Gout Flashcards
What is gout?
inflammatory process in response to crystallization of monosodium urate in articular and non-articular tissues
hyperuricemia - uric acid level > 6.8 mg/dL AND symptomatic (can have hyperuricemia w/o sx or gout, so we don’t treat)
Epidemiology
men more likely to be affefcted
individual factors that may influence development of gout: genetics, dietary intake, socioeconomic factors
Pathophysiology
uric acid is main end product in purine degradation
allantoin is a soluble byproduct from uric acid breakdown
uric acid concentrations influenced by overproduction or underexcretion
Hyperuricemia -overproduction
regulatory enzyme variability, cytotoxic medications, increase dietary intake of purines, chronic alcohol intake
Hyperuricemia - underexcretion
dehydration, insulin resistance, acute alcohol intake, meds
Medications
diuretics (loops and thiazides), cytotoxic drugs, salicylates (<2g/day)
Risk factors
male, post-menopausal women (estrogen helps with excretion of uric acid), elderly, obesity, diet and alcohol intake, sedentary lifestyle, renal impairment
Acute gouty arthritis presentation
acute, inflammatory monoarthritis
podagra - first metatarsal joint often involved
uric acid can deposit elsewhere: fingers or wrist, cartilage or tendons, kidneys
s/sx: fever, intense pain, erythema, warmth, edema, and inflammation of affected joints
Lab tests
elevated uric acid > 6.8 mg/dL
WBC > 11,000cell/uL (could be an infection, use to rule out)
Complications
tophi - deposits of monosodium urate
nephrolithiasis - kidney stones
gouty nephropathy - acute and chronic kidney disease
Diagnosis
synovial fluid aspiration (not feasible)
in clinical practice use: monoarticular involvement, previous episodes, rapid onset of pain, swelling, and erythema, risk factors
Treatment goals
terminate acute attack
prevent recurrent attacks of gouty arthritis
prevent complications associated with chronic deposition or urate crystals in joints and tissues
patient education
Treatment approach
treatment of pain and inflammation (acute tx)
use of urate-lowering therapy to prevent recurrence (chronic treatment)
anti-inflammatory prophylaxis
Non-pharmacologic therapy
modification of risk factors over time
applying ice to the affected area to reduce pain
no supplements have shown benefit
Pharmacologic therapy for acute treatment
NSAIDs, corticosteroids, colchicine
NSAIDs
MOA: inhibits COX1 and 2 and decreases prostaglandin synthesis, thus decreasing inflammation
effective and have minimal toxicity short term
NSAIDs meds
indomethacin, naproxen, ibuprofen, sulindac
early initiation is key!
NSAID AEs
GI effects, kidney injury, CV effects, CNS effects, bleeding risk
Corticosteroids
MOA: decreases inflammation by suppression of leukocytes, reverses increased capillary permeability, and suppresses the immune system
Oral corticosteroids
methylprednisolone
prednisone
IM corticosteroids
triamcinolone
methylprednisolone
then follow with anti-inflammatory agent (NSAID, PO corticosteroid) b/c might have rebound pain
Intra-articular corticosteroids
triamcinolone
then follow with anti-inflammatory agent (NSAID, PO corticosteroid)
Corticosteroid tapering
prednisone: 0.5mg/kg daily for 5-10 days followed by abrupt discontinuation
0.5mg/kg daily for 2-5 days followed by taper for 7-10 days
Corticosteroid AEs
increased BG, anxiety and restlessness, GI upset, insmonia, fluid retention, BP elevation
Corticosteroid considerations
taper PO courses, limit treatment duration, increased risk of GI bleed and peptic ulcer disease, close monitoring of diabetes, avoid IA injection if suspect infection
Colchicine
MOA: disrupts cytoskeletal functions by inhibiting beta-tubulin polymerization into microtubules, thus preventing the activation, degranulation, and migration of neutrophils associated with gout sx
Colchicine recommended to administer
within 24hrs of acute attack (if longer, tons of WBCs + neutrophils already there and working)
oral capsule, tablet, and solution
Colchicine dosing
day 1: 1.2mg PO once, then 0.6mg one hour later
day 2+: 0.6 mg BID until attack resolves
Colchicine AEs
N/V/D
neutropenia, axonal neuromyopathy
Colchicine renal dose adjustments
CrCl >/= 30 mL/min: no adjustment required
CrCl < 30 mL/min: 1.2mg at onset, 0.6 mg 1 hr later (once) do NOT follow up with 0.6mg BID after
dialysis: single 0.6mg dose
treatment course should be repeated no more than once every 2 weeks
Colchicine inadequate initial response
<50% improvement in pain in 24hrs: switch agents, add a 2nd recommended agent - try to avoid NSAIDs with PO corticosteroids together
Colchicine clinical pearl
pill-in-pocket method: pts who can recognize gout sx onset use aborptive agents like NSAIDs or colchicine
recommended to decrease time to treatment for adequate pain control and response
do NOT use in pts who have frequent attacks
Chronic gout management - nonpharmacologic therapy
weight loss if overweight/obese
dietart approaches to stop HTN - may lower uric acid ~1mg/dL; DASH diet, avoid foods high in saturated fats and sweetened beverages/foods
alcohol restriction
limit restriction of purine-rich foods: high fructose corn syrup, organ meats and seafood
Chronic gout management: urate lowering therapy - indications to start
frequent gout flares >/= 2 per year; >/= 1 tophus; radiographic evidence of damage attributable to gout; > 1 prior flare, but infrequent (< 2/yr); pts experience 1st flare in the presence of 1 of the following: CKD stage 3-5, uric acid > 9mg/dL, urolithiasis
Who is not a candidate for ULT?
