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Osmotic diuretics

Related terms

Diuretics, Excretion, AVP, Interstitial fluid, Apical membrane, Loop diuretics, Potassium, Hyperosmotic, Osmotic pressure,
Thiazide diuretics

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Use of Diuretics in the Newborn Diuretic Use in Edema and the Prob
Jean-Pierre Guignard, in Nephrology and Fluid/Electrolyte
Resistance
Physiology: Neonatology Questions and Controversies (Second
David H. Ellison, Christopher S. Wilcox, in Therapy in Nep
Edition), 2012.
Hypertension (Third Edition), 2008.

Osmotic Diuretics Osmotic Diuretics

Osmotic diuretics are agents that inhibit the reabsorption of solute
Osmotic diuretics, such as mannitol, do not interfere dire
and water by altering osmotic driving forces along the nephron.
specific transport proteins but rather act as osmotic partic
tubule fluid. This inhibits both fluid and NaCl reabsorptio
Chemistry
details, please see Ellison and Wilcox,2 Better and colleagu
Warren and Blantz29). Thus, these drugs increase the
Mannitol, a hexahydric alcohol related to mannose with a molecular
only of fluid but also of Na+, K+, Cl, bicarbonate, and oth
weight of 182 d, is the main representative of this class of agents.18
The urinary osmolality during osmotic diuresis approache
plasma, regardless of the state of hydration. Osmotic
Mechanisms and Sites of Action
increase renal blood flow and wash out the medullary solu
Freely filtered and (mostly) not reabsorbed, osmotic diuretics increase gradient, effects that contribute to the diuretic-induced im
the tubular fluid osmolality, thus impairing the diffusion of water out in urinary concentrating capacity.
of the tubular lumen, as well as that of NaCl by a solvent drag effect.
The osmotic diuretics act in the proximal tubule and in the loop of Read full chapter
Henle. By attracting water from the intracellular compartment,
osmotic diuretics increase ECF volume and renal blood flow.
Increased medullary blood flow washes out the hypertonic medulla,
thus impairing the concentrating mechanism. By inhibiting NaCl
reabsorption out of the water-impermeable thick ascending limb,
osmotic diuretics also impair the dilution of urine. Osmotic diuretics Physiology of Diuretic Action
increase nonspecifically the excretion of all electrolytes. The
natriuresis induced by osmotic diuretics is only about 10% of the Bruce M. Koeppen Bruce A. Stanton, in Renal Physiology
filtered load. Edition), 2013.

Efficacy and Therapeutic Uses Sites of Action of Diuretics

Osmotic diuretics increase the excretion of Na+, K+, Cl, Mg++, Figure 10-1 depicts the nephron sites at which the differen
diuretics act. The osmotic diuretics act along the proximal

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Read full chapter
Kidney Function
DELMAR R. FINCO, in Clinical Biochemistry of Domestic Animals
(Third Edition), 1980.
Osmotic Diuretics
Osmotic diuretics are materials that are freely filtered by the
glomeruli but are not reabsorbed significantly or at all by the tubules.
A high intraluminal concentration is achieved as some water is
reabsorbed. However, the osmotic activity in the lumen interferes
with the normal passive reabsorption of water so that increased urine
volume occurs. During hyperglycemia glucose acts as an osmotic
diuretic because TG is exceeded. Mannitol, a nonmetabolizable sugar
alcohol, acts as an osmotic diuretic since it is freely filtered but totally
nonreabsorbable. Although the mechanisms are not known, osmotic
diuretics increase RBF and GFR moderately. They also decrease the
tubular reabsorption of sodium. This occurs as a consequence of a
decrease in sodium concentration of proximal tubule fluid brought
about by retention of water secondary to the osmotic agent. With the
decrease in sodium concentration, there is less of a gradient for
passive absorption into the cell of the tubule (Gennari and Kassirer,
1974). The greater flow of fluid to the more distal tubule prevents
adequate reabsorption of sodium, urea, and other components of the
fluid. As a consequence, urinary excretion of sodium, potassium,
calcium, phosphorus, magnesium, and urea is increased during both
acute and chronic osmotic diuresis (Gennari and Kassirer, 1974).
Concentration of urine depends on passive movement of water
secondary to osmotic gradients between the interstitium and the
distal tubule or collecting duct. Since osmotically active particles
remain in the tubular lumen, the presence of ADH and medullary
hypertonicity have no effect on the rate of urine flow during osmotic
diuresis. However, medullary blood flow rate increases and interstitial
sodium and urea levels decrease during osmotic diuresis in dogs
(Velasquez
Read full chapter
Diuretics
in Pocket Companion to Brenner and Rector's The Kidney (Eighth
Edition), 2011.
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portions of the thin descending limb of Henles loop (i.e.,
portions of the nephron that have a high water permeabili
carbonic anhydrase inhibitors act primarily in the proxima
The thick ascending limb of Henles loop is the site of acti
loop diuretics. The early portion of the distal tubule is the
action of the thiazide diuretics, and the K+-sparing
primarily on the late portion of the distal tubule and the
portion of the collecting duct where they not only inhibit N
reabsorption but also K+ secretion. This same class of
can inhibit Na+ reabsorption in portions of the collecting
not secrete K+.
The site of action of a diuretic in turn determines the mag
the associated natriuresis (Table 10-1). For example,
on the thick ascending limb of Henles loop cause a larger
than diuretics acting on the early portion of the distal tubu
a larger portion of the filtered Na+ is absorbed by the thick
limb (see ). The effect diuretics have on the handling of so
than Na+ also depends on the site of action. Examples illu
this point are given in subsequent sections.
Mechanisms of Action of Diuretics
Osmotic Diuretics
Osmotic diuretics, as the name implies, are agents that in
FIGURE 10-1
Sites of action of diuretics
and aquaretics along the
nephron. CCD, Cortical
collecting duct; DT, distal
Read full chapter
Disorders of Extracellular Volume
Elwaleed A. Elhassan, Robert W. Schrier, in Comprehensiv
Nephrology (Fourth Edition), 2010.
Osmotic Diuretics
Osmotic diuretics are substances that are freely filtered at
glomerulus but are poorly reabsorbed. Mannitol is the pro
these diuretics. The mechanism by which mannitol produ
is that it increases the osmotic pressure within the lumen
proximal tubule and the loop of Henle. This causes enhan
diuresis and, to a lesser extent, sodium and potassium
Patients with reduced cardiac output may develop pulmon
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Osmotic Diuretics when given mannitol because of an initial intravascular

