Osmotic Diuretics
Medical Mnemonic for Osmotic diuretics:
GUM:: Glycerol Urea Mannitol
In discussing the specific drugs, we are going to “travel” along the nephron,
from the glomerulus to the collecting duct, “stopping” at sites where specific diuretics act.
OSMOTIC DIURETICS: include drugs such as mannitol (urea, glycerin, isosorbide)
Mannitol is pharmacologically inert & being freely filtered at Bowman’s capsule by the glomerulus & not reabsorbed
1. Chemical and pharmacokinetic properties of mannitol:
- small water-soluble molecule: a sugar alcohol with 6 C atoms and 6 OH groups
- pharmacologically inert so it can be given in large doses
- not readily permeable across the cell membrane therefore, mannitol is
– not absorbed orally (it is an osmotic laxative; >20g per os) given in i.v. infusion
– distributed in the extracellular space
– after being freely filtered in the renal glomeruli>> not reabsorbed in the tubules
2. Mechanisms of action of osmotic diuretics >> two-fold:
(1) After getting into the bloodstream and then into the extracellular water space,
osmotic diuretics cause increase in the osmolality of the plasma and the extracellular (EC) water .
>>osmotically extract(absorb) water from the intracellular space
>> causing expand/increase in the extracellular fluid volume
>> increase the renal blood flow, i. e.:
>>increase the glomerular blood flow>> increase GFR
>> increase the blood flow in vasa recta
>> NaCl in the interstitium of the medulla (carried there by Na+K+2Cl- symporter
of the ascending limb of the loop of Henle) will be washed out
>> decrease the medullary tonicity created by the ascending limb of the loop of Henle
>> decrease water reabsorption from the leaky descending limb of the loop of Henle
>> DIURESIS
(2) After being filtered in the glomeruli without being reabsorbed in the renal tubules, they
>> increase in the osmolality of the tubular fluid
>> decrease the reabsorption of water from the “leaky” segments of the tubular system, i.e. prevent passive re-absorption of H2O rather than Na+ excretion
>> from the proximal convoluted tubule, i.e.:
>> from the descending limb of the loop of Henle
>> from the collecting duct >> DIURESIS
So, Osmotic diuretic effect >> depend on the development of osmotic pressure.
