How Do Thiazides Work? All About Thiazide Diuretics’ Mechanism of Action

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Your body consists of55% to 60% water. And water is essential for your survival. Among other things, it helps regulate body temperature and transports important substances in the blood.

But too much water in the body can be harmful. The term edema refers to swelling in the tissues caused by fluid buildup. Edema can occur with several health conditions, including heart failure and liver or kidney damage. Somemedications can also cause edema, particularly in thefeet and ankles.

Diuretics are a broad group of medications that treat conditions that cause edema and high blood pressure (hypertension). There are several types of diuretics, including thiazides, the most commonly prescribed class. Here, we'll review thiazide diuretics' mechanism of action, what conditions they treat, and how quickly they work.

What are thiazide diuretics?

Thiazides and other diuretics are frequently referred to as "water pills" because they remove excess fluid from the body. This makes them useful medications for treating health conditions that cause fluid retention and swelling. For example, two of the most commonly prescribed thiazide diuretics - hydrochlorothiazide (Microzide) and chlorthalidone are FDA approved to treat edema from:

• Heart failure

• Liver cirrhosis

• Corticosteroid use

• Estrogen use

• Kidney conditions, including kidney failure

They're also approved to treat hypertension.

How do thiazides work?

In order to explain the thiazide diuretic mechanism of action, we first need to discuss how your kidneys work. Then, we'll talk about how thiazides treat edema and hypertension.

How your kidneys work

The primary job of the kidneys is to create urine to remove waste and extra fluid from the bloodstream. At the same time, your kidneys help you hold onto the amount of fluid and nutrients that your body needs. This includes holding onto necessary amounts of essential minerals like sodium, potassium, magnesium, and calcium.

Even though the kidneys work to maintain the right balance of water and nutrients in your body, several health conditions can throw off this balance. That's when thiazides can help.

How thiazides treat edema

Thiazides work by blocking the part of the nephrons called the sodium-chloride channel. Nephrons are "units" in the kidneys that filter the blood. There are millions of them in each kidney.

The sodium-chloride channel is found in an area of the nephron called the distal convoluted tubule (DCT). Blocking the sodium-chloride channel here prevents the kidneys from holding onto sodium (salt) as they typically would. As a result, more salt leaves your body through the urine.

Water follows salt. So as more salt leaves your body, more fluid leaves your body, which can quickly improve edema. However, thiazides can cause the body to get rid of more potassium and magnesium than usual, while retaining calcium. Sometimes, this can lead to electrolyte imbalances as a side effect.

How thiazides treat hypertension

Having a lower amount of fluid in the blood vessels decreases blood pressure. So, similar to how they treat edema, thiazides can lower blood pressureby reducing the amount of fluid in the body.

Importantly, thiazides also help lower blood pressure by widening the blood vessels, helping blood flow more easily.

Do thiazides start working immediately?

Thiazide diuretics work quickly to get rid of excess fluid. For example, hydrochlorothiazide and chlorthalidone start working within 2 to 3 hours.

If you're taking a thiazide to treat hypertension, your blood pressure levels may improve within a few days. But it can take several weeks to experience the full effects.

How do you know if your thiazide is working?

If you're taking a thiazide to treat edema, there are some signs that may indicate the medication is working. For example, you may notice you're peeing more often and that you have less swelling in your ankles and feet. Monitoring your weight daily can also help you see how well your thiazide is working to get rid of excess fluid.

If you're taking a thiazide for hypertension, there may not be obvious signs that your thiazide is working. But monitoring your blood pressure at home can help you tell if the medication is effective. Work with your prescriber to determine what your blood pressure goals are and how frequently to check your blood pressure.

How are thiazides different from other diuretics?

Loop diuretics and potassium-sparing diuretics are two other commonly prescribed types of diuretics. These diuretic groups work differently from each other and from thiazides:

• Loop diuretics: Loop diuretics, such as furosemide (Lasix), are able to get rid of more fluid than thiazides. While thiazides are generally the preferred diuretics for hypertension, loop diuretics are typically preferred in situations in which fluid overload is significant, such as with heart failure. While they're more likely to lead to dehydration and low potassium levels than thiazides, they're less likely to cause low sodium.

• Potassium-sparing diuretics: Potassium-sparing diuretics, such as spironolactone (Aldactone), aren't as effective at treating edema or hypertension as thiazides are. But they can be used to help prevent potassium loss. For example, they're sometimes taken alongside medications that can cause low potassium, including thiazides. Additionally, spironolactone has several off-label uses not mentioned here.

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