Loop Diuretics’ Mechanism of Action: How Do These Water Pills Work

Diuretics, also called water pills, are a broad group of medications that relieve edema (fluid buildup). They treat a variety of health conditions, including hypertension (high blood pressure) and swelling from conditions like liver disease and heart failure. But all diuretics aren't created equally. There are key differences among the different types of diuretics regarding how they work, what they treat, and their potential side effects.

In this article, we'll focus on a class of diuretics called loop diuretics. We'll discuss loop diuretics' mechanism of action, what they treat, and other key details about these medications.

What are loop diuretics?

Loop diuretics are a group of medications that help the body get rid of fluid. They're prescribed to treat edema from several health conditions, including heart failure. In fact, loop diuretics are first-choice treatments for edema related to heart failure.

Loop diuretics may also be used to treat edema from cirrhosis (scarring of the liver) and kidney disease. Often, loop diuretics are used to treat cirrhosis when another diuretic, called spironolactone (Aldactone), doesn't work on its own.

Loop diuretics are also FDA approved to treat hypertension. They aren't first-choice medications for hypertension, but they may be helpful in certain instances. For example, people who have hypertension and heart failure or moderate-to-severe kidney disease may benefit from a loop diuretic.

The table below lists various loop diuretics and their forms.

How do loop diuretics work?

To understand loop diuretics' mechanism of action, you first need to understand the basics of how your kidneys work.

How the kidneys work

As blood travels through the body, it transports oxygen and other important nutrients into cells. It also transports waste out of the cells. That waste needs somewhere to go so it doesn't build up in the body.

This is the key responsibility of the kidneys: filtering excess fluid and waste out of the blood and into the urine. They also return necessary fluid and nutrients back to the body.

The kidneys are made up of millions of basic units called nephrons. Each nephron has two main parts, one of which is called a tubule. The tubule is the portion of the nephron that returns nutrients and some fluid back to the body, leaving waste in the urine.

This is where loop diuretics come in. They work in a part of the tubule called the loop of Henle. Within the loop of Henle, these diuretics block what is known as the sodium-potassium-chloride cotransporter. This is a special type of protein that moves sodium, potassium, and chloride in and out of cells.

When loop diuretics block this transporter, they stop the kidneys from returning these electrolytes back to the body. As a result, these electrolytes get removed through the urine. And since water likes to follow sodium wherever it goes, excess fluid in the body is also removed through the urine, relieving edema. Removing excess fluid from the body is also how loop diuretics lower blood pressure.

Do loop diuretics work immediately?

Loop diuretics start working quickly. When taken by mouth, they typically take 30 minutes to 1 hour to start working. When given as an injection, loop diuretics start working immediately. This form is typically only used in hospitals and medical clinics, though.

How do you know if your loop diuretic is working?

One sign your loop diuretic is working is having to pee within an hour after taking a dose. Because a loop diuretic can cause you to pee more, it's typically recommended to avoid taking a dose close to bedtime. Otherwise, you may find yourself waking up throughout the night to go to the bathroom.

Talk to your prescriber about how to tell that your loop diuretic is working long term - and possible signs that it's not working well enough. They may want you to monitor your weight to ensure it's not increasing unexpectedly, which may indicate fluid buildup. They may also ask you to check your blood pressure at home and watch for signs of swelling.

It's also a good idea to watch for signs that your loop diuretic is working too well. Watch for symptoms of dehydration, such as increased thirst, dry mouth, and dizziness. If you have severe dehydration, you may experience confusion, dark urine, and extreme lightheadedness. In this case, head to the closest emergency room. You may need IV fluids and other supportive measures.

While you're being treated with a loop diuretic, your prescriber will order blood tests periodically to check your levels of various electrolytes. Along with dehydration, loop diuretics can cause electrolyte abnormalities, which we discuss more below. Abnormal electrolyte levels can cause a number of health concerns, including heart problems. So it's good to test levels periodically to catch any problems before they get serious.

How are loop diuretics different from other diuretics?

Loop diuretics are considered stronger than other types of diuretics because they are able to get rid of more fluid. Other diuretic classes include:

• Thiazide diuretics, such as hydrochlorothiazide (Microzide)

• Aldosterone antagonists, such as spironolactone

• Potassium-sparing diuretics, such as amiloride (Midamor)

Uses

As previously mentioned, loop diuretics aren't first-choice treatments for hypertension. Thiazide diuretics are the go-to diuretic for lowering blood pressure.

On the other hand, loop diuretics are preferred for health conditions involving edema. This is because they get rid of more fluid than thiazides. So if you have heart failure and need a diuretic, your prescriber will likely choose a loop diuretic (like furosemide) over a thiazide diuretic (like hydrochlorothiazide).

While loop diuretics are more effective at treating edema, spironolactone is helpful for preventing potassium loss and also has several off-label uses.

Side effect differences

Because loop diuretics get rid of the most fluid, they're more likely to cause dehydration and certain electrolyte abnormalities, such as hypokalemia (low potassium). Other common diuretics, called thiazides, can also cause electrolyte problems and may be more likely to cause hyponatremia (low sodium). But in general, the risk of dehydration and electrolyte problems is highest with loop diuretics.

One unique loop diuretic side effect is ototoxicity (inner ear damage). Ototoxicity can affect your ability to hear and your balance. The risk for ototoxicity is highest with ethacrynic acid, but it can happen with any loop diuretic. While ototoxicity and hearing loss caused by loop diuretics is usually reversible, it can lead to permanent deafness in rare cases.

One thing loop and thiazide diuretics share is they should be taken with caution if you're allergic to sulfonamides ("sulfa drugs"). Thiazides and loop diuretics contain sulfonamides, so they can trigger a reaction if you have a sulfa allergy. Ethacrynic acid is an exception: It doesn't contain sulfonamides and is safe to take if you have a sulfa allergy.