Exam 4 - Gout Flashcards
What are risk factors for gout? (6)
age (less for females post-menopause), sex (males), co-morbid conditions, diet, meds, renal urate transporter genotypes
What is uric acid a metabolite of?
purines (via diet or tissue breakdown)
What enzyme do humans not have in the purine breakdown pathway? What does it produce?
urase; allantoin (from uric acid)
Explain the pathophsyiology of hyperuricemia and gout?
uric acid (at saturating concentrations) precipitates into crystals and these deposit in joints to trigger immune response
What comorbidities promote hyperuricemia? (7)
DM, CKD, CHF, HTN, hyperlipidemia, obesity, organ transplantation
What foods are hyperuricemic? (5)
meat, seafood, beer and liquor, soft drinks, fructose
What foods are uricosuric? (3)
coffee, dairy, vitamin C
What medications are hyperuricemic? (4)
thiazide diuretics, loop diuretics, nicotinic acid, aspirin (<1 g/day)
What medications are uricosuric? (2)
losartan, fenofibrate
What is podagra (classic acute gout)?
a gout flare (attack) that generally affects the first metatarsophalangeal joint
What are tophi?
masses of urate deposits in bone, cartilage, joints or tissues
Which NSAIDs have FDA-approved labeling for gout? (3)
indomethacin, naproxen, and sulindac
What are contraindications for NSAIDs? (5)
renal insufficiency/failure, bleeding disorders/anticoagulated patients, peptic ulcer disease, CHF, age 75+
What is the MOA of colchicine?
inhibition of beta-tubulin polymerization into microtubules, hinders neutrophil chemotaxis
How is colchicine dosed (general)?
1.2 mg (2 tabs) PO, then 0.6 mg 1 hr later
What are AEs of colchicine? (4)
GI (diarrhea), hematologic abnormalities, rhabdomyolysis (in renal dysfunction and elderly), myopathy (concomitant use of 3A4 and P-gp inhibitors, statins and fibrates)
What are contraindications for colchicine? (2)
CrCl <30 mL/min, hepatic impairment
What are examples of strong CYP3A4 inhibitors (4)
clarithromycin, darunavir/ritonavir, itraconazole, ketoconazole
What are examples of moderate CYP3A4 inhibitors? (4)
diltiazem, verapamil, erythromycin, fluconazole
What are examples of P-glycoprotein inhibitors? (3)
cyclosporine, amiodarone, ranolazine
What is the colchicine regimen for acute gout flares while on a strong CYP3A4 inhibitor?
0.6 mg, then 0.3 mg 1 hr later
What is the colchicine regimen for acute gout flares while on a moderate CYP3A4 inhibitor?
1.2 mg , then again after at least 3 days
What is the colchicine regimen for acute gout flares while on a P-gp inhibitor?
0.6 mg, then again after at least 3 days
What is the colchicine regimen for gout flare prophylaxis while on a strong CYP3A4 inhibitor?
0.3 mg eod to qd
What is the colchicine regimen for gout flare prophylaxis while on a moderate CYP3A4 inhibitor?
0.3-0.6 mg qd
What is the colchicine regimen for gout flare prophylaxis while on a P-gp inhibitor?
0.3 mg eod to qd
What corticosteroid is used IA?
triamcinolone
How are corticosteroids in large (knee), medium (wrist, ankle, elbow), and small (toe, finger) joints dosed, respectively?
40, 30, and 10 mg
What are AEs of corticosteroids? (4)
leukocytosis, hyperglycemia, increased appetite, mood changes
What are the goals of chronic therapy in gout? (2)
prevent future attacks and hyperuricemic sequelae (arthropathy, tophus formation, joint damage) by maintaining SUA <6.0
What is the MOA of allopurinol and febuxostat?
xanthine oxidase inhibitor (prevents conversion of purines to uric acid)
What are AEs of allopurinol? (2)
rash (potential SJS), DRESS
What are DDIs for allopurinol? (7)
warfarin, 6-mercaptopurine/azathioprine/theophylline, amox/ampicillin, thiazides, ACE-i
How is allopurinol dosed?
50-100 mg/day titrated up to achieve SUA <6 mg/dL
How is febuxostat dosed?
40 mg/day up to 80 to achieve SUA <6 mg/dL
What are AEs of febuxostat? (3)
HA/dizziness, arthralgias, GI
What is a boxed warning for febuxostat?
cardiovascular death
What is a contraindication for febuxostat?
concurrent 6-MP/azathioprine/theophylline
What is the MOA of probenecid?
competitive inhibitor for reabsorption of uric acid at proximal convoluted tubule
How is probenecid dosed?
250 mg bid, up to 500 mg
What are contraindications for probenecid? (2)
CrCl <50 mL/min, Hx of nephrolithiasis
What are DDIs for probenecid? (4)
penicillin, methotrexate, carbapenems (dori/meropenem), salicylates
What is the MOA of pegloticase?
pegylated recombinant uricase substitute
What is a boxed warning for uricase agents (pegloticase)?
infusion-related reactions
What are the indications for chronic pharmacologic gout therapy?
1+ subcutaneous tophi, radiographic evidence of gout damage; or 2+ flares/year
When else might one consider chronic pharmacologic gout therapy? (4)
Hx of >1 attack (w/<2/year), those with first flare who have CKD Stage 3+, [UA] >9 mg/dL, urolithiasis
What is the goal serum urate level?
<6 mg/dL
What are first-line for chronic pharmacologic gout therapy? (2)
low-dose colchicine or NSAIDs
What is second-line for chronic pharmacologic gout therapy?
low-dose prednisone/olone
How long should chronic pharmacologic gout therapy be? (3)
at least 6 months, OR achieving target serum and 3 months (no tophi) or 6 months (1+ tophi)
What is first-line for acute pharmacologic gout therapy? (3)
NSAIDs, systemic corticosteroids, colchicine
If patient is already on prophylactic colchicine during a gout flare?
if within 14 days, use NSAID or corticosteroid, otherwise use colchicine
When should intraarticular corticosteroids be considered for gout flares?
1-2 large joint involvements
What medications should not be co-administered in gout? (2)
NSAIDs and steroids
