Updated: 4/23/2019

Gout Drugs

Topic
Review Topic
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Questions
2
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Evidence
1
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Overview

Snapshot
  • A 50-year-old man presents 4 months after an acute gout flare to his primary care physician. Since then, he has had 2 more episodes of minor flares that resolved on its own. He reports wanting better control of this disease. His physician describes several options for chronic gout and suggests allopurinol as a good first-line option.
Introduction
  • Chronic gout drugs
    • mechanism of action
      • prevents the build up of uric acid
    • drugs
      • allopurinol
      • febuxostat
      • pegloticase
      • probenecid
  • Acute gout drugs
    • mechanism of action
      • reduces inflammation
    • drugs
      • nonsteroidal anti-inflammatory drugs (NSAIDs)
      • glucocorticoids (oral, intra-articular, and parenteral)
      • colchicine
  • Drugs to avoid
    • low-dose salicylates
      • decreases uric acid excretion, which may precipitate gout
Allopurinol
  • Mechanism of action
    • competitive inhibition of xanthine oxidase, which decreases production of urate 
  • Clinical use
    • chronic gout
    • prevention of urate nephropathy from tumor lysis syndrome in lymphoma and leukemia
  • Toxicity
    • ↑ accumulation of azathioprine and 6-mercaptopurine (MP)
      • both are metabolized by xanthine oxidase
    • drug rash
Febuxostat
  • Mechanism of action
    • inhibition of xanthine oxidase
  • Clinical use
    • chronic gout
  • Toxicity
    • ↑ accumulation of azathioprine and 6-MP
    • some hepatotoxicity
Pegloticase
  • Mechanism of action
    • pegloticase is a recombinant uricase
      • catalyzes metabolism of uric acid to allantoin, which is more water-soluble
  • Clinical use
    • chronic gout
  • Toxicity
    • risk of new gout flare
    • infusion reactions
Probenecid
  • Mechanism of action
    • inhibition of proximal convoluted tubule resorption of uric acid
  • Clinical use
    • chronic gout
  • Toxicity
    • uric acid calculi
      • this should only be used in uric acid underexcreters and should be avoided in patients who are uric acid overproducers 
      • a history of prior uric acid stones is a contraindication for initiating this agent
    • prolonged penicillin serum levels
      • inhibition of proximal convoluted tubule secretion of penicillin
Colchicine
  • Mechanism of action
    • inhibition of microtubule polymerization by binding to tubulin, which impairs neutrophil chemotaxis and degranulation and decreases inflammation
  • Clinical use
    • acute and chronic gout
  • Toxicity
    • gastrointestinal irritation
 

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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
Calculator

(M1.MK.4666) A 54-year-old male has a history of gout complicated by several prior episodes of acute gouty arthritis and 3 prior instances of nephrolithiasis secondary to uric acid stones. He has a serum uric acid level of 11 mg/dL (normal range 3-8 mg/dL), a 24 hr urine collection of 1300 mg uric acid (normal range 250-750 mg), and a serum creatinine of 0.8 mg/dL with a normal estimated glomerular filtration rate (GFR). Which of the following drugs should be avoided in this patient? Review Topic

QID: 107094
1

Naproxen

16%

(6/38)

2

Colchicine

16%

(6/38)

3

Allopurinol

18%

(7/38)

4

Indomethacin

13%

(5/38)

5

Probenecid

37%

(14/38)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(M1.MK.4740) A 45-year-old male presents to the emergency room for toe pain. He reports that his right great toe became acutely painful, red, and swollen approximately five hours prior. He has had one similar prior episode six months ago that resolved with indomethacin. His medical history is notable for obesity, hypertension, and alcohol abuse. He currently takes hydrochlorothiazide (HCTZ). On physical examination, his right great toe is swollen, erythematous, and exquisitely tender to light touch. The patient is started on a new medication that decreases leukocyte migration and mitosis, and his pain eventually resolves; however, he develops nausea and vomiting as a result of therapy. Which of the following underlying mechanisms of action is characteristic of this patient’s new medication? Review Topic

QID: 108658
1

Inhibits microtubule polymerization

35%

(84/241)

2

Prevents conversion of xanthine to uric acid

32%

(77/241)

3

Decreases phospholipase A2-induced production of arachidonic acid

6%

(14/241)

4

Decreases cyclooxygenase-induced production of prostaglandins

20%

(49/241)

5

Metabolizes uric acid to water-soluble allantoin

4%

(10/241)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1
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