Gout Flashcards
gout is
an arthritis associated w/ the presence of monosodium urate crystals (MSU) in synovial fluid or tissue leading to inflammatory reactions that causes intense pain, erythema and joint swelling
hyperuricemia
serum uric acid >7.0 mg/dL in M
serum level >6.0 mg/dL in F
should you tx asymptomatic pt with elevated serum uric acid concentration?
no
hyperuricemia secondary causes
- overproduction: purine rich diet, EToH, fructose, myeloproliferative disorders
-underexecretion: ethanol, cyclosporine, thiazides, furosemide, ethambutol, pyrazinamide, levodopa, niacin, low dose ASA, CTX agents, CKR
-wt, gender, HTN, etc.
non-pharm therapies
- correction or modification of underlying factors - SEE secondary causes
-meds, wt loss
-reduce dietary intake of purine-rich foods
-increase fluid intake
-decrease salt consumption
-joint rest/immobilization for 1-2d
-application of ice to affected area
for attacks of mild/moderate gout severity
6 of 10 on a 0-10 pain VAS particularly those involving 1 or a few small joints or 1 or 2 large joints
…monotherapy
in the absence of comorbidities
NSAID > colchicine > corticosteroids
must consider pt specific factors & commorbidities
NSAIDs
most effective if started w/i 1st 24hr of onset and continued for 24hr after resolution
NSAIDs should be avoided
active PUD
uncompensated CHF
uncontrolled HTN
severe renal impairment (<30-35ml/min)
NSAIDs are effective when given at full anti-inflammatory doses except
ASA and Tolmetin
COXibs
unclear risk/benefit ratio in acute gout
-option in pts w/ GI contraindications or intolerance to NSAIDs
colchicine
possesses no analgesic or uric acid-lowering effects
colchicine: acute dosing
1.2mg initially, then 0.6mg 1h later
total: 1.8mg over 1hr
colchicine: acute dosing contraindication
renal and hepatic dysfunction
elderly
frail
in severe renal impairment (CrCl <30mL/min) should not be repeated for 14 days
CrCl 30-80mL/min: no renal adj necessary
colchicine: place in therapy
-NSAID intolerance
-pts at risk for NSAID-induced gastropathy (active PUD)
-moderate CKD (w/ proper dose modifications)
-failed NSAID therapy
colchicine: ARDs & CIs
mostly GI (alopecia, malabsorption of vit b12, myopathy, myelosuppression)
-severe renal/hepatic impairment (neutropenia
-severe renal/hepatic impairment
- concomitant use of P-glycoprotein (P-gp) or strong CYP3A4 inhibitor in presence of renal or hepatic impairment
-severe cardiac / GI disease
corticosteroids
indicated w/ NSAIDs or colchicine contraindication (eg. renal impairment)
or
tx failure
corticosteroids: efficacy to NSAIDs
equally effective in acute gout tx
corticosteroids: use
systemically (PO/IV/IM) or by intraarticular injection
slower tapering of the glucocorticoid dose w/ extension of the course 10-14 days or even 21 days
corticosteroids: ARDS
-hyperglycemia
-HTN
-headache
-mood changes
-fluid retention
corticosteroids: precautions
-DM
-uncontrolled HTN
-severe infections
-active PUD
-severe cardiovascular disease (HF)
interleukin-1 (IL-1) inhibitors
anti-inflam agents in refractory gout or for pts who are unable to tolerate conventional therapy, such as NSAIDs, colchicine, or glucocorticoids, for acute attacks
***beneficial as 4th line therapy for acute gout due to their high cost and limited clinical experience
corticotropin
exogenous administration of IM adrenocorticotropic hormone (ATCH) stimulates production of corticosterone by the adrenal cortex
40IU given IM and repeated q24h as needed
combination therapy
in severe polyarticular attacks, particularly attacks involving multiple large joints
-colchicine may be used in combination w/ an NSAID or oral corticosteroid
-intraarticular corticosteroid injections may be used in combination w/ any other first0line agent (NSAID, colchicine, oral corticosteroid)
prophylaxis
-two or more gout attacks per year
-tophaceous gout
-joint damage seen on a radiograph
-uric acid nephrolithiasis/chronic kidney disease stage 2 or worse
prophylaxis: non-pharm
lose wt if obese
discon’t EToH
low-purine diets
dicon’t drugs
maintain hydration
prophylaxis: when to start
-during an acute gout attack only if anti-inflam tx is also initiated bc sudden shifts in SUA levels from mobilization of tissue urate stores may precipitate or exacerbate gouty arthritis
or
after resolution (4-6 wk) of acute attack; may use colchicine or low dose NSAIDs prophylactically upon initiation until [serum UA] returns to normal or max of 3-6 months
GIOP
most common secondary cause of OP and 3rd most common cause overall
American College of Rheumatology (ACR) recommends
oral bisphosphonate therapy for all patients age 40 and over at moderate-high of fx receiving glucocorticoids (prednisone 2.5 mg or more daily or equivalent) for 3 months+
xanthine oxidase inhibitors
allopurinol
-prevention & tx of gout associated w/ hyperuricemia
reduces the serum uric acid level while increasing the renal excretion of the more soluble oxypurine precursors
good for overproducers and underexcretors
1st-line therapy
xanthine oxidase inhibitors: reserved for hypersensitive, intolerable or had failure w/ allopurinol
febuxostat
several clinically significant DI
uricosurics
drug class
promote excretion of uric acid
eg. probenicic
best for underexcreators
probenicid C/I
hypersensitivity reactions
renal dysfunction
hx of kidney stones
acute attack
overproducers of uric acid
may share allergenicity w/ other classes of sulfonamide drugs
uric acid transporter 1 (URAT) and organic anion transporter 4 (OAT) inhibitor
Lesinurad
American College of Rheumatology states that serum urate concentration in gout pts s/b reduced sufficiently to result in durable improvement in s&S of teh disease and recommends a target serum urate concentration of
<6 mg/dL (or <5mg/dL if nec to achieve such clinical improvements
-use in combination w/ xanthine oxidase inhibitor in pts who have no attained target serum uric acid concentratins
-do no use as monotherapy
losartan
inc uric acid secretion and urinary pH
option for hypertensive pts w/ gout
fibrates
increases uric acid secretion
option for select pts w/ hypertriglyceridemia
colchicine
daily use (0.6-1.2mg/day) for prophylaxis
-renal dosage adj required w/ CrCl <30mL/min
herbal treatments
no acceptable clinical evidence of efficacy or safety
pegloticase
FDA-approved tx of chronic refractory gout
8mg IV q2w
start on prophylaxis w/ colchicine or NSAID when initiating therapy
xanthine oxidase inhibitors: black box warning
must pretreat w/ antihistamines and corticosteroids
