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77 Cards in this Set
- Front
- Back
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what is MOA of colchicine?
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binds tubulin and prevents polimerization
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what is the use of colchicine?
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preventative
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what are the MOA of nsiads in Gout?
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decrease WBC migration/phagocytism
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what is the MOA of probenicid
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decreases UA reabsorption in the kidney by competition
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what is the contraindication of probenicid?
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patients with kidney stones from gout.
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what is the MOA of allopurinal?
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decreases production of uric acid by blocking xanthine oxidase
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what are some important drug interactions of allopurinal?
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6mercaptopurine
azothioprine |
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what is the use of probenicid in gout?
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tophouse or long standing gout
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what is the use of allopurinal?
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chronic gout
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what is feboxostat?
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nonpurine version of allopurinaol
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what is MOA of pegloticase
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convertes UA to allountosin
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what are the ezyme based antigout drugs?
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pegloticase
RAsboricase |
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what is an adverse reaction with enzyme antigout drugs?
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hemolytic anemai
g6pd difiency anaphalaxis |
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what is pegloticase use for?
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chronic refractory gout
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when is rasboricase used?
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in cancer therapy to deal with tumor lysis syndrome
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what are the main treatment of acute gouty attack?
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NSAIDs
corticosteroids |
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what is the frontline treatment for chronic gout?
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allopurinol
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what is the pathology of gout?
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Hyperuricemia can be caused by either under-excretion of uric acid by the kidney or overproduction of uric acid.
b. Urate crystals deposited in a joint are phagocytosed by synoviocytes, which then secrete inflammatory mediators, which attract and activate PMNs and MNPs. |
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what is acute gouty arthritis?
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c. Acute gouty arthritis refers to an acute attack with pain, swelling, and redness of a joint.
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what is chronic tophaceous gout?
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d. Chronic tophaceous gout refers to chronic deposition of monosodium urate in subcutaneous tissue, joints, cartilage, and renal parenchyma. Nodular masses (tophi) are deposited throughout the body.
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how is uric acid handled by the kidney?
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b. Uric acid is freely filtered at the glomerulus. It also both reabsorbed and secreted in the middle segment (S2) of the proximal tubule. Reaborption is predominantly by the organic anion transporter family URAT-1. Net uric acid excreted is ~10% of what is filtered, meaning that most is reabsorbed.
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what transporter is reponsible for reabsorption of uric acid?
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organic anion transporter family URAT-1
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what are the extrea articular manifestations of hyperuricemia?
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i. Gouty nephropathy
ii. Obstructive nephropathy: acute intratubular crystal deposition leading to acute renal failure. iii. Nephrolithiasis: kidney stones |
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what are the causes of under excretion of uric acid?
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i. Drug induced hyperuricemia: diuretics (most common), aspirin (dual effect), ethambutal, L-dopa, cyclosporine, alcohol, nicotine
ii. Miscellaneous medical disorders: uncontrolled diabetes |
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what are the causes of overproduction of uric acid?
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i. Increased rate or purine synthesis due to an enzyme defect: decreased HGPRT or increased PRPP synthetase
ii. Increased rate of cellular turnover: myeloproliferative and lymphoproliferative disorders or cancer chemotherapy. |
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what is the MOA of colchicine?
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i. Mechanism: binds intracellular protein tubulin, preventing its polymerization into microtubules. This inhibits migration of leukocytes and phagocytosis, and inhibits the formation of leukotriene B4.
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what are the toxic effects of colchicine?
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abdominal discomfort, nausea, and diarrhea
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what is the main use of colchicine?
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acute gouty arthritis
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Is colchicine widely used for gout anymore?
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iv. Because of the toxic effects, treatment of gout is largely switching to NSAIDs.
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what are the NSAIDs usually used in gout?
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indomethacin
naproxen sulindac |
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what is the MOA NSAIDs for gout?
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i. Mechanism: inhibits PG synthesis, inhibits urate crystal phagocytosis
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what are the uricosuric agents?
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probenecid
sulfinpyrazone |
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what is the MOA of the uricosuric agents?
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a. Mechanism: inhibit uric acid reabsorption, decrease urate concentration, decrease body pool of urate in patients with tophaceous gout.
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what are the toxic effects of the uricosuric agents?
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GI irritation, hypersensitivity
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what is MOA of febuxostat?
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i. Mechanism: non-purine, potent, selective inhibitor of xanthine oxidase
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what is the use of febuxostat?
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well tolerated when there is allopurinol intolerance
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what are the side effects of febuxostat/
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diarrhea, nausea, vomiting, liver function.
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what are the adverse drug intereactions of febuxostat and allopurinal?
