NCM-106 | Loop diuretics

PHARMACOLOGY 💊
Loop diuretics are medications that help remove extra fluid volume from the blood
through increased urination. This review will discuss the mechanism of action of loop
diuretics, what conditions they treat, nursing implications, side effects, and patient
education.

Loop Diuretics

● Loop: these medications work on the Loop of Henle in the nephron

(specifically the thick ascending limb).
● Diuretic: the goal is to increase urinary output by limiting how parts of the
nephron reabsorb sodium. Hence, if we don’t reabsorb much sodium back
into the blood, it will stay in the filtrate within the nephron, and this will keep
more water in the filtrate too…hence increasing urine production.

Loops diuretics are the most powerful of all the types of diuretics when compared to
thiazides and potassium-sparing diuretics.

Loop diuretic generic medication names end with NIDE or MIDE.

How do these drugs work? They inhibit the Na-K-Cl (NKCC2) cotransporter protein
found in the thick ascending limb of the loop of Henle from transporting sodium,
potassium, and chloride into the cell for reabsorption. Therefore, by inhibiting this
transporter, it will prevent these ions (also called electrolytes) from being reabsorbed
into the blood.

Result of Inhibiting NKCC2? It increases sodium concentration in the filtrate. This will
decrease how the nephron is able to reabsorb water. Why? It decreases the tonicity of
the medulla interstitium, which is normally hypertonic, and this will cause the collecting
ducts and loop of Henle to reabsorb less water from the filtrate. Therefore, more water
leaves the nephron as urine.

Review of the Anatomy and Physiology of the Nephron

There are millions of nephron units in each kidney. They function to filter the blood and
manage the amount of water, ions, and waste in the blood. These substances filtered by
the nephron will either be reabsorbed into the blood or stay in the filtrate where they will
be excreted as urine.

The nephron is divided into several parts, and each part has its own unique role for
tweaking the filtrate created by the glomerulus until it is just what the body needs and
what it doesn’t need it will be excreted as urine.
The parts of the nephron are:

● afferent arteriole: delivers blood via the renal artery to the nephron so it
can be filtered
● efferent arteriole: takes filtered blood away from the nephron after it has
been filtered
● glomerulus: filters the blood and creates the filtrate which contains ions,
water, and waste
● bowman’s capsule: collects the filtrate as it drips down from the
glomerulus
● proximal convoluted tubule: the first tubule that starts tweaking the filtrate
by reabsorbing ions, water, etc.
● NOTE: these parts of the nephron hang out in the renal cortex
of the kidneys. This provides an ISOtonic environment where
the sodium concentration is equal inside the nephron (hence
the filtrate) and outside of it.
● However, as the filtrate progresses and enters into the loop of
Henle, it enters into the renal medulla, which is a very salty
(HYPERtonic) environment. This environment is necessary for
water reabsorption by descending loop of henle and the
collecting ducts.
● loop of Henle: it has a descending and ascending limb
● The descending limb of the loop of Henle is only permeable
to water (not ions). While the ascending limb (especially the
thick ascending limb) is only permeable to ions rather than
water.
● The thick ascending limb is where loop diuretics work.
● distal convoluted tubule: the filtrate is now back in an isotonic
environment for some more tweaking…the renal cortex.
● collecting ducts: this is the last part of the nephron where the filtrate is
finally tweaked. Ions and water will be reabsorbed. The last part of the
collecting duct is found in the medulla interstitium and will play a role in one
last function of water reabsorption.
● renal pelvis: filtrate exits the nephron at this location and goes to the
ureters and is urinated out.

How do Loop Diuretics Affect this Process?

As noted above, these drugs inhibit the NKCC2 cotransporter. This results in inhibiting
the reabsorption of these ions. Therefore, because sodium is not being reabsorbed like
it should, the interstitium will lose its tonicity (won’t be as hypertonic) and this will affect
how much water is reabsorbed by the loop of Henle and collecting ducts. The result is
that more water leaves via the filtrate rather than go back into the blood.

