OSMOTIC DIURETICS

Osmotic diuretics:
is a type of diuretic that inhibits
reabsorption of H
2
0 and Na
+
.

Pharmacologically inert
substances intravenously.

osmolarity of blood and
renal filtrate.

Properties of Osmotic Diuretics
It is freely filtered at the glomerulus.
It undergoes minimal reabsorption.
It is not metabolized to a significant
degree.
It is pharmacologically inert (ie, it has
no direct effects on the biochemistry
or physiology of cells).

Osmotic diuretics:
H
2
0 retention:
proximal tubule
descending limb of loop of Henle (freely permeable to
water)

Small enough molecules ultrafiltration barrier
nephron
OD mol. :
block the reabsorption of solutes from the nephron
(especially Na)
Or
are not easily absorbed from the nephron themselves;
large enough not to pass through PT & DLLH (mannitol).

filtrate(solutes)filtrate :
exert an osmotic effect that inhibits the reabsorption of
water.

Sites of Action:
Descending Loop of Henle:
major site of action
Osmosis; H
2
0conc. bet. interstitium vs.
tubular fluid

Proximal tubule
Osmosis; same as DLH

Collecting duct
oppose ADH
Nephron sites of action of diuretics
Therapeutic Uses:
Acute or incipient renal failure
Acute attacks of glaucoma
Reduce preoperative intraocular
pressure (alter Starling forces; IaCV)
Reduce pre-surgical or post-
trauma intracranial pressure
(cerebral edema)
Prompt removal of renal toxins



EFFECTS ON URINARY
EXCRETION
Osmotic diuretics increase the urinary
excretion of nearly all electrolytes,
including:
Na
+
K
+
Ca
2
+
Mg
2
+
Cl

HCO
3

H
2
PO
4


EFFECTS ON RENAL
HEMODYNAMICS
renal blood flow (RBF)

Little to no change in the glomerular
filtration rate (GFR)

Toxicity/Adverse effects:
Dehydration
Hyponatremia ( urine FR, contact bet. fluid &
tub. cells, Na+ reabsorption)
Headache
Nausea
Vomiting
Hypernatremia (H20 diuresis > naturesis)
Tachycardia
Acidosis (prox. Tube. exc. of acids)
Edema (all caps. Permeable; expt. brain)
Fluid and Electrolyte Imbalance


CONTRAINDICATIONS
Generally, contraindicated in patients
with:
heart failure or pulmonary congestion
frank pulmonary edema ( extracellular
volume and hyponatremia; perm. caps.)
patients who are anuric owing to renal
disease
patients who are unresponsive to test
doses of the drugs
EXAMPLES OF OSMOTIC
DIURETICS

MANNITOL (OSMITROL)
Is a simple six-carbon sugar
that possesses the four
properties characteristic of an
osmotic diuretic

Of the four, is the only one
used for its diuretic actions



Mechanism of Diuretic Action
Promotes diuresis by creating an osmotic
force within the lumen of the nephron.

concentration of mannitol in the filtrate,
degree of diuresis; the more mannitol
present, the greater the diuresis.
No significant effect on the excretion of K
+

and other electrolytes
Filtration (of OD mols. in nephron)

Minimal Reabsorption

Remains w/n nephron

Osmotic force

X passive RA of H20

Urine Output



Pharmacokinetics
X diffuse across the GI epithelium and
cannot be transported by the uptake
systems that absorb dietary sugars.
parenterally
Following IV injection, mannitol
distributes freely to extracellular water.
Onset: 30 to 60 minutes
Duration: 6 to 8 hours.
Excretion: Mostly intact in urine
Therapeutic Uses
Prophylaxis of Renal Failure
X shut down of kidney; osmosis

Reduction of Intracranial Pressure

Reduction of Intraocular Pressure
Acute angle-closure glaucoma
STAT
Open angle Glaucoma
Perioperative period


Therapeutic Uses
To treat drug intoxication

Adverse Effects
Thrombophlebitis
Convulsions
Edema (CHF, Pulmonary)
Headache
Nausea
Vomiting
Fluid and electrolyte imbalance
CONTRAINDICATIONS
Mannitol
Drug allergy
Severe renal disease
Pulmonary Edema
Patients with active intracranial bleeding
(free mannitol mols.in ECF; CE)

Drug Interactions
None
Preparations, Dosage, and
Administration
Administered by IV infusion
Test dose of mannitol (12.5 g
intravenously)
Solutions for IV use: 5%-25%.
Dosing depends on objective of therapy
(prevention of renal failure, lowering of ICP,
lowering of IOP)
The usual adult dosage for preventing
renal failure: 50 -100 gm /24 hours.
The infusion rate should be set to elicit a
urine flow of at least 30 to 50 mL/hr.

Low temperature: may crystallize
(>15%).
Observed for crystals prior to use.
Preparations that contain crystals
should be warmed (to redissolve the
mannitol) and then cooled to body
temperature for administration.
A filter needle: vial
In-line filter: prevent crystals from
entering the circulation.
Urea, Glycerin, and Isosorbide
These agents are freely filtered at the
glomerulus and undergo limited
reabsorption which promotes osmotic
diuresis.
Are not used for osmotic diuresis.
They are used only to reduce IOP and
ICP
CONTRAINDICATIONS
Urea
may cause thrombosis or pain if
extravasation occurs
patients with impaired liver function
risk of blood ammonia levels

patients with active intracranial bleeding

CONTRAINDICATIONS

Glycerin
Hyperglycemia (metabolised)