Drugs Used in Gout Flashcards
metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage
gout
systemic disease caused by buildup of uric acid in joints, cause inflammation, swelling, and pain
gout
urate level >8mg/dL and 7mg/dL in women
hyperuricemia
most common first symptom of gout
pain in one joint of the lower extremity
end product of purine metabolism
uric acid
rate limiting step in the formation of uric acid
xanthine oxidase
serves no known biological functions, but body has content of 1.0-0.2 g
uric acid
T/F: Approximately 70-80% of uric acid is excreted via the kidneys
True
Types of gout
Primary and Secondary
result of innate defect in purine metabolism of uric acid excretion
primary gout
uric acid overproduction, impaired renal clearance of uric acid (underexcreters) or a combi of both are associated with
primary gout
hematologic disorders, drug-induced salicylates, diuretics (thiazide), ethambutol, pyrazinamide, nicotinic acid, ethanol, niacin and cyclosporine
secondary gout
tx goals for gout
- relieve pain and inflammation
- reduce serum uric acid conc (urate lithiasis)
- prevent recurrent gout attacks
drugs for acute gouty arthritis attack
- colchicine
- NSAIDs
- corticosteroids
antimitotic drug that is highly effective in relieving acute gout attack with a low-benefit to toxicity ratio
colchicine
T/F: Colchicine is used more often than NSAIDs due to its low-benefit to toxicity ratio
False: used less often
cause dose-dependent GI adverse effect (nausea, vomitin, bloating, emesis and diarrhea) that occur in up to 80% of px
oral colchicine
can be taken with or w/o food and sometimes used in combination with NSAIDs
colchicine
alkaloid isolated from autumn crocus (Colchicum autumnale)
colchicine
Colchicine relieves pain and inflammation of ___________________________________ w/o altering urate metabolism or excretion and w/o other analgesic effects
gouty arthritis in 12-24 hrs
NSAIDs are the _________________________ because of their excellent efficacy and minimal toxicity with short-term use
mainstay of therapy
most common adrs of NSAIDs involve ___________________ (gastritis, bleeding and perforation)
GI system
most extensively studied NSAID in the tx of acute gouty arthritis attack
indomethacin
Aside from inhibiting PG synthase, NSAIDs also inhibit _______________________ and reduce inflammation and pain in acute gout flare
urate crystal phagocytosis
Aspirin is not used in gout because it causes _________________________ at lower doses (less than or equal to 2.6 g/d)
renal retention of uric acid
All NSAIDs except ______________________________ have been successfully used to treat acute gouty episodes
aspirin, salicylates, and tolmetin
lowers serum uric acid and is theoretically a good choice
oxaprozin
T/F: All NSAIDs appear to be as effective and safe as older drugs like indomethacin
True
equivalents to NSAIDs for tx of acute gout flares
corticosteroids
Corticosteroids are effective when given ______________________________
intra-articularly, IV, or orally
oral corticosteroid
prednisone
long-acting corticosteroid administered through IM, intra-articular (if px is unable to take oral meds)
triamcinolone acetonide or methylprednisolone
corticosteroids ___________________ (increase/decrease) activation, proliferation, and survival of various inflammatory cells
decrease
corticosteroids also decrease the migration of neutrophils and inhibit __________________________ such as IL-1B
prostaglandins and proinflammatory cytokines
indicated as good alternative for px in whom NSAIDs or colchicine are contraindicated and in those w/renal impairment or CKD
corticosteroids
Corticosteroids are sometimes used in the tx of ______________________ by oral, intra-articular, systemic, or SC routes
severe symptomatic gout
goal is to achieve and maintain serum uric acid conc of less than 6mg/dL and preferable <5mg/dL
urate lowering therapy
reduction of serum urate conc can be accomplished by
- decreasing uric acid synthesis
- increasing renal excretion of uric acid
decrease uric acid synthesis
xanthin oxidase inhibitor
increase renal excretion of uric acid
uricosurics
T/F: uric acid lowering therapy are not to be used during acute gouty arthritis attack
True
xanthine oxidase inhibitors
allopurinol (first-line tx), febuxostat
reduce uric acid by impairing conversion of hypoxanthine to xanthine and xanthine to uric acid
xanthine oxidase inhibitor
xanthine oxidase inhibitors are effective in both _________________________________ of uric acid
overproducers and uncerexcretion
most widely prescribed agents for long-term prevention of recurrent gout attacks
xanthine oxidase inhibitors
a purine analog that inhibits xanthine oxidase resulting in a fall in plasma urate level and in the overall urate burden
allopurinol
Allopurinol is often the first-line agent for tx of ________________ in the period between attacks
chronic gout
it tends to prolong intercritical period and therapy is continued for years if not for life
allopurinol
potent and selective non-purine inhibitor of xanthine oxidase
febuxostat
probenecid, sulfinpyrazone, and lesinurad
uricosuric drugs
uricosuric agents discontinued in the US
sulfinpyrazone and lesinurad
uricosuric drugs increase renal clearance of uric acid by inhibiting the _____________________________________ of uric acid
postsecretory renal proximal tubular reabsorption
should be initiated in gouty px with underexcretion of uric acid when allopurinol or febuxostat is contraindicated
probenecid
probenecid can be used as monotherapy or in combination with a ____________________ (e.g., allopurinol or febuxostat)
xanthine oxidase inhibitor
canakinumab, anakinra, rilonacept
IL-1 receptor inhibitors
main proinflammatory cytokine responsible for the crystal-induced inflammation of gout
IL-1B
not yet FDA-approved for gout
IL-1 inhibitors
canakinumab, anakinra, rilonacept mode of admin
SC
