Updated: 4/14/2019

Loop Diuretics

Topic
Review Topic
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0
Questions
7
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0
Evidence
5
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0
Overview
 

 
Snapshot
  • A 72-year-old woman with a history of congestive heart failure, hypertension, and myocardial infarction presents with dyspnea on exertion and orthopnea. She does not have chest pain and denies any fever or chills. She does note increased swelling of her ankles but denies any other changes. Physical exam is notable for inspiratory crackles on lung ausculation and 2+ pitting edema on the bilateral lower extremities. Her physician increases the dose of one of her medications. One week later, she presents with muscle weakness and has an electrocardiogram that shows U waves. Serum electrolytes are drawn and her potassium level is found to be 2.8 mEq/L.
Furosemide
  • Mechanism 
    • blocks Na+/K+/2Cl- (NKCC) cotransport system in the thick ascending limb of the loop of Henle
      • these electrolytes remain in the tubular lumen which
        • prevents the formation of the medullary concentration gradient
        • leads to less water reabsorption in the distal tubule
      • blocking the NKCC cotransporter also prevents potassium back leaking into the lumen
        • this results in magnesium and calcium loss
      • increased sodium delivery to the collecting duct leads to increased exchange with potassium and hydrogen
  • Clinical use
    • edema
      • etiology
        • decompensated congestive heart failure (CHF)
        • pulmonary edema
        • ascites in the setting of cirrhosis
        • nephrotic syndrome
    • hypertension
      • not first-line
      • used in patients with concurrent hypertension and edema
    • hypercalcemia
    • anion overdose
  • Toxicity
    • ototoxicity
      • worsened with concurrent use of aminoglycosides 
    • electrolyte changes 
      • hypokalemia
      • hypomagnesemia
      • rarely, hypocalcemia
      • contraction alkalosis
      • hyperuricemia resulting in gout
    • dehydration
    • sulfa allergy
    • interstitial nephritis
    • enhanced toxicity with digoxin and lithium
  • Miscellaneous
    • nonsteroidal anti-inflammatory drugs (NSAIDs) can decrease the response to loop diuretics due to decreased renal blood flow (RBF)
Ethacrynic acid
  • Mechanism
    • similar action to furosemide
      • blocks NKCC cotransport system
    • non-sulfa drug (phenoxyacetic acid derivative)
  • Clinical use
    • diuresis in patients allergic to sulfa drugs
  • Toxicity
    • more ototoxic than furosemide
 

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Questions (7)
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
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(M1.RL.63) A 68-year-old male with congestive heart failure recently had his medication regiment adjusted to better control his hypertension. Three weeks later, laboratory analysis shows his serum calcium and magnesium levels have both decreased. The diuretic used in this patient acts predominantly on which nephron segment: Review Topic

QID: 101017
1

Proximal tubule

9%

(18/190)

2

Descending loop of Henle

4%

(8/190)

3

Thick ascending loop of Henle

66%

(126/190)

4

Distal tubule

17%

(32/190)

5

Cortical collecting duct

3%

(5/190)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.RL.80) A 67-year-old female is admitted to the hospital with enterococcus endocarditis and is treated with penicillin and gentamicin. During her admission, she develops worsening pulmonary edema secondary to valvular insufficiency and requires therapy with IV furosemide. This patient is most likely to experience which of the following adverse reactions to her current pharmacological treatment: Review Topic

QID: 101034
1

Ringing in the ears and impaired hearing

81%

(17/21)

2

Hyperkalemia leading to possible cardiac arrhythmia

5%

(1/21)

3

Anemia and chronic fatigue

5%

(1/21)

4

Diffuse flushing and redness over body surface

5%

(1/21)

5

Pseudomembranous colitis and diarrhea

0%

(0/21)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.RL.16) An 82-year-old male with osteoarthritis, hypertension and allergic rhinitis was diagnosed 3 months ago with congestive heart failure and resultant pulmonary edema. Until recently, the patient's symptoms had been well controlled by furosemide therapy. Since beginning a new medication for a comorbid condition, he is more short of breath. A chest radiograph of the patient is shown in Figure A. Which of the following medications is likely responsible for these worsening symptoms? Review Topic

QID: 100970
FIGURES:
1

Spironolactone

13%

(14/106)

2

Naproxen

53%

(56/106)

3

Zileuton

8%

(8/106)

4

Montelukast

8%

(9/106)

5

Hydrochlorothiazide

14%

(15/106)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2
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Topic COMMENTS (7)
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