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a. 6-MP and azathioprine are partially metabolized by xanthine oxidase. Inhibition of xanthine oxidase by allopurinol and febuxostat decreases metabolism of 6-MP and azathioprine, increasing the chance of toxicity.
b. There may also be interactions with oral anticoagulants and an increased risk of ampicillin-induced rash. |
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how is hyperuriciemia defined?
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>7mg/dL in men
>6mg/dL in women |
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how is Uric acid eliminated from body?
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freely filtered at glomerulus
both reabsorption and sectretion in proximal tubule net uric acid excreted is 10% of that filtered. |
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what is the main transporter responsible for uric acid reabsorptino?
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URATE-1
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what are the drug causes of underexcretion of uric acid?
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diuretics,
aspirin ethamutal L-dopa cyclosporine alcohol nicotine |
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what is normal 24h secretion of UA?
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600mg
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what is the duel effect of aspririn on UA?
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low does preferentially inhibits UA secretion causing hyperuricemia
high doses such as those used in treatment of inflammation preferentially causes inhibition of UA reabsorption causes hypuricemia. |
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what enzyme deficinecy can cause gout?
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HGPRT defiency
HGPRT is responsible for purine salvalge pathway. |
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what are the causes of overproduction of uric acid?
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HGPRT deficicney accompanied by increased rate of purine synthesis de novo ie increased PRPP
increased rate of cell turnover; such as myeloproliferative and lyphoproliferative disorders and in cancer chemotherapy. |
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what is the MOA of colchicine?
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binds intracellaur protein tubulin prevents polymerazation into microtubules
inhibits migration of leukocytes and phagocytosis inhibits the formation of leukotriens B4 |
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what are the toxic effects of colchicine?
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abdominal discomfort
nausea and diarrhea |
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what is the main use of colchicine?
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acute gouty arthritis
can be used profalcatively |
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what is the MOA of indomethacin?
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inhibits PG synthetase, inhibits urate crystal phaogcytosis
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when is indomethacin used?
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in acute gouty attacks
prefered over colchicine because of the side effects colchicine has |
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what is prefered for treatement of acute gouty arithritis?
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NSAIDs are prefered over colchacine due to GI side effects of colchacine
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what is MOA of naproxn?
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inhibits migration of leukocytes inhibits urate cystral phagocytosis
useful in acute gouty attack NSAIDs |
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what are the NSAIDs used in gout?
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naproxyn, and indomethcin
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what is the main effects of the uricosuric agents?
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inhibits uric acid reabsorption
decreases serum urate concetration decreases pool of urate in pts with tophaccous gout maintains large urine volume |
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what is important consideration for uricosuric agents use in pt with urine issue?
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must be able to maintain high urine volume otherwise all the UA that is secreted into the tubules may cause obstuctions or stones. you need high flow to keep the tubules clear.
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how is uricosuric agents dosed?
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start low and slowly increase
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when is uricosuric agents used?
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pt can pee freely
pt has no kidney stones mainly used in tophous chronic gout not acute gouty attack. |
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what are the uricosuric agents?
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probenecid
sulfinpyrazone |
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what are the toxic effect of probenecid?
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GI irritation
hypersensitivity:mild skin rash |
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how is probenecid dosed?
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250mg twice daily for 1wk, 500mg twice daily increased gradually to a max dose of 2g
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what is difference btw sulfinpyrazone and probenecid?
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sulfinpyrazone lacks antiinflammortay and analgesic effects
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what is the doseing for sulfinpyrzone?
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start100-200mg twice a day incresae to maintainence dose of 200-800mg/d
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what are the 2 MOA of allopurinol?
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inhibition of xanthine oxidase
decresaes intracellular concentration of PRPP also its metobolite oxypurinol inhibits xanthine oxidase |
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what is toxicity of allopurinol?
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allergic skin reactions
GI intolerance |
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what is the half life of allopurinol?
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2-3hours but its metabolite has half life of 18-30hours
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how is allopurinol dosed?
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300mg once daily
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what are the drug intereactions of allopurinol?
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6-MP and azathioprine(are both inactivated by xanthine oxidase)
oral anticoagulants(inhibit metabolism) |
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what is febuxostat?
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nonpurine inhibitor of xanthine oxidase
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what are the side effects of fubuxostat?
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diarrhea, nausea, vomiting, liver function issues with increased transaminase
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what is febuxostat used for?
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chronic gout 40-80mg daily
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what are the drug interaction of febuxostat?
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6-MO and azathioprine
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what is pegloticase?
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peglyated uric acid specific enzyme not usually found in humans
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what is pegloticase used for?
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treatment of chronic gout in patients refractory to conventional therapy
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what is the dose of pegloticase?
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8mg IV infusion every two weeks
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what are teh adverse effects of pegloticase?
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anaphylaxis, gout flares, naursea
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what is rasburicase?
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recombinant uricase
only used single course in hyperuricemia due to turmo lysis adverse effects is hemolysis in pt with G6PD deficiency. |
