Contributors:Evan Debevec-McKenney, Ursula Florjanczyk, MScBMC, Samantha McBundy, MFA, CMI, Viviana Popa, MD
Diuretics are medications that act on the kidneys to increase production of urine, and therefore, elimination of water from the body.
There are 5 main types of diuretics: carbonic anhydrase inhibitors; loop diuretics; thiazide and thiazide-like diuretics; potassium sparing diuretics; and last but not least, osmotic diuretics - which we’ll get intimately acquainted with during this video.
Now, the basic unit of the kidney is called a nephron, and each nephron is made up of a glomerulus, which filters the blood. The filtered content goes through the renal tubule, where excess waste, and molecules (such as ions and water), are removed or filtered through an exchange between the tubule and the peritubular capillaries. So the renal tubule plays a huge role in secretion and reabsorption of fluid and ions - such as sodium, potassium, and chloride - in order to maintain homeostasis - or the the balance of fluid and ions in our body.
The renal tubule has a few segments of its own: the proximal convoluted tubule; the U-shaped loop of Henle, with a thin descending, a thin ascending, and a thick ascending limb; and finally, the distal convoluted tubule, which empties into the collecting duct, which collects the urine.
The prototypal osmotic diuretic is mannitol; other osmotic diuretics like glycerin and isosorbide are rarely used.
Following IV administration, mannitol travels through the bloodstream and acts like you’d expect an osmotically active molecule to act: it sucks water out of the cells it encounters along the way, and all that extra water reaches the kidneys as increased renal blood flow.
Once at the kidneys, it gets secreted by the glomerulus into the renal tubule. Some of the segments of the renal tubule, like the proximal convoluted tubule and the thin descending limb, are freely permeable to water. So any osmotic agent that ends up here will tend to make water stay inside the tubule, rather than be reabsorbed.
Now, this increased volume leads to increased flow rate through the nephron, so there’s less time for the sodium to be reabsorbed. This causes a small increase in sodium loss, but much more water is lost, so mannitol is considered an aquaretic diuretic, meaning it promotes water excretion without increasing the loss of electrolytes.
This can come in handy when we need to remove water from the body, but only in certain conditions. Unlike other diuretics which are often used to treat hypertension and edematous states, osmotic diuretics are mainly used to lower intraocular pressure in glaucoma and before ophthalmologic procedures; or to lower intracranial pressure, such as following head trauma.
Since mannitol also increases renal blood flow, it can be used to flush away harmful substances that builds up in the kidney. Examples include myoglobin from rhabdomyolysis, which is the break down of muscles, and hemoglobin from hemolysis, which is the breakdown of red blood cells.
Now for side effects, first off, right after mannitol enters the bloodstream and before it gets excreted, it pulls intracellular fluid into the extracellular space, so it could worsen edematous states like pulmonary edema. When more water gets pulled into the blood vessels, the concentration of sodium will go down, causing hyponatremia. This is especially likely to happen in individuals with renal impairment, where the kidneys can’t excrete the mannitol, and in congestive heart failure, where the heart can’t handle the increased plasma volume.
- "Katzung & Trevor's Pharmacology Examination and Board Review,12th Edition" McGraw-Hill Education / Medical (2018)
- "Rang and Dale's Pharmacology" Elsevier (2019)
- "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition" McGraw-Hill Education / Medical (2017)
- "Diuretics in acute kidney injury" Minerva Anestesiol (2009)
- "Inhaled mannitol for cystic fibrosis" Cochrane Database of Systematic Reviews (2018)
- "Sodium Glucose Cotransporter-2 Inhibition in Heart Failure" Circulation (2017)