Loop Diuretics

Always ask yourself these 5 questions when you see a drug name to help you understand how the drug works, your role as a nurse, and what information will be asked on an exam
about the drug:

Name (specifically the family name)? This will tell how the drug works.

Used for? This will tell you WHY the drug was ordered…what condition is this medication treating in your patient?

Responsibilities as the nurse? This will tell you what your role is as the nurse and what you need to monitor in the
patient.

Side effects? Know the common side effects of the medications

Education pieces for the patient? As the nurse we play a HUGE role in educating our patients on how to take the
drug, what to watch out for, and when to call the doctor.
Now, using those 5 questions let’s go over what you need to know about loop diuretics for exam:
Name?
*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.
Examples: Bumetanide, Furosemide, Torsemide with the exception of Ethacrynic acid

How 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.

To truly understand how loop diuretics work to cause diuresis and why they cause certain side effect, we need to review the basic anatomy and physiology of the nephron.

Review of the Anatomy and Physiology of the Nephron

-The nephrons are the structures in the kidneys that allow them to function and without them working properly the kidneys fail to work properly.
-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 neprhon 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 in 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).
-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 interstitum 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.
*Now let’s dive a little deeper and talk more in depth about the loop of Henle, since this is where loop diuretics
work.
The loop of Henle receives filtrate from the proximal convoluted tubule. As it flows into the descending limb, the
filtrate will become more concentrated (meaning it will lose water because it’s being reabsorbed into the blood).
The concentrated filtrate contains mainly ions (electrolytes).
Why does the filtrate lose water and become concentrated?
-The descending limb is entering into a very hypertonic environment (highly salty), and it’s ONLY permeable to water (not ions). Therefore, once the filtrate enters this area, water
will be drawn from the filtrate into the interstitium and back into the blood. The loop of Henle is responsible for reabsorbing about 15-20% of filtered water.

-Now the filtrate is concentrated and rich in ions, specifically sodium, and it flows into the ascending limb. This ascending limb wants to keep the renal medulla interstitum
hypertonic so water can be reabsorbed and cause reabsorption of ions back into the blood via various channels and transporter proteins (one cotransporter used is the NKCC2)
within the cells. The loop of Henle reabsorbs about 25% of sodium. Remember this will help keep that medulla hypertonic….if we alter how much sodium is reabsorbed the tonicity
of the medulla will decrease and this will alter water reabsorption.

*How are the ions reabsorbed back into the blood from the thick ascending limb? As the filtrate flows up the ascending limb and enters the thick part of the ascending limb, it
encounters a cotransporter protein called the Na-K-CL transporter. This cotransporter will cause reabsorption of sodium, potassium and chloride, which will go back into the
interstitium and blood (again the sodium will help keep the interstitum hypertonic).

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 it 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 transporter, 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 acts 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 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 because 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 route 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.

-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).