Anesthesia Pharmacology:  Renal Pharmacology

• Osmotic Diuretics

  • Introduction:

    • Osmotic diuretics cause water to be retained within the proximal tubule and descending limb of loop of Henle (freely permeable to water)

    • Mannitol (Osmitrol) is an example of osmotic diuretic.

    • Clinical Use: mainly used to reduce increased intracranial pressure;

  • Osmotic diuretics: properties

    • Mannitol (Osmitrol) : not metabolized, freely filtered at the glomerular

    • Usually administered by IV; oral administration results in an osmotic diarrhea-- perhaps useful to promote elimination of toxic substances from the GI tract (in conjunction with activated charcoal)

    • Urine volume increases with mannitol excretion due to direct osmotic effects

      • Sodium reabsorption is reduced because of increased urine flow rates {decreased contact time between urine and tubular epithelial cells}

  • Clinical Uses:

    • To increase urine volume:

      • May be used to prevent anuria if the kidney due to hemolysis or rhabdomyolysis is presented with a large pigmented load.

      • When renal hemodynamics are compromised

    • To decrease intracranial or intraocular pressure:

      • Mannitol (Osmitrol) extract water from intracellular compartments, reducing total body water

      • Following IV administration, intracranial pressure falls within 60-90 minutes.

  •  Toxicity:

    • Volume expansion effects:  increased extra cellular fluid volume and hyponatremia may cause:

      •  pulmonary edema, complicating congestive heart failure

    • Headache, nausea, vomiting (commonly observed)

    • Dehydration and hypernatremia:

      • Fluid loss leads to significant dehydration and in the absence of adequate fluid replacement leads to hypernatremia.

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