Gout Flashcards
What is gout
a clinical spectrum of diseases with:
elevated serum urate concentration (hyperuricemia)
recurrent attacks of acute arthritis w/ monosodium urate crystals in the synovial fluid
deposits of tophi in tissues around joints
interstitial renal disease
uric acid neprhosis
What are tophi
monosodium urate crystals that get deposited in tissues in and around joints
Define hyperuricemia
Men: 7+ mg
Women: 6+ mg
(hyperuricemia is an asymptomatic condition, but is necessary to diagnose gout)
How is uric acid produced
it is the last step in degradation of pruines
higher in humans than animals
We do not have uricase enzyme (converts uric acid into a more soluble allantoin
What is the physiology in a “gouty” joint
Synoviocytes phagocytize urate crystals and secrete inflammatory mediators
Mediators activate PMN and macrophages
Drugs used to treat gout target
inhibiting crystal phagocytosis and PMN/Macrophage release of inflammatory mediators
What causes overproduction of uric acid
not fully known.
suspected: enzyme P that is genetically determined, or, malignancy or myelo/lymphoproliferative disorder
What causes underexcretion of uric acid (more common)
Decrease in renal excretion of uric acid for unknown reason**
Overabundance tried to be eliminated through GI tract but it can’t all be
These are pruine rich foods, and should be avoided (5-100mg/3.5 oz serving)
asparagus bacon beef buillon calf tongue cauliflower chicken duck goose ham lamb kidney beans, lentils, lima beans, navy beans mushrooms oatmeal pork cod, crab, halibut, lobster, oyster, salmon, shrimp, snpper, trout, tuna spinach turkey
These foods have VERY high levels of pruines, definitely avoid! (1000mg/3.5 oz serving)
anchovies brain gravies kidney liver sardines sweetbreads
What drugs can induce hyperuricemia/gout
diuretics nicotinic acid salicylates ethanol pyrazinamide ethambutol cytotoxic drugs cyclosporine levodopa *know drug class or name of speciic drugs*
What is acute gout
attacks of joint inflammation, 3-10 days
80% of initial gout attacks are in 1 LE joint
MC affects first MTP (podagra- foot pain)
can mimic or co-exist w/ infection
DDx for gout is
infection FB fracture AVN atypical RA arthritis
What are the other tyoes of gout
Chronic: rheumatoid-like
Tophaceous: monosodium urate in soft tissues and joints
What is definitive Dx for gout
joint tap and microscopic exam for uric acid crystals
serum uric acid levels drop during an attack! that’s why you tap the joint
What is the clinical triad of gout
inflammatory monoarthritis
elevated serum uric acid level
response to colchicine
Goals in treatment of gout are
terminate acute atatck
prevent recurrent attacks
prevent complications w/ chronic depositions of urate crystals in tissues
anti-inflammatory prophylaxis of acute gout during initiation of urate lowering therapy
Drug therapy for gout includes
APAP
NSAIDS, ASA, cox-2 inhibitors, DMARDS
Acute gout: NSAIDs, Corticosteroids
Chronic: Colchicine, Probenecid, Allopurinol, Febuxostat
What agent is used to reduce pain quickly
Indomethacin!
What is the MOA of Colchicine
inhibition of microtubule assembly decreases macrophage migration and phagocytosis
Inhibits LT-B4= decreased inflammation
How should colchicine be used
acute: gout pain resolution IF started w/in 36 hours of attack
-acute attack, dose at 1.2 mg, then 0.6 mg in 1 hr
helps avoid gout attacks when used prophylactiaclly
ADE of colchicine include
dose dependent GI effects (diarrhea, nausea, vomiting)
reversible neuromyopathy
Toxicity: exacerbation of acute gout, hypersensitivity rxn
*Adjust dose when using CYP3A4 and P-glycoprotein inhibitors
Inhibits renal tubular secretion of methotrexate
How can corticosteroids be administered for gout treatment
Oral: methylprednisone dose pack
IM: give tramcinolone, but follow with oral prednisone or prednisolone
Intraarticular: only if 1-2 joints involved, combine with NSAIDs, colchicine, or oral corticosteroids
ADE of corticosteroids are
adrenal suppression growth inhibition muscle waisting osteoporosis salt retention glucose intolerance behavioral changes
What anti-inflammatory regimens can be used during initiation of urate lwoering therapy
Colchicine .6mg 1-2x day
Low dose NSAIDs w/ PPI
Prednisone
-whichever you choose, continue at least 6 months, or 3-6 months after you get to target serum uric acid
Xathine oxidase inhibitors can be use for
prophylaxis of recurrent gout attacks in both underexcreters and overproducers of uric acid
Allopurinol, Febuxostat
When should you initiate XOI (allopurinol or febuxostat)
2+ gout attacks per year
1+ tophi
CKD stage 2+
Hx of urolithiasis
How do you dose XOI
titrate to a goal seum urate lelel <6mg or <5mg if S/Sx persist at 6mg
What does xanthine oxidase do
It converts Xanthine to Uric acid
So if you inhibit this enxyme, then you will get less production of uric acid
What is the first like urate lowering therapy
Allopurinol (XOI)
Irreversibly* inhibits xanthine oxidase and lowers production of uric acid
Used in chronic gout* starting at 100mg/day (50mg/d if w/ CKD)
You can titrate up every 2-5 weeks (max dose 800)
ADE of Allopurinol are
pruritis, rash, elevated LFT
Acute hypersensitivity syndrome: highest risk in first few months (consider genetic testing in high risk koreans w/ CKD, Han chinese, or Thai)
Another first line urate lowering therapy is
Febuxostat (XOI)
Reversibly* inhibits xanthine oxidase and can be used in overproducers and underexcretors
Start at 40mg daily, monitor in 2 weeks; if uric acid isn’t <6mg, increase to 80mg
do NOT need to dose adjust in renal disease or hepatic impairment! (but unsure in pts w/ CrCl <30)
NEVER use Febuxostat with
Azathioprine
ADE of Febuxostat are
high LFT nausea arthralgias rash Toxicities: LFT, renal function
What is Probencid
Uricosuric therapy (increase excretion) Need to drink TONS of water to help flush system do NOT use if rCl <50, or Hx of urolithiasis
XOI + fenofibrate or losartan can be used to
augment uric acid excretion
Good in patients with other disorders
What is Pegloticase
A biologic for patients with refractory gout not responding to other Tx; it is essentially recombinant porcine-like uricase that metabolizes uric acid to allantoin
Can be use din overproducers and under-excretors
Heavy disease burden with chronic tophaceous disease
Lowers uric acid levels and reduces deposits of uric acid crystals in joints and soft tissue
What is Lesinurad
Inhibits function of transporter proteins involved in renal uric acid reabsorption and anion transfer= lowers serum uric acid levels and increases renal excretion of uric acid
Indications for using Lesinurad are
patients w/ hyperuricemia associated with gout who do not achieve target serum uric acid levels with conventional therapies
can be used in overproducers and underexcretors
Must use W/ XOI 2/2 risk of renal failure if used alone
ADE of Lesinurad are
acute gout attack during initiation HA GERD adverse cardiovascular fxn Renal function toxicity
What off label gout drugs target IL-1
Anakinra
Canakinumab
Rilonacept
What is Canakinumab
fully human anti-IL-1b MAB
rapid and sustained pain relief at 150mg subQ
safe to use in acute gout and gout prophylaxis
