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44 Cards in this Set

  • Front
  • Back
relation of gout with hyperuricemia
gout is always preceeded by hyperuricemia, but hyperuricemia does not always lead to gout
transient attacks of gout initiated by?
crystallization of urates in and around joints
podagra
gout of greater toe/ most common joint affected
tophi
lg aggregates of urate crystals and the surrounding inflammatory response
Lesch-Nyhan syndrome
x-linked recessive d/o affecting only males in which HGPRT(required for salvage pathway) is totally absent
four stages of gout
1. asymptomatic hyperuricemia
2. acute gouty arthritis
3. intercritical gout
4. chronic tophaceous gout
renal manifestations of gout
-HTN
-renal colic(uric acid nephrolithiasis in 10-25%
-chronic gouty nephropathy(20% die of renal failure)
MOA of allopurinol and febuxostat
block synthesis of uric acid and xanthine oxidase inhibitor
MOA of probenecid
increase uric acid excretion with a uricosuric agent
indications for pegloticase
chronic gout refractory to conventional therapy
colchicine
blocks entry of leukocytes into affected joints with microtubule disrupting agent--used to limit inflammation
tx of pain and inflammation of gout
-NSAIDs are effective @ inflammatory doses
-steroids can be given orally or by interarticular injection
ASA and gout
contraindicated since salicylate competitively inhibits the active tubular secretion of urate, causing net urate retention
Acid urine promotes urate crystallization, therefore tx by?
intaining an alkaline urine with liberal fluid intake and sodium bicarbonate; continue until serum uric acid normalizes and tophi disappear
MOA of uricosuric agents
block active reabsorption(normally 80% reabsorbed) and enhance urinary uric acid excretion
Probenecid (uricosuric agent)
MOA
-inhibits tubular reabsorption of urate, increases excretion and decreases serum levels
what is meant by probenecid causing "mobilization"
retards urate depostion and promotes reabsorption of urate deposits
Probenecid dosing
-initiate with small doses to avoid dumping large amts of urate into urine and possible stone formation
-maintain adequate hydration and alkalinize the urine
Probenecid is indicated for tx of gout in pts who have no hx of?
nephrolithiasis
DI of probenecid
-anionic form may competitively inhibit the active tubular secretion of other organic acids
-beneficial interaction with beta lactams
probenecid pt info
-avoid ASA
-may take with food or antacid for GI upset
-drink 6-8 full glasses per day to prevent ddevelopment of kidney stones
-must take continuouslyfor therapeutic effect
allopurinol
xanthine oxidase inhibitor--decrease production of uric acid without affecting synthesis of vital purines
oxipurinol
active metabolite of allopurinol
allopurinol warnings/ADR
--allergic skin rash/severe hypersensitivity rxn
--avoid in acute gout attacks due to mobilization/can give maintenance doses of colchicine prophylactically
-fluid intake >/=2L required to prevent acid urine
allopurinol pt info
-take with food or milk
-drink 10-12glasses of fluid q day
-avoid agents which acidify the urine
Febuxostat
selective nonpurine xanthine oxidase inhibitor
indication for febuxostat
chronic management of hyperuricemia in gout pts
Febuxostat
1. DI
2. ADR
1.DI with meds metabolized by XO
2. gout flares at beginning of tx, use prophylactic therapy of NSAIDs or colchicine
Pegloticase
recombinant polyethylene glycol(PEG)-modified mammalian uricase(urate oxidase)
-XO inhibitor
Pegloticase MOA
oxidation of uric acid to allantoin (water soluble purine metabolite)resulting in lower serum uric acid levels
Peloticase indications
chronic gout refractory to conventional therapy in adults
Pegloticase Boxed Warning
for infusion-related and anaphylactic rxns;
-premedicate with antihistamines and corticosteroids
-prophylactic NSAIDs or colchicine starting 1 wk prior to 1st infusion an dcontinue 6 mo to prevent gout flares
contraindication of Pegloticase
G6PD deficiency=> increases hemolysis and methemoglobinemia
Cochicine MOA
binds to tubulin preventing polymerization--inhibition of leukocyte migration, decreased phagocytosis and diminished inflammatory response to deposited crystals, and blocks cell division by binding to mitotic spindles
Colchicine FDA safety concerns
--cases of fatal toxicity at therapeutic doses with other meds
-substantiallly lower dose as effective , but fewer ADR
Colchicine warnings
-do not give P-glycoprotein(Pgp) inhibitors or strong 3A4 inhibitors to pts with renal or hepatic impairment who are on colchicine
Colchicine indications
used for relief of acute gout attacks and for regular prophylactic use between attacks
-often effective in aborting an attack if taken at first sign of discomfort
Colchicine ADR
severe GI effects: N/V/D and abdominal pain
-diarrhea most common and dose limiting effect
-can tx diarrhea with opiates
tx of osteoarthritis is _______
empiric and should be directed at symptom relief
acetominophen for tx of osteoarthritis
-effective/recommended as initial therapy at max adult doses
-max daily dose: <4g/d
NSAIDs in tx of osteoarthritis
-used if any inflammatory component is present or if pain relief from acetominophen is inadequate
Antidepressants in tx of fibromyalgia
-dual mechanism antidepressants block reuptake of both NE and 5HT
Antidepressants approved for use in fibromyalgia
-duloxetine(Cymbalta)
-milnacipran(Savella)
pregabalin(Lyrica) in tx of fibromyalgia
-anticonvulsant
-1st FDA approved drug for fibromyalgia