Site of Action
Osmotic diuretics do not act on any specific transport pathway. They
act as osmotic particles in tubule fluid and are freely filtered but
poorly reabsorbed.
Mechanism of Action
Filtered mannitol is concentrated sufficiently to diminish tubular
fluid reabsorption. Ongoing Na+ reabsorption creates an osmotic
gradient for back-flux of reabsorbed Na+ into the tubule. Increased
distal flow stimulates K+ secretion. Mannitol increases the total renal
and medullary blood flow and decreases the medullary solute
gradient, preventing urinary concentration.
Pharmacokinetics and Dosage
Mannitol is distributed in the ECV and is filtered freely at the
glomerulus. Consequently, the t for plasma clearance depends on the
GFR and can be prolonged up to 36 hours in advanced kidney
disease. It can be infused intravenously in daily doses of 50 to 200 g
as a 15% or 20% solution or 1.5 to 2 g/kg of 20% mannitol over 30 to
60 minutes to treat raised intraocular or intracranial pressure.
Clinical Indications
Mannitol is used in the management of severe head injury, where it
is more effective than loop diuretics or hypertonic saline in reducing
brain water content, and has been used with success i
Read full chapter
phase. Therefore, mannitol is not a preferred agent for tre
edematous states but is rather used to treat cerebral edem
by trauma or neoplasms and to reduce intraocular pressur
use for mannitol is in the treatment of dialysis disequilibri
syndrome, whereby it increases the serum osmolality and
decreases the rapid rate of solute removal by dialysis, whic
thought to be responsible for the symptoms of the syndro
Read full chapter
Physiology and Pathophysiology of
Diuretic Action
David H. Ellison, in Seldin and Giebisch's The Kidney (Fift
2013.
Osmotic Diuretics
Osmotic diuretics are substances that are freely filtered at
glomerulus, but are poorly reabsorbed (see Figure 40.2). T
pharmacological activity of drugs in this group depends e
the osmotic pressure exerted by the drug molecules in sol
not on interaction with specific transport proteins or
Mannitol is the prototypical osmotic diuretic. Its diuretic e
due to interactions with receptors or renal transporters, bu
is due to more complex mechanisms that involve osmotic
tubule epithelium and reduction of the medullary interstit
osmolality. Because the relationship between the magnitu
and concentration of osmotic diuretic in solution is linear
used clinically are small molecules. Other agents consider
class include urea, sorbitol, and glycerol.