asymptomatic hyperuricemia with no prior gout flare or tophi
1st gout attack without risk factors
ULT initiation/duration of therapy
initiation: either wait 2 weeks after acute attack or initiate during an acute attack
duration: indefinitely!
ULT monitoring
serum uric acid at baseline and periodically
treat to target of serum uric acid < 6mg/dL
Chronic gout pharmacologic therapy
1st line: xanthine oxidase inhibitors
2nd line: uricosurics
3rd line: uricase agents
Xanthine oxidase inhibitors MOA
reduces uric acid by impairing the ability of xanthine oxidase to convert hypoxanthine to xanthine and therefore to uric acid (inhibits enzyme that forms uric acid)
Xanthine oxidase inhibitor meds
allopurinol: titrate every 2-4 wks in </=100 increments as needed to achieve uric acid < 6mg/dL
febuxostat
Allopurinol renal impairment
eGFR > 60: no adjustment
eGFR </= 60: initial dose 50 mg
titrate slowly and in small increments (can still achieve higher doses)
Allopurinol AEs
skin rash, HA, urticaria, hepatotoxicity, hypersensitivity rxn - stevens johnson syndrome and toxic epidermal necrolysis (risk factors = female, age >60, high initial doses, CKD, CV disease) test for HLA-B*5801 allele to see if + in pts with southeast asian or african decent
Allopurinol monitoring and counseling
monitor: uric acid q2-5wks while titrating, every 6mo when stable; renal fx; LFTs
counsel: drink plenty of fluids, take this med even when you do not have gout sx!
Febuxostat
black box warning: increased CV mortality
this med reserved for pts unable to tolerate allopurinol
AEs: nausea, arthralgias, rash
renal dosing adjusment
Uricosuric drugs MOA
increase renal clearance of uric acid by inhibiting post-secretory renal proximal tubular reabsorption of uric acid
Uricosuric drug
probenecid: titrate q1-2wks
Probenecid
AEs: GI irritation, rash, urolithiasis (contraindicated in pts with history)
cautions: G6PD deficiency (increased risk of hemolytic anemia), not recommended in eGFR < 60
Uricase agents MOA
recombinant form of urate-oxidase enzyme (uricase) converts uric acid to the more soluble metabolite, allantoin (able to be excreted)
Uricase agents med
pegloticase - used in severe gout and hyperuricemia: >/=3 gout flares within 18mo, >/=1 tophi, joint damage due to gout
IV infusion (infused over 2hrs every 2wks)
Pegloticase
black box warning: anaphylaxis and infusion related rxns; G6PD deficiency associated hemolysis and methemoglominemia
AEs: constipation, N/V, chest pain, nasopharyngitis
pearls: immunogenicity: pt may develop antibodies that result in lack of efficacy of drug
Other ULT meds
fenofibrate
losartan
Fenofibrate
MOA: increases clearance of hypoxanthine and xanthine
NOT recommended to switch hyperlipidemia agents for gout benefits
Losartan
MOA: inhibits tubular reabsorption of uric acid and increases urinary excretion; reduces stone formation by alkalinizing the urine
preferred agent in pts with gout AND HTN
Gout attack prophylaxis
use when initiating ULT –> goal to decrease incidence of gout attacks –> duration recommended for 1st 3-6mo of ULT initiation
Gout attack prophylaxis therapy
NSAIDs, prednisone, colchicine
duration: during initiaiton of ULT, 3-6mo or longer if indicated
Prophylaxis: colchicine dosing
CrCl >/=30 mL/min: 0.6 mg once or twice daily (lower than acute dosing)
CrCl < 30 mL/min: consider alternate therapy, if not able to: 0.3mg daily, if on dialysis then 0.3mg twice weekly
