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
QUESTIONS 1 of 2 1 2 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI 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/LFemale: 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/mLFemale: 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/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative 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/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 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/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 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/minFemale: 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 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 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 ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + (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 (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 15% (6/40) 2 Colchicine 15% (6/40) 3 Allopurinol 18% (7/40) 4 Indomethacin 12% (5/40) 5 Probenecid 40% (16/40) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5