Medical Pharmacology Chapter 26:  Renal Pharmacology

Mechanisms whereby furosemide and thiazides are useful in calcium metabolism disorders management

• Role of Diuretics in Calcium Metabolism

  • Loop Diuretics and Calcium Metabolism

    • Furosemide (Lasix)

    • Torsemide (Demadex)

    • Bumetanide (Bumex)

  • Mechanism of action:

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

      • Inhibit the Na⁺/K⁺/2Cl^- transport system in the luminal membrane

        1. Reduction in sodium chloride reabsorption

        2. decreases 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.

           • 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.

      • Clinical Uses:

        •  Major uses:

          • Acute pulmonary edema

          • Acute hypercalcemia

          • Management of edema

• Thiazides and Calcium Metabolism

  • Mechanism of action:

    • Diuretic action:Inhibition of NaCl reabsorption from the distal convoluted tubule (luminal side)

    • Enhanced calcium reabsorption in the distal convoluted tubule (unknown mechanism)

      •  Thiazides infrequently cause hypercalcemia but can unmask hypercalcemia due to other causes such as carcinoma, sarcoidosis, or hyperparathyroidism.