Osmotic diuretics, such as mannitol and isosorbide, work by increasing osmotic pressure in the renal tubules, leading to increased urine output and are used for conditions like acute renal failure, increased intracranial pressure, and acute glaucoma. They operate primarily in the proximal convoluted tubule and the loop of Henle, counteracting ADH and preventing water reabsorption, but can lead to side effects like dehydration and electrolyte imbalance. These agents effectively reduce cerebrospinal fluid volume and lower intracranial pressure while also aiding in toxin elimination.

1. Clinical
Pharmacology of
Osmotic Diuretics
By
Chimata Akash
GM20-098

2. Introduction
 Osmotic diuretics are medications that work by increasing
the osmotic pressure of the renal tubules, drawing water
into the tubules from surrounding tissues. This results in
increased urine output, which can be beneficial in various
clinical conditions.

3. Two examples
are Mannitol and Isosorbide.
 In the nephron, osmotic diuretics act at the portions of the
nephron that are water-permeable.
 Osmotic diuretics work by expanding extracellular fluid and
plasma volume, therefore increasing blood flow to
the kidney. This washes out the cortical medullary
gradient in the kidney. This stops the loop of Henle from
concentrating urine, which usually uses the high osmotic
and solute gradient to transport solutes and water.

4.  These agents can also act at other parts of the body. For
example, they can be used to reduce intracranial and intra-
ocular pressure. Osmotic diuretics increase plasma volume,
but because they do not cross the blood-brain barrier, this
does not affect the nervous system. In effect, this is the
cause of their action reducing locally the plasma volume in
the nervous system.

5. Mechanism
of action
 Osmotic diuretics have their major effect in the proximal
convoluted tubule and the descending limb of the Loop of
Henle. These sites are freely permeable to water. Through
osmotic effects, they also oppose the action of ADH in the
collecting tubule. The presence of a nonreabsorbable
solute such as mannitol prevents the normal absorption of
water by interposing a countervailing osmotic force. As a
result, urine volume increases.

6. Mechanism of action
 The increase in urine flow rate decreases the contact time
between fluid and the tubular epithelium, thus reducing
sodium as well as water reabsorption. The resulting
natriuresis is of lesser magnitude than the water diuresis,
leading eventually to excessive water loss and
hypernatremia.

7. Mechanism of action
 Any osmotically active agent that is filtered by the
glomerulus but not reabsorbed causes water to be retained
in these segments and promotes a water diuresis. Such
agents can be used to reduce intracranial pressure and to
promote prompt removal of renal toxins. The prototypical
osmotic diuretic is mannitol.

8. Mechanism of action
 Mannitol lowers the intra cranial pressure through two
effects in the brain. The first, rheological effect, reduces
blood viscosity, and promotes plasma expansion and
cerebral oxygen delivery. In response, cerebral
vasoconstriction occurs due to autoregulation, and cerebral
blood volume is decreased. The second effect occurs
through creation of an osmotic gradient across the blood-
brain barrier, leading to the movement of water from the
parenchyma to the intravascular space. Brain tissue volume
is decreased and, therefore, ICP is lowered

9. Clinical Uses
 Osmotic diuretics are used in several clinical situations, including:
• Acute Renal Failure: To promote urine output and prevent or
treat oliguria or anuria.
• Increased Intracranial Pressure: To reduce cerebral edema and
intracranial pressure in conditions like brain injury or cerebral
hemorrhage.
• Acute Glaucoma: To decrease intraocular pressure by reducing
aqueous humor production.
• Toxin Removal: In certain cases, osmotic diuretics can help
enhance the elimination of toxins from the body.

10. Side Effects
 While osmotic diuretics can be effective, they may also
cause some side effects, including:
• Dehydration: Excessive fluid loss can lead to dehydration.
• Electrolyte imbalance: Sodium, potassium, and other
electrolyte levels may become imbalanced.
• Headache: In some cases, osmotic diuretics can cause
headaches.
• Pulmonary edema: In rare cases, especially in patients
with heart failure, pulmonary edema can occur.