Osmotic Diuretics
Osmotic diuretics owe their
effects to the physical re-tention of fluid within the nephron rather than to
direct action on cellular sodium transport. These compounds are not
electrolytes, and they are freely filtered at the glomerulus and not reabsorbed
to a significant extent. Ideally, these drugs should be water-soluble
com-pounds, well absorbed after oral administration, freely filtered at the
glomerulus, poorly reabsorbed by the tubule, and devoid of pharmacological
effects. The pro-totype is mannitol (Osmitrol),
an unmetabolizable poly-saccharide derivative of sucrose. Other clinically
avail-able osmotic diuretics include glycerin (Glycerol, Osmoglyn, and
the topical agent Ophthalgan),
isosor-bide (Ismotic), and urea (Ureaphil, Urevert). Since these osmotic
agents act in part to retard tubule fluid reab-sorption, the amount of diuresis produced is propor-tional to the quantity of
osmotic diuretic administered. Therefore, unless large quantities of a
particular os-motic diuretic are given, the increase in urinary volume will not
be marked.
Ideally, the distribution of
osmotic diuretics should be largely confined to the vascular system, although
this can lead to excessive expansion of the vascular com-partment. Such an
overexpansion could precipitate pul-monary edema or increase cardiac work or
both. This is largely the result of rapid transfer of fluid from the in-terstitial
to the vascular compartment. Practically speaking, however, few osmotic
diuretics are available for therapeutic use. These agents, therefore, should be given cautiously to patients with compromised cardiac function.
The renal response to osmotic
diuretics is probably due to the interplay of several factors. The primary
effect in-volves an increased fluid loss
caused by the osmotically active diuretic molecules; this results in reduced NA+
and water reabsorption from the proximal tubule.
An additional contributing
factor to the diuresis in-duced by osmotic diuretics is the increase in renal medullary blood flow that follows their administration. This medullary hyperemia reduces the
cortex– medullary osmolar gradient by carrying away intersti-tial NA+
and urea. This partial reduction of the osmolar gradient impairs normal
reabsorption of tubular water, which occurs from the descending limb of Henle
and the collecting duct.
Finally, there is an
additional increase in electrolyte excretion due to impairment of ascending
limb and dis-tal tubule NA+ reabsorption; this occurs as a result of
lowered tubular NA+ concentration and the increased tubular fluid
flow rate.
Mannitol (Osmitrol) is a six-carbon sugar that
does not undergo appreciable metabolic degradation. It is not absorbed from the
gastrointestinal tract and there- fore must be given intravenously. Humans do
not reab-sorb it in the proximal tubules.
Mannitol is particularly
useful in clinical conditions characterized by hypotension and decreased
glomeru-lar filtration. These symptoms are usually the result of some physical
trauma or surgical procedure. Mannitol is useful in maintaining kidney function
in these condi-tions, since even at reduced rates of filtration, a suffi-cient
amount of the sugar may enter the tubular fluid to exert an osmotic effect and
thus continue urine forma-tion. However, if circulatory failure is profound and
glomerular filtration is severely compromised or absent, not enough mannitol
may reach the tubules to be effec-tive. The ability to maintain urine flow when
renal shut-down might otherwise be expected aids in preventing kidney tubular
damage. In addition, mannitol has been used to reduce cerebral edema during
neurosurgery, to reduce intraocular pressure before surgery for glau-coma, and
to promote the elimination of ingested toxic substances.
The major characteristics of
the renal response to mannitol diuresis include a fall in urine osmolality and
a decrease in the osmolality of the interstitial fluid of the renal medulla. The quantity of urine formation and NA+
excretion is generally proportional to
the amount of mannitol excreted. Although there is a significant
inhibi-tion of proximal water reabsorption, the effects of man-nitol on
proximal NA+ reabsorption are not marked.
The major adverse reactions
associated with manni-tol administration are headache, nausea, vomiting, chest
pain, and hyponatremia. Too rapid an administration of large amounts may cause
an excessive shift of fluid from the intracellular to the extracellular
compartment and result in congestive heart failure.
The primary use of anhydrous
glycerin (Ophthalgan) is as an
osmotic agent that is applied topically to reduce corneal edema. Orally administered
glycerin (Glycerol, Osmoglyn) is used to reduce intraocular
pressure and vitreous volume before
ocular surgery.
The use of urea (Ureaphil, Urevert) has declined in
recent years owing both to its disagreeable taste and to the increasing use of
mannitol for the same purposes. When used to reduce cerebrospinal fluid
pressure, urea is generally given by intravenous drip. Because of its
po-tential to expand the extracellular fluid volume, urea is contraindicated in
patients with severe impairment of renal, hepatic, or cardiac function or
active intracranial bleeding.
Isosorbide (Ismotic) is an orally effective,
osmoti-cally active drug that is most commonly used for theemergency treatment
of acute angle-closure glaucoma. It should not be confused with isosorbide
dinitrate, an antianginal drug.
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