urate in and around joints and tendons
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How do gout attacks progress?
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short duration periodically at first, but if left untreated, become more frequent and last longer periods
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What is a tophi?
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large deposit of uric acid
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What is the pathophysiology of gout?
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synoviocytes phagocytize urate crystals->secrete IL-1 and PG->attract neutrophils and macrophages->neuts secrete LTB4 and PG; macros secrete PG and IL-1
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Who is primarily affected by gout?
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mid-life males (drinking wine and eating steaks)
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What are 3 pharmacologic treatments for gout?
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1. inhibit uric acid synthesis
2. increase uric acid elimination 3. inhibit immune responses to uric acid |
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What is the MOA of colchicine?
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binds to intracellular protein tubulin, preventing polymerization into microtubules->this prevents leukocyte migration and phagocytosis
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What drugs inhibit metabolism of colchicine?
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cimetidine and erythromycin
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What is an adverse effect of colchicine?
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narrow TI; can cause GI problems and hair loss
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Symptoms of acute oral overdose of colchicine?
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burning throat, bloody diarrhea, renal shutdown
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Chronic toxicity of colchicine includes:
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agranulocytosis and aplastic anemia; teratogenesis
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What is the first line drug for treatment of acute gouty arthritis? What is the first line drug for prevention of acute gouty arthritis?
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1. NSAIDs
2. colchicine |
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What is the main difference in NSAIDS vs. cochicine in gouty treatment?
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NSAIDS work faster by inhibiting PG synthesis
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Why can't NSAIDS be used as a prophylactic against gout?
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chronic adverse effects
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What are the 3 A's of NSAIDs?
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antipyretic, antiinflammatory, analgesic
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What NSAID is traditionally used to treat acute gouty arthritis? What are some problems with its use?
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indomethacin; GI and CNS effects
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Aside from indomethacin, what other NSAIDs can be used to treat gout?
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phenylbutazone and ibuprofen
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Although not normally used due to toxicities, what drugs can be used in resistant acute cases of gout?
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adrenal corticosteroids
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What are 2 inhibitors of uric acid synthesis?
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allopurinol and febuxostat (investigational)
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What is the MOA of allopurinol?
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competitively inhibits xanthine oxidase
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How are hypoxanthine and uric acid related?
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hypoxanthine comes from purine metabolism; it is converted to xanthine, then to uric acid
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What enzyme converts hypoxanthine to xanthine and xanthine to uric acid?
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xanthine oxidase
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In addition to competitively inhibiting xanthine oxidase, what other effect does allopurinol have on xanthine oxidase?
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after it binds to xanthine oxidase, it forms alloxanthine, which in turn inhibits xanthine oxidase
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How is allopurinol removed from the body? Long or short half-life?
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kidneys; long
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What effect does allopurinol have on 6 mercaptopurine and azathioprine (immunosuppressants)?
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inhibits their metabolism by xanthine oxidase
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What is the main side effect of allopurinol?
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allergic reactions (2%) like exfoliative dermatitis
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T or F: allopurinol can actually produce acute gouty arthritis
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true; give colchicine or NSAID first
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What is the therapeutic use of allopurinol?
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chronic treatment of gout (protects kidneys, prevents kidney stones, and eliminates tophi)
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How can allopurinol be used as a prophylactic?
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protect kidneys against uric acid precipitation and stone formation in patients with leukemia
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How do uricosuric drugs work? Should these be given in low or high doses?
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act at anionic transport sites in renal tubules to cause a net decrease in uric acid reabsorption; high doses
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What is the main risk in uricosuric drugs?
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formation of uric acid crystals in urine and deposition of UA in renal tissue
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What is a complication of uricosuric drugs? What should be given prior to this?
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until therapeutic dose is reached, they may cause acute attacks of gout; NSAIDs and colchicine
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What are the uricosuric drugs?
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probenecid (more common) and sulfinpyrazone
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What drug should NOT be used to treat gout if the patient’s daily urinary output of uric acid is greater than 600 mg/24 hours or if renal function is significantly compromised?
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probenecid
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What are some possible adverse effects of probenecid?
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allergic reaction, nephritic syndrome, and aplastic anemia,
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Therapeutic uses for probenecid?
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1. after acute gouty attacks
2. when allopurinol is not tolerated 3. when tophi appear |
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Probenecid should not be used to manage hyperuricemia associated with what?
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cancer chemotherapy
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What drugs can inhibit probenecid effects by interfering with active secretion of uric acid?
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salicylates
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What is a common adverse effect of Sulfinpyrazone?
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greater GI irritation than probenecid
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Why would you choose sulfinpyrazone over probenecid?
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less allergic reactions
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What is the general treatment algorithm for acute gouty attacks?
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NSAIDs 1st; colchicine 2nd
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What is the general treatment algorithm for chronic gout?
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allopurinol first; uricosurics second
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