Regulation of K+ Excretion Urinary Electrolyte Excretion

Although osmotic agents do not act directly on transport p
Gerhard Malnic, Gerhard Giebisch, Shigeaki Muto, Wenhui Wang,
the rate of transport of ions is affected. Following the infu
Matthew A. Bailey, Lisa M. Satlin, in Seldin and Giebisch's The Kidney
mannitol, the excretion of sodium, potassium, calcium
(Fifth Edition), 2013.
bicarbonate, and chloride is increased (see Table 40.1). Th
reabsorption rates for sodium and water are reduced subs
Diuretics following the infusion of mannitol. Reabsorption of magn
calcium are also reduced in the proximal tubule and loop
Diuretic drugs, used primarily to promote excretion of salt and water,
and phosphate reabsorption is inhibited slightly along the
also affect renal K+ excretion.73,134,135,171,181,186,201,234,345,524
tubule. In addition to increasing electrolyte excretion
Figure 49.45 illustrates the primary renal sites of action of
infusion increases cortical and medullary blood flow, and
compounds representative of three classes of diuretic drugs that act
variable effect on GFR. The most pronounced effect obser
from the luminal side of tubule cells. Loop diuretics, such as
mannitol is a brisk diuresis and natriuresis.
furosemide, act mainly on the Na-K-2Cl co-transporter in the apical
membrane of thick ascending limb cells.7476,198,201,234 Thiazide
diuretics have their primary action on an Na-Cl co-transporter in cells
of the distal convoluted tubule.95,234,522524 Loop and thiazide
diuretics are both capable of increasing K+ excretion. K+-sparing
diuretics, exemplified by amiloride and triamterene, block Na
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channels in principal cells of the ICT and CCD.19,73,119,232,357 Renal Figure 40.2
Structures of osmotic
K+ excretion depends primarily on secretion by principal cells in the diuretics.

ICT and CCD. Amiloride targets these cells by a blocking ENaC,

reducing the transepithelial potential difference and diminishing the Read full chapter
driving focrce for K+ secretion. Luminal Ca2+ also blocks ENaC, and
has similar inhibitory effects on K+ secretion.372

Loop diuretics increase renal K+ excretion, in part by direct effects on

TAL cells, and also by secondary effects on principal cells in the ICT
and CCD. Thus, furosemide inhibition of the Na-K-2Cl co-
transporter leaves the cell-to-lumen K+ flux through apical
membrane channels unopposed, resulting in either greatly reduced Renal Pharmacology
K+ absorption or even reversal to produce net K+ secretion, along the
TAL.201,511,512 The inhibition of Na and Cl absorption in the TAL also E.K. Jackson, in Reference Module in Biomedical Sciences
reduces medullary interstitial osmolality and results in decreased
fluid absorption along the descending limb. Thus, loop diuretics not Osmotic Diuretics (Examples: Mannitol, Glycerin
only decrease K+ rea Isosorbide, Urea)

Osmotic diuretics are relatively inert substances; they do n

Figure 49.45
Distribution of NKCC2,
ROMK, the CIC--sub-
unit Barttin, CIC-Kb, and
NCCT along the nephron
Read full chapter
Diuretics
Gary O. Rankin, in xPharm: The Comprehensive Pharmacology
Reference, 2007.
Contraindications
Osmotic diuretics are contraindicated in anuric patients and patients
not responding to test doses. Mannitol and urea should not be used
in patients with active cranial bleeding. Carbonic anhydrase
inhibitors, thiazides and sulfonamide-based loop diuretics are
contraindicated in patients allergic to sulfonamides. Carbonic
anhydrase inhibitors are contraindicated in patients with
hyperchloremic acidosis or severe chronic obstructive pulmonary
disease. Loop diuretics are also contraindicated in patients with
severe sodium and volume depletion and anuric patients or patients
not responsive to a test dose. Potassium sparing diuretics are
contraindicated in patients with hyperkalemia or who are at risk of
developing hyperkalemia.
interact with renal transport systems. Instead, osmotic diu
filtered into the renal tubules, undergo minimal reabsorpt
accomplish diuresis in part due to their physical presence
tubular lumen. In this regard, because osmotic diuretics
not reabsorbed, their presence in the tubular lumen limits
osmosis of water into the interstitial space. This results in
the luminal electrolyte concentrations to the point that the
reabsorption of electrolytes is reduced. Because osmotic d
have limited cellular permeability, their presence in the bl
osmotic extraction of water from cells; a process that expa
extracellular fluid volume, decreases blood viscosity, inhib
release, and increases renal blood flow. Probably these cha
contribute to the ability of osmotic diuretics to cause diure
Osmotic diuretics act both in the PT and loop of Henle, w
of Henle probably being the main site of action; and they
urinary excretion of most electrolytes, including Na
Cl, HCO, and phosphate. Although osmotic diuretics
their osmotic properties can induce serious adverse effect
example, expansion of the extracellular fluid volume by
diuretics may cause heart failure, pulmonary congestion
pulmonary edema. Also dilution of the plasma may result
hyponatremia leading to headache, nausea, and vomiting
of water in excess of sodium can cause hypernatremia and
dehydration. Osmotic diuretics have several important use
treatment of dialysis disequilibrium syndrome, reducing
pressure, and managing cerebral edema.
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