Gout and Hyperuricemia

Question 1

NSAIDs MOA

Answer 1

Provide relief by inhibiting cyclooxygenase 2 (COX-2) mediated prostaglandin synthesis at the site of injury

Question 2

NSAIDs Drugs

Answer 2

Indomethacin
Naproxen
Sulindac

Question 3

Corticosteroids MOA

Answer 3

Decreases inflammatory response

• inhibits synthesis and release of cytokines with reduced activation of T cells and fibroblast proliferation
• inhibits pro-inflammatory transcription factors

Question 4

Corticosteroids Therapeutic Use

Answer 4

• For those who can’t tolerate NSAIDs
• For when the infection has been ruled out
• associated with rebound flares of acute gout
• may be given systematically for polyarticular attacks
• may be given intra articularly for monoarticular attacks

Question 5

NSAIDs Therapeutic Use

Answer 5

• Provide pain relief within 2-4 hours

- Treatment required for 7-14 days

Question 6

NSAID administration

Answer 6

• Treatment within 24 hours of symptoms: potent NSAID
• Days into attack: NSAID with lower side effects
• With improvements, cut dose in half
• treatment required for 7-14 days

Question 7

Colchicine MOA

Answer 7

• Selective inhibitor of microtubule assembly; reduces leukocyte migration and phagocytosis, thus decreasing inflammation
• Reduces inflammatory response to deposited crystals

Question 8

Colchicine Use

Answer 8

• Not an analgesic
• Does not affect renal excretion of uric acid
• Does not alter plasma solubility of uric acid
• Neither raises nor lowers serum uric acid

Question 9

Colchicine ADRs

Answer 9

• GI: Diarrhea, nausea, vomiting, abdominal pain
• Heme: anemia, leukopenia, neutropenia, thrombocytopenia, and aplastic anemia
• Hepatic: hepatomegaly, elevated liver enzymes
• Myopathy

Question 10

Colchicine DDI

Answer 10

Statins
Fibrates (gemfibrozil)
Digoxin

Question 11

Prophylatic Therapy

Answer 11

Should be initiated before the initiation of a hypouricemic agent and continued during the use of a hypouricemic agent (administer a small dose of colchicine or NSAID)

Question 12

What Patients should use Prophylatic Therapy?

Answer 12

• severe attacks of gouty arthritis
• a complicated course of uric acid nephrolithiasis
• a substantially elevated serum uric acid level (>10 mg/dl)
• 24 hr urinary excretion of uric acid or more than 1000 mg

Question 13

Uricosuric Therapy MOA

Answer 13

Antagonist at URAT 1 Transporter to block uric acid reabsorption: increases Uric Acid Excretion

Question 14

Patients that use Uricosuric Agents

Answer 14

• normal renal function (CrCl>50 mL/min)
• underexcrete uric acid
• negative history of nephrolithaisis
• NOT effective in overproducers

Question 15

Uricosuric Agent complications

Answer 15

may precipitate nephrolithiasis

Question 16

Xanthine Oxidase Inhibitor: Febuxostat

Answer 16

• Chronic management of Hyperuricemia

- No dose adjustment for patients with mild to moderate renal impairment

Question 17

Xanthine Oxidase Inhibitor: Febuxostat contraindications

Answer 17

Contraindicated with patients on azathioprine, mercaptopurine, or theophylline
-monitor liver function for elevations in transaminase

Question 18

Black Box warning for Febuxostat

Answer 18

• Increased risk of death
• higher rate of heart related death and death from all causes
• reserved for patients who failed or do not tolerate allopurinol

Question 19

Xanthine Oxidase inhibitor: Allopurinol MOA

Answer 19

Inhibits xanthine oxidase (stops hypoxanthine to xanthine to uric acid conversion) . which STOPs uric acid production

Question 20

Allopurinol DDIs

Answer 20

• Azanthioprine
• Mercaptopurine
• ACEI (steven johnson’s rash)
• Warfarin

Question 21

Allopurinol ADE

Answer 21

Hypersensitivity Reactions: fever, leukocytes, eosinophilia, skin rash, elevated SCr
Predisposing factors: renal dysfunction, thiazide diuretic, dose

Question 22

Allopurinol and high risk patients’ hypersensitivity

Answer 22

HLA-B*5801 screening for high risk population

• At risk: Korean descent with stage 3 or worse CKD
• Han Chinese or Thai descent

Question 23

Rasburicase MOA

Answer 23

Catalyzes oxidation of uric acid to readily eliminate metabolite (allatoin)

Question 24

Rasburicase is FDA approved for:

Answer 24

Hyperuricemia, due to malignancy, in patients with or patients with or at risk for tumor lysis syndrome

Question 25

Rasburicase Black Box Warning

Answer 25

Anaphylaxsis
Hemolysis
Methemoglobinemia

Question 26

Probenecid MOA

Answer 26

-Increases uric acid secretion by blocking URAT 1 transporter

Question 27

Probenecid Dosing and Side effects

Answer 27

• Dose: start low

- side effects: GI, hypersensitivity, watch for low dose aspirin

Question 28

Pegloticase MOA

Answer 28

• Catalyzes oxidation of uric acid fast to readily eliminate metabolite allatoin
• FDA approved
• 8 mg administered IV once every 2 weeks

Question 29

Pegloticase Black box warning

Answer 29

• Anaphylaxsis (6.5%)
• Infusion Reactions (26%)
• G6PD deficiency associated hemolysis and methemglobinemia

Question 30

Pegloticase administration

Answer 30

patients should be premedicated with anti histamtines and corticosteroids and treated in a health care setting

Question 31

Lesinurad MOA

Answer 31

Uric Acid Transporter inhibitor: stops uric acid reabsorption

Question 32

Lesinurad in treatment

Answer 32

used in combination with Xanthine Oxidase inhibitor for treatment of hyperuricemia
-do NOT start if creatinine clearance is below 45 mL/min

Question 33

When to use Antihyperuricemic therapy

Answer 33

• Patient has frequent acute attacks (more than 1-2/year)
• Clinical or Radiographic signs of chronic gouty joint disease
• Presence of Tophaceous Gout
• Evidence of urate nephrolithiasis

Question 34

Potential complication with Anti hyperuricemic agents

Answer 34

It may cause an attack or worsen it, so give a low dose NSAID or colchicine initially