Term
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Definition
| metabolic disease a/w recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage |
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Term
| gout is a/w deposits of what? |
|
Definition
| monosodium urate in joints and cartilage |
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Term
| gout is usually a/w high serum levels of what? |
|
Definition
| uric acid - the major end product of purine metabolism |
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Term
| what cell makes synovial fluid? |
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Definition
|
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Term
| what happens to urate crystals in the joint space? |
|
Definition
| phagocytosed by synoviocytes |
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Term
| when synoviocytes phagocytose urate crystals that stimulates them to do what? |
|
Definition
| secrete PGE --> amplifies the inflammatory response |
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Term
| how is the inflammatory response in the joints amplified in gout? |
|
Definition
1. synoviocytes secrete PGE after they phagocytose urate crystals
2. PMN leukocytes migrate to joint space
3. macrophages ingest urate crystals --> then release more inflammatory factors |
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Term
| how do anti-inflammatory agents work in the treatment of gout? |
|
Definition
1. relieve pain of acute gouty attack
2. prevent recurrent episodes |
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Term
| what drugs are used to relieve pain of acute gouty attack and prevent recurrent episodes? |
|
Definition
| NSAIDs and corticosteroids |
|
|
Term
| what anti-inflammatory drugs are used in the treatment of gout? |
|
Definition
| NSAIDs and corticosteroids |
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|
Term
| mechanism of action of indomethacin as treatment for gout? |
|
Definition
| inhibits PGE synthesis and urate crystal phagocytosis |
|
|
Term
| 3 NSAIDs used to treat gout? |
|
Definition
1. indomethacin
2. naproxen
3. etoricoxib |
|
|
Term
| what is a selective COX-2 inhibitor used in the treatment of gout? |
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Definition
|
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Term
| mechanism of action of corticosteroids in the treatment of gout? |
|
Definition
1. reduce the production of inflammatory mediators
2. inhibit COX and PLA2 --> inhibits production of arachadonic acid (precursor to PGE and leukotrienes) |
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|
Term
| administration of corticosteroids for treatment of gout? |
|
Definition
oral --> can lead to systemic side effects
poor local injection for single joint involvement --> less systemic side effects |
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|
Term
| 2 corticosteroids used for treatment of gout? |
|
Definition
1. prednisone
2. methylprednisolosone |
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Term
|
Definition
| an alkaloid isolated from autumn locus |
|
|
Term
| administration of colchicine? |
|
Definition
| readily absorbed orally; often used IV |
|
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Term
| how is colchicine effective in treating gout? |
|
Definition
| dramatically relieves pain and inflammation |
|
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Term
|
Definition
1. binds tubulin --> prevents polymerization into tubules
2. inhibits leukocyte migration and pro-inflammatory agents release (like PGE) |
|
|
Term
| why is colchicine now a 2nd line drug? |
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Definition
| it is very effective but diarrhea is a common side effect that limits use |
|
|
Term
| what side effect of colchicine limits its use? |
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Definition
|
|
Term
| colchicine is a substrate for what? |
|
Definition
| CYP3A4 and P-glycoprotein efflux transporter |
|
|
Term
| when can colchicine have fatal toxicities and why? |
|
Definition
when the patient is also taking clarithromycin or cyclosporine
they are also substrates or block the same transporters and the amount of colchicine can reach toxic levels |
|
|
Term
| mechanism of probenecid and sulfinpyrazone? |
|
Definition
| enhance uric acid excretion by inhibiting renal reabsorption |
|
|
Term
| what usually happens to excreted uric acid? |
|
Definition
| reabsorbed in the proximal tubule of the kidney |
|
|
Term
| what must be maintained with use of probenecid and sulfinpyrazone? |
|
Definition
|
|
Term
| patients taking probenecid and sulfinpyrazone are at increased risk for what? |
|
Definition
|
|
Term
| probenecid and sulfinpyrazone are contraindicated in who? |
|
Definition
| individuals with kidney stones |
|
|
Term
| will probenecid and sulfinpyrazone alter the course of a gouty attack? |
|
Definition
|
|
Term
| how long do probenecid and sulfinpyrazone take to be effective? |
|
Definition
|
|
Term
| 2 xanthine oxidase inhibitors? |
|
Definition
1. allopurinol
2. febuxostat |
|
|
Term
| mechanism of allopurinol and febuxostat? |
|
Definition
| lower serum uric acid by inhibiting xanthine oxidase enzyme |
|
|
Term
| xanthine oxidase inhibitors are effective how in the treatment of gout? |
|
Definition
| in preventing recurrence of acute gouty arthritis and treating urate nephrolithiases (uric acid kidney stones) |
|
|
Term
| how are xanthine oxidase inhibitors used in the treatment of gout? |
|
Definition
| not helpful short term --> used in long term therapy |
|
|
Term
| when are xanthine oxidase inhibitors used in the treatment of gout? |
|
Definition
1. patients with high urine uric acid levels
2. impaired kidney function
3. allergies to probenecid or sulfapyrazone (S containing) |
|
|
Term
| adverse effects of xanthine oxidase inhibitors? |
|
Definition
1. hypersensitivity reactions
2. liver enzyme abnormalities |
|
|
Term
| allopurinol can have significant drug interaction with what drug? |
|
Definition
| 6-mercaptopurine - immunomodulator used in treatment of IBD |
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|
Term
| 6-mercaptopurine is normally inactivated by what? |
|
Definition
|
|
Term
| what happens when allopurinol and 6-mercaptopurine are given together? |
|
Definition
| increased levels of 6-mercaptopurine can lead to very serious leukopenia |
|
|
Term
|
Definition
| its synthesized from xanthine by xanthine oxidase |
|
|
Term
| what must be done when give allopurinol with 6-mercaptopurine? |
|
Definition
| dose of 6-mercaptopurine has to reduced >50% |
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|
Term
Uncle Bob has recently found out that he has gout. He also as diabetes and has been told that his kidney function isn’t stellar. After initial treatment with indomethacin, he has been placed long-term on a drug that does not require fully functioning kidneys. This drug is most likely:
a. Uric acid
b. Allopurinol
c. Probenicid
d. Propranolol |
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Definition
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