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OSMOTIC DIURETICS

OSMOTIC DIURETICS

ACTIONS AND MECHANISM

In the nephron, water reabsorption is a passive phenomenon that relies on the transcellular osmotic gradients established during the reabsorption of solutes, especially sodium. Osmotic diuretics alter these gradients to produce diuresis. After intravenous administration, such agents undergo filtration at the glomerulus but then cannot be reabsorbed. As sodium and water are reabsorbed, osmotic diuretics become more concentrated in the tubular lumen, eventually generating an osmotic gradient that interferes with further fluid reabsorption. In the proximal tubule, the decreased fluid reabsorption also establishes a transepithelial sodium concentration gradient, normally prevented by the iso-osmotic reabsorption of water, that limits further sodium reabsorption.

In the general circulation, osmotic agents are also restricted to the extracellular space. As a result, fluid shifts from the intracellular to extracellular space, expanding the extracellular volume. An increase in renal blood flow ensues, which is transmitted to the medullary microcirculation and causes solute wash-out from the interstitium. As a result, there is a reduced gradient for water reabsorption from the collecting duct, promoting further water losses.

 

OSMOTIC DIURETICS

COMMON AGENTS

The major osmotic diuretic is mannitol, which has a half-life of 0.25 to 1.7 hours and primarily undergoes renal excretion.

 

INDICATIONS

The most common indications for mannitol include:

·   Acute kidney injury, although several randomized con- trolled studies have found that mannitol offers no benefit in this setting.

·  Cerebral edema. Mannitol is restricted from the brain by the blood-brain barrier. Therefore, its presence in the general circulation produces an osmotic gradient that promotes a shift of free water from the cerebrospinal fluid to the blood.

·     Acute closed-angle glaucoma. For the reasons described, mannitol can promote fluid shifts from the eye into the general circulation.

 

ADVERSE EFFECTS

The major adverse effects of mannitol include:

·  Hyponatremia/hypernatremia. Osmotic agents are associated with an initial phase of hyponatremia, which results from the systemic efflux of intracellular fluid in response to extracellular hyperosmolality (“pseudohyponatremia”). As free water is excreted with mannitol in the urine, hypernatremia follows, which can cause mental status changes, headache, lethargy, and nausea.

·    Hyperkalemic acidosis. As water is drawn out of cells, the intracellular concentrations of potassium and protons can rise, prompting their efflux through membrane channels. Hyperkalemic acidosis may persist in patients with poor renal function, who cannot eliminate the excess extracellular potassium or protons.

·      Pulmonary edema owing to the expansion of extracellular volume