Nursing Pharmacology Chapter 26:  Renal Pharmacology

Loop Diuretic Drugs

• Introduction

  • Agents include:

    • Furosemide (Lasix)

    • Bumetanide (Bumex)

    • Torsemide (Demadex)

    • Ethycrinic acid

• Mechanism of action

  • Inhibition of NaCl reabsorption in the thick ascending limb of the loop of Henle

    • Loop diuretics inhibit the Na⁺/K⁺/2Cl^- transport system in the luminal membrane resulting in:

      1.  Reduction in sodium chloride reabsorption.

      2.  A decrease in the normal lumen-positive potential (secondary to potassium recycling)

      3.  A positive lumen potential: drives divalent cationic reabsorption (calcium magnesium)

      4.  As a consequence, loop diuretics increase magnesium and calcium excretion.

         • Hypomagnesemia may occur in some patients.

         • Hypocalcemia does not usually develop because calcium is reabsorbed in the distal convoluted tubule.

           • In circumstances that result in hypercalcemia, calcium excretion can be enhanced by administration of loop diuretics with saline infusion.

  • Since a significant percentage of filtered NaCl is absorbed by the thick ascending limb of loop of Henle, diuretics acting at this site are highly effective

• Loop diuretics:  Properties:  

  • These agents are rapidly absorbed following oral administration (may be administered by IV).

    • Rapid onset of action

      • Eliminated by a renal secretion and glomerular filtration with a half-life dependent on kidney function.

    • Co-administration of drugs that inhibit weak acid secretion such as probenecid or indomethacin may alter loop diuretic clearance.

    • Other effects:

      • Furosemide: increases renal blood flow; blood flow redistribution within the renal cortex

      • Furosemide decreases pulmonary congestion and the left ventricular filling pressure in congestive heart failure (CHF) -- prior to an increase in urine output.

• Clinical Uses

  • Major uses include:

    • Acute pulmonary edema

    • Acute hypercalcemia

    • Management of edema

  • Other uses:

    • Hyperkalemia

      • Loop diuretics increase potassium excretion

      • This effect is increased by concurrent administration of NaCl and water.

    • Acute renal failure

      • May increase rate of urine flow and increase potassium excretion.

      • May convert oligouric to non-oligouric failure {easier clinical management}

      • Renal failure duration -- not affected

    •  Anion overload

      • Bromide, chloride, iodide: all reabsorbed by the thick ascending loop:

      • Systemic toxicity may be reduced by decreasing reabsorption

        • concurrent administration of sodium chloride and fluid is required to prevent volume depletion

•  Toxicity

  •  Hypokalemia metabolic alkalosis

    • Increased delivery of NaCl and water to the collecting duct increases potassium and proton secretion-- causing a hypokalemic metabolic alkalosis

    • In managed by potassium replacement and by ensuring adequate fluid intake

  • Ototoxicity

    • Dose-related hearing loss (in usually reversible)

    • Ototoxicity more common:

      •  With decreased renal function

      •  With concurrent administration of other ototoxic drugs such as aminoglycosides

  •  Hyperuricemia

    • May cause gout

    • Loop diuretics cause increased uric acid reabsorption in the proximal tubule, secondary to hypovolemic states.

  •  Hypomagnesemia: loop diuretics cause

    1. Reduction in sodium chloride reabsorption

    2. Decreases in normal lumen-positive potential (secondary to potassium recycling)

    3. Positive lumen potential: drives divalent cationic reabsorption (calcium magnesium)

    4. Therefore, loop diuretics increase magnesium and calcium excretion.

       • Hypomagnesemia may occur in some patients.

       • Reversed by oral magnesium administration

  •  Allergic reactions

    • Furosemide: skin rash, eosinophilia, interstitial nephritis(less often)

  • Other toxicities

    • Dehydration which may be severe

    • Hyponatremia which is less common than with thiazides but may occur in patients who increased water intake in response to a hypovolemic thirst.

    • Hypercalcemia may occur in severe dehydration and if a hypercalcemia condition {e.g. oat cell long carcinoma} is also present.

Ives, H.E., Diuretic Agents, in: Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 242-259.

Jackson, E.K. Diuretics In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp. 685- 713

Jackson, E.K. Vasopressin and Other Agents Affecting the Renal Conservation of Water In, Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.715-732