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Diuretics: Osmotic diuretics (indication (diuretic effect + α) (Prevention…
Diuretics: Osmotic diuretics
Chemical and pharmacokinetic properties of mannitol
small water soluble molecule
sugar alcohol with 6 C atoms and 6 OH groups
Inert compund
can be given in large doses
not permeable across the cell membrane, so mannitol is
not absorbed orally -> given i.v. infusion
distributed in the extracellular space
once filtrated in glomeruli, it is not reabsorbed in the tubule
MOA
Get into the blood stream and then into the extracellular water space
osmotic diuretics increase the osmolarity of the plasma and EC water -> extract water from the intracellular space -> extracellular volume↑
renal blood flow↑
GFR↑ & blood flow of vasa recta↑
NaCl in the interstitium of medulla is washed out (by Na+-K+-2Cl- symporter of ascending limb of LOP)
corticomedullary gradient↓
water reabsorption from the leaky descending limb of LOH↓
diuresis
Get into the renal tubule by filtration
There is no reabsorption of osmotic diuretics (mannitol)
reabsorption of water from the leaky segment of tubular system↓ (proximal convoluted tubule / descending limb of LOH / collecting duct)
diuresis
osmotic diuretics
water excretion -> salt excretion
dilution of tubular fluid (salt reabsorption↓)
faster tubular flow (salt reabsorption↓)
indication (diuretic effect + α)
Prevention of anuria in acute renal failure
the patient is already oligouric, a test dose of mannitol is given in infusion
if it produce diuresis -> continue
if it is ineffective -> stop, otherwise overexpansion of EC volume overloads heart, inducing pulmonary edema
in this case, furosemide is better
treatment of acute cerebral and glaucoma
osmotic diuretics extract water out of the brain and the eyes -> lower the intracranial and intraocular pressure
treatment of dialysis disequilibrium syndrome
aggressive hemodialysis removes solutes form the EC compartment -> water gets into cells -> water intoxication-like symptom (brain edema)
in this case, mannitol extract water from the cells
treatment of cystic fibrosis
by inhalation of dry power mannitol -> dilution of viscid bronchial fluid -> promoting mucociliary clearance
Side effect
overdose-induced overexpansion of EC fluid
increase load of the heart + pulmonary edema (so, mannitol must not used in pulmonary edema -> furosemide is better)
other osmotic diuretics
glycerin
Oral
metabolized in liver as well
T1/2 <1hr
not in diabetes (glycerin is gluconeogenetic)
Contraindications
all osmotic diuretics
not in anuria and heart failure -> expansion of EC fluid overloads heart
urea
not in cirrhosis -> at high concentration, urea may inhibit arginase and it impairs the elimination of NH3 in urea cycle
glycerin
not in diabetes -> glycerin is gluconeogenic substracte
mannitol and urea
not in intracranial bleeding -> infusion may cause intravascular volume, worsening bleeding