A mineralocorticoid receptor antagonist (MRA) is a prescription diuretic that counteracts the effects of aldosterone, a hormone produced by the adrenal glands. Aldosterone helps manage the body’s fluid and electrolyte balance. By blocking this hormone, MRAs help regulate blood pressure and reduce fluid retention, which can benefit individuals with certain cardiovascular or kidney-related issues. These medications are often prescribed alongside other drugs to alleviate strain on the heart and other body systems.
Mechanism of Action
Aldosterone signals the kidneys to retain sodium and excrete potassium. When the body holds onto sodium, it also retains water, which increases the volume of fluid in blood vessels and can raise blood pressure. This process is a natural way for the body to regulate blood pressure.
Aldosterone delivers its instructions by binding to mineralocorticoid receptors, which are proteins found in the kidneys, heart, and blood vessels. This binding initiates cellular events that lead to sodium and water retention.
An MRA acts as a competitive blocker at these receptor sites. Like a key that fits a lock but cannot turn it, the MRA occupies the receptor, preventing aldosterone from binding. This action inhibits the reabsorption of sodium and encourages water to be excreted from the body as urine.
This blockade leads to a decrease in fluid volume and a reduction in blood pressure. By preventing aldosterone’s action, MRAs also decrease potassium excretion, which is why they are known as “potassium-sparing” diuretics.
Medical Applications
Mineralocorticoid receptor antagonists are used to treat several medical conditions, primarily related to the cardiovascular and renal systems.
For individuals with heart failure, the heart’s pumping ability is compromised, leading to fluid buildup. By reducing the fluid retention promoted by aldosterone, MRAs decrease congestion and make it easier for the heart to pump. This can lead to improved symptoms, exercise capacity, and quality of life.
MRAs are also prescribed for high blood pressure, particularly for resistant hypertension where other drugs have not been effective. By preventing aldosterone-driven sodium and water retention, they help lower blood pressure. Their mechanism provides a different pathway for blood pressure control, making them a useful addition to treatment regimens.
In chronic kidney disease (CKD), especially when associated with type 2 diabetes, MRAs can help protect the kidneys. Aldosterone can contribute to inflammation and fibrosis (scarring) in the kidneys over time. By antagonizing these effects, certain MRAs can help slow the progression of kidney disease and reduce protein leakage into the urine, a marker of kidney damage.
MRAs are also used to treat primary aldosteronism, a condition where the adrenal glands overproduce aldosterone. This excess hormone leads to high blood pressure and low potassium levels. MRAs directly block the hormone causing the problem, making them a primary treatment for this condition.
Common Types and Examples
Mineralocorticoid receptor antagonists are categorized by their chemical structure as either steroidal or non-steroidal agents. Each type has distinct properties and potential side effects.
Spironolactone
Spironolactone is the oldest steroidal MRA. While it effectively blocks aldosterone receptors, its structure is non-selective and can also interact with androgen and progesterone receptors. This lack of selectivity is responsible for some of its hormonal side effects.
Eplerenone
Eplerenone is a newer steroidal MRA designed to be more selective for the mineralocorticoid receptor. It has less affinity for other steroid hormone receptors. This selectivity means eplerenone is less likely to cause the hormonal side effects associated with spironolactone.
Finerenone
Finerenone is a non-steroidal MRA with a different chemical structure and mechanism of action than steroidal agents. It has anti-inflammatory and anti-fibrotic effects in addition to blocking the aldosterone receptor. Finerenone is noted for its benefits in patients with chronic kidney disease and type 2 diabetes, helping reduce the risk of kidney function decline.
Potential Side Effects and Monitoring
While effective, mineralocorticoid receptor antagonists can cause side effects, the primary one being hyperkalemia (elevated blood potassium). Because these drugs are “potassium-sparing,” levels can become too high. This can lead to serious health problems, including muscle weakness, fatigue, and life-threatening heart rhythm disturbances.
The risk of hyperkalemia is higher in individuals with kidney problems or those taking other medications that increase potassium, like ACE inhibitors or ARBs. Patient selection and education are important when prescribing MRAs, as symptoms of high potassium can be subtle and require medical supervision.
Other side effects are related to the specific MRA. Because spironolactone is non-selective, it can cause hormonal effects like gynecomastia (breast enlargement) in men or menstrual irregularities in women. Eplerenone has a much lower risk of these side effects.
Due to the risk of hyperkalemia, regular monitoring is a standard part of MRA treatment. Patients require routine blood tests to check potassium levels and assess kidney function. These tests are performed before starting the medication, shortly after beginning treatment, and periodically thereafter. Monitoring allows healthcare providers to adjust treatment as needed to ensure safety and effectiveness.