Exam 4 - Gout

Question 1

What are risk factors for gout? (6)

Answer 1

age (less for females post-menopause), sex (males), co-morbid conditions, diet, meds, renal urate transporter genotypes

Question 2

What is uric acid a metabolite of?

Answer 2

purines (via diet or tissue breakdown)

Question 3

What enzyme do humans not have in the purine breakdown pathway? What does it produce?

Answer 3

urase; allantoin (from uric acid)

Question 4

Explain the pathophsyiology of hyperuricemia and gout?

Answer 4

uric acid (at saturating concentrations) precipitates into crystals and these deposit in joints to trigger immune response

Question 5

What comorbidities promote hyperuricemia? (7)

Answer 5

DM, CKD, CHF, HTN, hyperlipidemia, obesity, organ transplantation

Question 6

What foods are hyperuricemic? (5)

Answer 6

meat, seafood, beer and liquor, soft drinks, fructose

Question 7

What foods are uricosuric? (3)

Answer 7

coffee, dairy, vitamin C

Question 8

What medications are hyperuricemic? (4)

Answer 8

thiazide diuretics, loop diuretics, nicotinic acid, aspirin (<1 g/day)

Question 9

What medications are uricosuric? (2)

Answer 9

losartan, fenofibrate

Question 10

What is podagra (classic acute gout)?

Answer 10

a gout flare (attack) that generally affects the first metatarsophalangeal joint

Question 11

What are tophi?

Answer 11

masses of urate deposits in bone, cartilage, joints or tissues

Question 12

Which NSAIDs have FDA-approved labeling for gout? (3)

Answer 12

indomethacin, naproxen, and sulindac

Question 13

What are contraindications for NSAIDs? (5)

Answer 13

renal insufficiency/failure, bleeding disorders/anticoagulated patients, peptic ulcer disease, CHF, age 75+

Question 14

What is the MOA of colchicine?

Answer 14

inhibition of beta-tubulin polymerization into microtubules, hinders neutrophil chemotaxis

Question 15

How is colchicine dosed (general)?

Answer 15

1.2 mg (2 tabs) PO, then 0.6 mg 1 hr later

Question 16

What are AEs of colchicine? (4)

Answer 16

GI (diarrhea), hematologic abnormalities, rhabdomyolysis (in renal dysfunction and elderly), myopathy (concomitant use of 3A4 and P-gp inhibitors, statins and fibrates)

Question 17

What are contraindications for colchicine? (2)

Answer 17

CrCl <30 mL/min, hepatic impairment

Question 18

What are examples of strong CYP3A4 inhibitors (4)

Answer 18

clarithromycin, darunavir/ritonavir, itraconazole, ketoconazole

Question 19

What are examples of moderate CYP3A4 inhibitors? (4)

Answer 19

diltiazem, verapamil, erythromycin, fluconazole

Question 20

What are examples of P-glycoprotein inhibitors? (3)

Answer 20

cyclosporine, amiodarone, ranolazine

Question 21

What is the colchicine regimen for acute gout flares while on a strong CYP3A4 inhibitor?

Answer 21

0.6 mg, then 0.3 mg 1 hr later

Question 22

What is the colchicine regimen for acute gout flares while on a moderate CYP3A4 inhibitor?

Answer 22

1.2 mg , then again after at least 3 days

Question 23

What is the colchicine regimen for acute gout flares while on a P-gp inhibitor?

Answer 23

0.6 mg, then again after at least 3 days

Question 24

What is the colchicine regimen for gout flare prophylaxis while on a strong CYP3A4 inhibitor?

Answer 24

0.3 mg eod to qd

Question 25

What is the colchicine regimen for gout flare prophylaxis while on a moderate CYP3A4 inhibitor?

Answer 25

0.3-0.6 mg qd

Question 26

What is the colchicine regimen for gout flare prophylaxis while on a P-gp inhibitor?

Answer 26

0.3 mg eod to qd

Question 27

What corticosteroid is used IA?

Answer 27

triamcinolone

Question 28

How are corticosteroids in large (knee), medium (wrist, ankle, elbow), and small (toe, finger) joints dosed, respectively?

Answer 28

40, 30, and 10 mg

Question 29

What are AEs of corticosteroids? (4)

Answer 29

leukocytosis, hyperglycemia, increased appetite, mood changes

Question 30

What are the goals of chronic therapy in gout? (2)

Answer 30

prevent future attacks and hyperuricemic sequelae (arthropathy, tophus formation, joint damage) by maintaining SUA <6.0

Question 31

What is the MOA of allopurinol and febuxostat?

Answer 31

xanthine oxidase inhibitor (prevents conversion of purines to uric acid)

Question 32

What are AEs of allopurinol? (2)

Answer 32

rash (potential SJS), DRESS

Question 33

What are DDIs for allopurinol? (7)

Answer 33

warfarin, 6-mercaptopurine/azathioprine/theophylline, amox/ampicillin, thiazides, ACE-i

Question 34

How is allopurinol dosed?

Answer 34

50-100 mg/day titrated up to achieve SUA <6 mg/dL

Question 35

How is febuxostat dosed?

Answer 35

40 mg/day up to 80 to achieve SUA <6 mg/dL

Question 36

What are AEs of febuxostat? (3)

Answer 36

HA/dizziness, arthralgias, GI

Question 37

What is a boxed warning for febuxostat?

Answer 37

cardiovascular death

Question 38

What is a contraindication for febuxostat?

Answer 38

concurrent 6-MP/azathioprine/theophylline

Question 39

What is the MOA of probenecid?

Answer 39

competitive inhibitor for reabsorption of uric acid at proximal convoluted tubule

Question 40

How is probenecid dosed?

Answer 40

250 mg bid, up to 500 mg

Question 41

What are contraindications for probenecid? (2)

Answer 41

CrCl <50 mL/min, Hx of nephrolithiasis

Question 42

What are DDIs for probenecid? (4)

Answer 42

penicillin, methotrexate, carbapenems (dori/meropenem), salicylates

Question 43

What is the MOA of pegloticase?

Answer 43

pegylated recombinant uricase substitute

Question 44

What is a boxed warning for uricase agents (pegloticase)?

Answer 44

infusion-related reactions

Question 45

What are the indications for chronic pharmacologic gout therapy?

Answer 45

1+ subcutaneous tophi, radiographic evidence of gout damage; or 2+ flares/year

Question 46

When else might one consider chronic pharmacologic gout therapy? (4)

Answer 46

Hx of >1 attack (w/<2/year), those with first flare who have CKD Stage 3+, [UA] >9 mg/dL, urolithiasis

Question 47

What is the goal serum urate level?

Answer 47

<6 mg/dL

Question 48

What are first-line for chronic pharmacologic gout therapy? (2)

Answer 48

low-dose colchicine or NSAIDs

Question 49

What is second-line for chronic pharmacologic gout therapy?

Answer 49

low-dose prednisone/olone

Question 50

How long should chronic pharmacologic gout therapy be? (3)

Answer 50

at least 6 months, OR achieving target serum and 3 months (no tophi) or 6 months (1+ tophi)

Question 51

What is first-line for acute pharmacologic gout therapy? (3)

Answer 51

NSAIDs, systemic corticosteroids, colchicine

Question 52

If patient is already on prophylactic colchicine during a gout flare?

Answer 52

if within 14 days, use NSAID or corticosteroid, otherwise use colchicine

Question 53

When should intraarticular corticosteroids be considered for gout flares?

Answer 53

1-2 large joint involvements

Question 54

What medications should not be co-administered in gout? (2)

Answer 54

NSAIDs and steroids