II. Indications

  1. Symptomatically reduce pulmonary and Peripheral Edema
    1. Congestive Heart Failure
    2. Nephrotic Syndrome
    3. Renal Insufficiency (GFR<30%)
      1. Other Diuretics (e.g. Thiazide Diuretics) are ineffective at low GFR
      2. Loop Diuretics (esp. Furosemide) may be used to prevent weight gain between Dialysis runs
  2. Emergency Management of Pulmonary Congestion (Lasix)
    1. Left Ventricular Dysfunction (CHF)

III. Contraindications

IV. Precautions

  1. All Loop Diuretics except Torsemide need to be dosed twice daily for effect
  2. Loop Diuretics are associated with significant Electrolyte abnormalities and volume depletion (FDA black box warning)
  3. Loop Diuretics have a threshold dose, below which they have no effect
  4. Loop Diuretics have a ceiling dose, above which increasing dose has little effect
    1. Better in these cases to increase frequency at the ceiling dose

V. Mechanism

  1. Loop Diuretics are the most potent of Diuretics
  2. Loop Diuretic potently inhibits reabsorption of Sodium and chloride
    1. nephron.png
    2. Action at ascending loop of Henle in glomerulus (Inhibits Na+/K+/Cl+ co-transporter)
    3. Results in increased urinary Sodium and water excretion
    4. Also associated with Potassium wasting
  3. Direct Venodilation in Pulmonary Edema
    1. Reduces venous return (Preload)
    2. Reduces Central Venous Pressure
    3. Synergistic effect with Morphine and Nitroglycerin
  4. Reduces Intravascular Volume
    1. Reduces Cardiac Output
    2. Beware Hypotension in Myocardial Infarction

VII. Medications: Relative Potency (40 to 20 to 1)

  1. Furosemide (Lasix) 40 mg IV (equivalent to 80 mg oral, but variable Bioavailability)
  2. Torsemide (Demadex) 20 mg IV (equivalent to 20 mg oral)
  3. Bumetanide (Bumex) 1 mg IV (equivalent to 1 mg oral)
  4. References
    1. Pham (2017) Card Fail Rev 3(2):108-122 +PMID: 29387462 [PubMed]

VIII. Adverse Effects

  1. Risk of central volume depletion (Dehydration, Hypotension and contraction alkalosis)
  2. Renal dysfunction
    1. Minimize dosage when starting an ACE Inhibitor
    2. Avoid NSAIDs
  3. Hypersensitivity (esp. Sulfonamide)
    1. Ethacrynic Acid is the only non-sulfonamide Loop Diuretic
  4. Electrolyte abnormalities
    1. Hypokalemia
    2. Hypomagnesemia
    3. Metabolic Alkalosis
    4. Hyperosmolality
    5. Hyponatremia
      1. Hyponatremia is less common with Loop Diuretics than with Thiazide Diuretics
    6. Hypocalcemia
      1. Loop Diuretics increase Calcium excretion
      2. Contrast with Thiazide Diuretics which decrease Calcium excretion
  5. Ototoxocity
    1. Typically reversible (but permanent Deafness may occur)
    2. Risk Factors
      1. Higher Loop Diuretic serum concentrations (esp. high dose Furosemide)
      2. Renal dysfunction
      3. Concurrent Aminoglycoside use
      4. More common with Ethacrynic Acid

IX. Mechanism: Loop Diuretic Resistance

  1. Renal Insufficiency
    1. Renal Toxin (e.g. NSAID) decreases GFR
    2. NSAIDs
  2. Decreased Diuretic oral absorption
  3. Structural changes in the Kidney
    1. Normal aging
    2. Distal tubular hypertrophy (long term use)
      1. Consider adding a Thiazide Diuretic
      2. Counters distal tubular reabsorption
      3. Significantly boosts Loop Diuretic effect
  4. Increased Dietary Sodium intake
    1. CHF patient is an avid Sodium retainer
    2. Sodium is common in most foods
      1. See Dietary Sodium

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