Loop diuretics: Uses, common brands, and safety info

Loop diuretics are a class of medications used to cause diuresis, or increased urine flow. They differ from other types of diuretics in how they increase urine production. Other diuretic classes include thiazide diuretics, carbonic anhydrase inhibitors, and potassium-sparing diuretics. Loop diuretics are considered to be the most potent type of prescription diuretic.

There are conditions where the use of diuretics is necessary to help remove excess fluid from your body. One example is edema, or the accumulation of excessive fluid in your body tissues. This may present as swelling in the ankle or lower extremities and can be due to underlying conditions such as congestive heart failure. In this instance, the heart isn’t functioning well enough to provide efficient circulation of the fluid back to the kidneys to be removed. 

Other conditions where loop diuretics are helpful are liver disease, kidney disease, and high blood pressure. It is possible that a patient may suffer from more than one condition requiring diuresis at the same time, and some patients may require the use of more than one type of diuretic for adequate diuresis. This article will discuss how loop diuretics work, their safety, and what you should know about taking them.

What are loop diuretics?

Loop diuretics are prescription medications that cause an increase in urine output. Diuresis is necessary for some medical conditions when there is fluid retention in the body’s tissues. 

Loop diuretics are named in reference to the portion of the renal system where they exert their mechanism of action, the ascending limb of the loop of Henle. The loop of Henle is named after the scientist who discovered it, Friedrich Gustav Jakob Henle. Loop diuretics have been in use since the 1960s and have an important role in the treatment of heart failure, lung disease, pulmonary edema, nephrotic syndrome, renal failure, and hypertension.

How do loop diuretics work?

The loop of Henle has a descending and ascending portion. There are sodium-potassium-chloride cotransporters on the thick ascending limb portion of the loop which are responsible for maintaining the electrolyte concentration of the fluid moving through the kidneys. Loop diuretics inhibit this cotransporter by competing at the chloride receptor. Therefore sodium, potassium, and chloride are not reabsorbed in the kidney, and more water is needed and drawn into the nephron to dilute the increased electrolyte presence. This process of pulling water from the body tissues into the nephron results in the excretion of these electrolytes and increased urinary output. 

Loop diuretics are also thought to block the reabsorption of calcium and magnesium as well. This may lead to decreased calcium levels (hypocalcemia) and decreased magnesium levels (hypomagnesemia).

The pharmacokinetics and bioavailability of loop diuretics are important when making a treatment choice for a life-threatening condition. Diuresis will begin much more quickly, generally within 5 minutes, when given by intravenous route versus the oral route. The rate of absorption when a drug is given orally is sometimes erratic and may take up to an hour to cause diuresis. 

What are loop diuretics used for?

• Ascites

• Edema

• Heart failure

• High blood pressure

• Hypercalcemia

• Nonobstructive oliguria

• Oliguria

• Peripheral edema

• Pulmonary edema

• Renal failure (decreased glomerular filtration)

• Renal transplant

• Chronic kidney disease

Types of loop diuretics

Sulfonamide-derived loop diuretics

These loop diuretics contain a sulfonamide group within their chemical structure. If a patient is allergic to sulfa drugs, these loop diuretics could trigger an allergic reaction. Please let your prescriber know of all of your drug allergies.

Examples: Bumetanide, furosemide, torsemide

Non sulfonamide-derived loop diuretics

This type of loop diuretic is free of a sulfonamide group in its chemical structure. This would be the safest type of loop diuretic for a patient with a sulfa allergy.

Example: Ethacrynic acid

Who can take loop diuretics?

Adults

Adult men and women can take loop diuretics. If the patient has a known hypersensitivity to any component of the loop diuretic, they should avoid this medication. Patients with a pre-existing electrolyte imbalance should correct their electrolyte status prior to initiating treatment with loop diuretics.

Seniors

Seniors can take loop diuretics. The electrolyte status of seniors can be more delicate and should be monitored closely. While loop diuretics may be used for their antihypertensive effects, caution should be used in patients with pre-existing hypotension, or low blood pressure, as loop diuretics may lower the blood pressure even further.

