How Does Losartan Work? All About Its Mechanism of Action

Losartan (Cozaar) is one of the most commonly prescribed medications in the U.S. It’s approved to treat a few health conditions, including high blood pressure and kidney problems from diabetes. Losartan is also prescribed “off-label” for other conditions, like heart failure.

In this article, we explore losartan’s mechanism of action, or how it works. We’ll also cover how it’s used to treat a variety of conditions.

What is losartan?

Losartan belongs to a group of medications called angiotensin II receptor blockers (ARBs). ARBs treat several health conditions, including hypertension (high blood pressure). Other examples of ARBs include olmesartan (Benicar), telmisartan (Micardis), and valsartan (Diovan).

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Losartan comes as generic tables and brand-name tablets (Cozaar). Typically, it’s taken once a day, with or without food.

How does losartan work?

Losartan works by blocking angiotensin II from acting on angiotensin II receptors. But what does that mean in practical terms? Below, we’ll outline how losartan’s mechanism of action allows it to treat a variety of conditions.

How losartan works to lower blood pressure

Angiotensin II is a hormone that increases blood pressure. It does this in three major ways:

1. Constricting (tightening) the walls of your blood vessels (particularly, your arteries)

2. Signaling your adrenal glands to release aldosterone, a hormone that increases blood pressure by causing the body to hold onto sodium and water

3. Acting directly on your kidneys to decrease the amount of sodium and water that leaves the body through your urine

Combined, these effects increase blood pressure, which is where losartan comes in. Losartan blocks angiotensin II type 1 receptors, the binding sites angiotensin II attaches to. By blocking these receptors, losartan prevents the three actions discussed above and decreases blood pressure.

How losartan works to prevent strokes

The most common type of stroke is an ischemic stroke. This type of stroke is caused by a blockage in the brain or a blockage elsewhere in that body that travels to the brain. Most often, this is due to plaque buildup in a blood vessel that then breaks and forms a blood clot. These clots can block blood flow to the brain, resulting in a stroke.

Losartan treats one of the major risk factors for stroke: high blood pressure. It also helps prevent strokes by improving the health of blood vessels, making it less likely that plaque buildup worsens and forms clots that get stuck.

How losartan works to protect the heart

By lowering blood pressure, losartan also helps protect your heart. High blood pressure can damage your heart in several ways. For example, high blood pressure decreases blood flow to the heart by damaging essential arteries. Over time, this can lead to chest pain, heart attack, or heart failure.

By blocking angiotensin II, losartan can prevent or minimize “cardiac remodeling.” This is a process in which damage to the heart causes undesirable changes to its structure and function. Cardiac remodeling, which contributes to the development of heart failure, was originally thought to occur only after a heart attack. But now we know that many health conditions can cause these changes, including hypertension and inflammation in the heart (myocarditis).

How losartan works to protect the kidneys

Losartan also helps protect the kidneys in many ways, including by:

• Decreasing blood pressure, which is known to protect the kidneys and prevent kidney disease from worsening

• Decreasing the amount of protein in the urine, which is associated with kidney disease

• Decreasing certain substances that cause inflammation in the kidneys

• Decreasing blood levels of uric acid, a substance that has been linked to heart problems, diabetes, and kidney problems

When might you need to take losartan?

Losartan has several FDA-approved and off-label uses. Off-label use refers to prescribing a medication for a different condition than what it was FDA approved to treat.

To start with, losartan is FDA approved to:

• Treat high blood pressure (hypertension) in adults and children who are at least 6 years old

• Treat kidney problems from diabetes (diabetic nephropathy) in some adults with Type 2 diabetes and hypertension

• Lower the risk of stroke in some adults with hypertension and left ventricular hypertrophy (a condition in which the left side of the heart is enlarged)

Off-label uses of losartan include:

• Treating heart failure in people who can’t tolerate other, first-choice medications like sacubitril / valsartan (Entresto) or lisinopril (Zestril)

• Treating kidney disease not caused by diabetes

• Preventing further damage after a heart attack in people who can’t take angiotensin-converting enzyme (ACE) inhibitors

• Treating Marfan syndrome (an inherited condition that can cause high blood pressure)

How long does it take losartan to work?

Losartan may start working with your first dose, but you won’t feel its full effects immediately.

If you’re taking losartan for hypertension, you’ll likely notice a drop in blood pressure within 1 week after starting treatment. But it may take up to 3 to 6 weeks for the medication’s full blood-pressure-lowering effects to take hold.

The effects of losartan may be less obvious if you’re taking it for a condition other than hypertension. But this doesn’t mean you should stop taking the medication. If you have any concerns about whether losartan is working for you, talk to your healthcare provider.

How is losartan different from other blood pressure medications?

There are many medications that treat hypertension. These include:

• ACE inhibitors

• Diuretics (water pills)

• Calcium channel blockers

• Beta blockers

Below, we’ll focus on how losartan is different from ACE inhibitors and diuretics, since these are two common types of blood pressure medication.

Losartan vs. ACE inhibitors

ACE inhibitors are the most similar group of medications to ARBs, including losartan. Examples of ACE inhibitors are lisinopril and benazepril (Lotensin).

ACE inhibitors and ARBs treat many of the same conditions and work in similar ways. They both block the actions of angiotensin II. But ACE inhibitors block the enzyme (protein) that is required to produce angiotensin II, whereas ARBs block angiotensin II receptors.

In general, ACE inhibitors and ARBs work similarly well. But ACE inhibitors are considered to have more side effects, including cough. While losartan can also cause cough, it’s not as common.

Losartan vs. diuretics

Diuretics lower blood pressure by increasing the amount of fluid and sodium that leaves your body. Different diuretics work in slightly different ways, and some have a stronger effect on blood pressure than others. Because of their effects on blood pressure, thiazide diuretics, like hydrochlorothiazide (Microzide) and chlorthalidone (Thalitone), are first-choice treatment options for treating hypertension.

Diuretics work differently than losartan and have their own side effects. One of the most notable risks with diuretics is electrolyte changes. Diuretics can cause:

• Hypokalemia (low potassium levels) or hyperkalemia (high potassium levels), which is less common but seen with some diuretics like spironolactone (Aldactone)

• Hyponatremia (low sodium levels)

• Hypomagnesemia (low magnesium levels)

• Hypercalcemia (high calcium levels)

While losartan can cause hyperkalemia (high potassium), it’s not known to cause other electrolyte changes. Unlike thiazides, losartan also doesn’t cause sensitivity to the sun, and it’s less likely to cause sexual problems. In fact, losartan may even improve sexual problems in some people with high blood pressure. Both losartan and thiazides can cause dizziness and tiredness, however.

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Written by:

Alex Brewer, PharmD, MBA

Alex Brewer, PharmD, MBA, is a licensed pharmacist specializing in chronic disease and health and wellness. Upon completing his residency, he worked in the managed care field, conducting medication therapy management and adherence counseling sessions with Medicaid, Medicare, and private insurance patients, before transitioning to a career in medical writing.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Christina Palmer, MD

Christina Palmer, MD, is a board-certified family physician with a special interest in chronic care management, women’s health, mental health, and preventive care. She has over 10 years of experience in primary care research, innovation, and practice.

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