How do Loop Diuretics Lead to Electrolyte Imbalances…like hypokalemia,

hypocalcemia, and hyperuricemia?
Because the NKCC2 cotransporter is being inhibited it will affect how other ions are
reabsorbed back into the blood, specifically calcium and magnesium. Since the
ascending loop of Henle is only permeable to ions, it has other transporters,
cotransporters, and channels working together to make this ion exchange process
happen. Due to this, a positive potential is created in the nephron’s lumen which will act
as this electrical concentrated gradient that will force out calcium and magnesium
(positively charged ions) of the filtrate and into the blood.

BUT if the NKCC2 is inhibited, it will make the nephron’s lumen neutral and there won’t
be this force created to push calcium and magnesium back into the cell to be
reabsorbed. This can lower calcium and magnesium levels….especially calcium levels.

Another thing is that because the filtrate will stay concentrated with these ions,
specifically the sodium, it will affect how the distal part of the distal convoluted tubule
deals with the sodium. Normally, when the filtrate flows into this area from the loop of
Henle it is not high in sodium, but now it is because the NKCC2 cotransporter has been
inhibited.

This distal tubule uses a transporter to reabsorb sodium, and it’s influenced by
aldosterone for reabsorption of sodium. So, the higher the content of sodium the more
enhanced it will work. Therefore, it will reabsorb sodium, but to do this it must exchange
potassium and hydrogen ions, which will be excreted into the filtrate via the urine. It can
lead to HYPOkalemia and metabolic alkalosis (because of the loss of hydrogen ions).

And lastly it affects how the proximal convoluted tubule deals with urate (this is from uric
acid). It can cause increased reabsorption of urate, which can increase uric acid levels
in the blood “hyperuricemia” and led to a gout attack.

Used for?

Most of the time loop diuretics are ordered when a patient is experiencing fluid volume
overload in conditions like:

● Heart failure
● Liver impairment (ascites is present)
● Pulmonary edema
● Hypertension (not as effective as thiazides though)
● High calcium levels (hypercalcemia)

Responsibilities of a Nurse?

Patient will be losing fluid in the form of urine: watch for signs of dehydration (removing
too much fluid)

● Vitals (elevated heart rate and low blood pressure SBP <90)
 ● Monitor closely the patient’s intake and output: always strictly measure
urine output by having men urinate in a urinal and women to urinate in a
toilet hat (some patients may have a catheter).
● Daily weights (this is the best indicator of how much fluid the patient is
losing). Weigh the patient at the same time every day with the same scale.

Monitor labs:

● Assess for electrolytes imbalances and renal function. Most hospitalized

patients will have a daily BMP drawn:
● monitor for hypokalemia (normal level is 3.5-5 mEq/L)
● Many patients will experience low potassium
levels and will need potassium supplements while
taking a loop diuretic. Always check the potassium
result before giving the next dose…especially if
the patient is taking Digoxin cause hypokalemia
increases Digoxin Toxicity.
● hypocalcemia
● hyponatremia
● If the patient is taking Lithium, monitor for Lithium
toxicity because low sodium levels in the blood
can increase Lithium toxicity. A normal Lithium
level is 0.5-1.2 mmol/L.
● hypomagnesemia
● Monitor for signs of gout due to high uric acid that can occur with this
medication.

Administer IV routes very slowly (most commonly used is Furosemide) due to the risk of
causing ototoxicity (damage to inner ear).

Provide easy access to the bathroom (prevent falls) and avoid giving a dose right before
bedtime (this interrupts sleep and increases the risk of falling).

Assess the effectiveness of the medication: decrease in edema, clearer lung fields,
decrease weight etc.

Side effects?

Hypokalemia, hypocalcemia, hypotension, increase urination, hyperuricemia,

hyponatremia, hypomagnesemia, ototoxicity
Education?

● Teach to be aware of signs and symptoms of dehydration (excessive thirst,

fatigue, no urination, hypotension), and how to measure blood pressure
and heart rate at home.
● Consuming a healthy diet that includes foods with potassium because
this medication can lower potassium levels.
● Changing positions slowly due to orthostatic hypotension that can occur
because of the change of fluid volume in the body.
● Monitoring weight daily (most patients taking a loop diuretic have heart
failure so it is important they measure their weight daily and contact their
doctor if they gain 3 lbs or more in 1 day…this could mean they’re retaining
fluid)