Children

Furosemide, bumetanide, and ethacrynic acid are approved for use in children for some approved indications such as heart or renal failure. Torsemide is not approved for use in children.

Neonates

Furosemide, bumetanide, and ethacrynic acid are approved for use in neonates for a limited number of conditions and very specific dosing. Torsemide is not approved for use in neonates.

Are loop diuretics safe?

Loop diuretic recalls

• SCA Pharmaceuticals: Voluntary recall of furosemide due to presence of precipitate, March 2020

Restrictions

Do not take loop diuretics if you have a history of hypersensitivity reactions to any loop diuretics. Do not take furosemide, torsemide, or bumetanide if you have a known sulfa drug allergy. 

Excessive diuresis may cause dehydration and deplete blood volume and electrolytes. This can cause a circulatory collapse and can be fatal in some cases. It is important to maintain hydration when taking any diuretic. Patients should watch for signs of dehydration and electrolyte imbalance such as dry mouth, thirst, weakness, lethargy, drowsiness, muscle pains or cramps, low blood pressure, nausea, and vomiting. Seek medical attention immediately if you suspect dehydration. 

Patients taking diuretics are prone to postural hypotension, sometimes called syncope, which is a lightheaded or dizzy feeling upon standing. This can be managed in most cases by rising slowly and gripping something for stabilization. If you have extreme experiences of dizziness, seek medical attention. Patients who experience postural hypotension are at an increased risk of falling upon standing.

Patients who have been diagnosed with diabetes mellitus may experience increased blood glucose levels and have altered urine glucose readings. Make sure your physicians are aware you take loop diuretics.

Loop diuretics may cause your skin to be more sensitive than normal to sunlight. It may be necessary to take precautions against sunburns while taking loop diuretics.

Your clinician, specifically cardiology or nephrology specialists, may order frequent lab tests to monitor your kidney and liver function as well as to watch your cardiac and electrolyte status while on loop diuretics.

Can you take loop diuretics while pregnant or breastfeeding?

Furosemide and bumetanide are Food and Drug Administration category C, meaning that studies have shown some potential for harm during pregnancy. The use of these loop diuretics should be limited to only when absolutely necessary when pregnant. This holds true for breastfeeding mothers as well because they do cross into breast milk.

Torsemide and ethacrynic acid are category B, meaning there are no well-controlled clinical trials to determine safety. These drugs should still be used cautiously and only when necessary. Your healthcare provider can provide more information on whether it would be safe for you to take a loop diuretic while pregnant.

Are loop diuretics controlled substances?

No, loop diuretics are not controlled substances.

Common loop diuretics side effects

Loop diuretics can cause a variety of adverse effects. These side effects are mostly related to fluid and electrolyte loss or depletion, and they may vary in severity between each drug in the class and the dosing prescribed for your condition. The prevalence of side effects may increase with high doses of loop diuretics. Some side effects of loop diuretics can be severe and life-threatening.

The most common side effects are:

• Hyperuricemia

• Hypochloremia

• Hypokalemia

• Azotemia

• Hyponatremia

• Elevated creatinine

• Hyperglycemia

• Electrolyte abnormalities

• Muscle cramps

• Dizziness

• Hypotension

• Headache

• Nausea

• Photosensitivity

• Increased aldosterone levels

The more severe side effects are:

• Severe hypokalemia

• Severe electrolyte imbalance

• Metabolic alkalosis

• Hypovolemia

• Dehydration

• ECG abnormalities

• Renal failure

• Hepatic encephalopathy

• Thrombocytopenia

• Arrhythmia

• Ototoxicity

• Pancreatitis

• Stevens-Johnson syndrome

How much do loop diuretics cost?

The four loop diuretics are each available generically and generally considered very affordable. While cash prices may vary greatly between pharmacies, and insurance copays may vary depending on your plan and network, SingleCare offers savings coupons that can save you up to 80% off retail prescription drug prices. A one-month supply of furosemide can be just under $3 with a SingleCare savings card. Ethacrynic acid may be the most expensive of the loop diuretics, but the SingleC