Drugs for Gout, Hyperuricemia - Fitz

Question 1

Foods that can increased uric acid

Answer 1

Proteins, alcohol, fructose

Question 2

Drug goal for uric acid level

Answer 2

Under 6 mg/dL

Question 3

Determinants of gout accumulation (4)

Answer 3

• Blood pH (low = more)
• Temperature (low = more)
• Hydration (night = joint dehyd.)
• Altered matrix, exposed cartilage, debris, etc.

Question 4

3 ways to treat gout (w/ drugs)

Answer 4

Anti-inflammatories
- Colchicine, NSAIDs

Re-uptake (URAT1) inhibitor
- Probenecid, Sulfinpyrazone

Synthesis inhibitor
- Allopurinol, Febuxostat

Question 5

Advanced or resistant cases of gout…treatment?

MoA?

Answer 5

Uricosolytics (urate oxidase)
- Pegloticase, Rasburicase

Metabolizes the crystals in the blood

Question 6

Colchicine - MoA

Answer 6

Binds tubulin and depolymerizes microtubules – disrupts granulocyte function, inhibits LTB4 formation

Question 7

Acute, sporadic gout attacks…only good treatment?

Answer 7

NSAIDs (often more than the OTC dose)

Question 8

Acute, sporadic gout attacks. NSAIDs are contraindicated. Treatment?

MoA?

Does not decrease ___ or ___

Side effect?

Answer 8

Colchicine

Prevents chemotaxis and degranulation of PMNs

Uric acid levels, inflammation

GI toxicity (diarrhea, abd pain)

Question 9

Gout, problems w/ blood sugar, DM, HTN, risks for osteoporosis…what to avoid?

If not contraindicated, when are they used?

Answer 9

Steroids

2+ joint involved and colchicine is contraindicated or ineffective

Question 10

1st line urate lowering therapy

Can add what if needed?

Severe disease or failure?

Answer 10

XO inhibitor

Uricosuric (Probenecid)

Uricosolytic (urate oxidase)

Question 11

Allopurinol…what accumulates?

Answer 11

Hypoxanthine

Question 12

Patient started on urate lowering therapy, presents soon after w/ gout attacks. What’s up?

***How to prevent?

Answer 12

Paradox - can cause increased solubilization when starting therapy

Give Colchicine or an NSAID when starting on urate lowering therapy

Question 13

**Drugs to avoid if giving Allopurinol or Febuxostat? (3)

Toxicities?

Why?

Answer 13

• 6-Mercaptopurine - marrow suppression
• Azathioprine - marrow suppression
• Theophylline - CNS agitation

These are based off of Xanthine structure, so will cause excess accumulation and toxicity

Question 14

Patient has HLA-B*5801…so?

Populations?

Answer 14

Potential for SEVERE hypersensitivity to allopurinol…must get genetic testing

Han Chinese, Thai descent

Question 15

With probenacid vs. w/o probenacid, how much uric acid is excreted in urine?

Answer 15

Without = 10%

With = 20%

Question 16

Probenacid - side effect

Answer 16

Nephrolithiasis or uric acid nephropathy

Question 17

Patient is taking Probenacid. What other drugs could cause issues? (2) Why (for each)?

Answer 17

Aspirin (low level) – competes for organic acid transporters at basolateral side, preventing excretion of uric acid

Diuretics (loop, thiazide) – dehydration can lead to crystallization

Question 18

Patient w/ gout due to tumor lysis syndrome. Treatment?

Answer 18

Pegloticase (IV)

Question 19

Pegloticase/Raasburicase…will see increased levels of what?

Answer 19

Allantoin (breakdown product)

Question 20

Why does high-dose Aspirin not cause increased uric acid?

Answer 20

Blocks ALL organic acid transporters, thus can’t be reabsorbed into the blood following the 100% glomerular filtration