What is the mechanism of action of spironolactone (aldosterone antagonist)?

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From the Guidelines

Spironolactone is a potassium-sparing diuretic that primarily works as an aldosterone antagonist, used to treat conditions like heart failure, high blood pressure, and primary hyperaldosteronism, with a typical dosing range of 25-100 mg daily. This medication blocks the effects of the hormone aldosterone, helping the body eliminate excess sodium while retaining potassium 1. It is commonly used to treat conditions such as high blood pressure, heart failure, edema (fluid retention), primary hyperaldosteronism, and certain hormonal conditions. In heart failure, it reduces mortality by preventing harmful cardiac remodeling 1. For women with polycystic ovary syndrome (PCOS) or female pattern hair loss, spironolactone helps by blocking androgen (male hormone) effects. It's also used off-label for acne in women due to its anti-androgen properties.

Some of the key benefits of spironolactone include:

  • Reducing mortality in heart failure patients by preventing harmful cardiac remodeling 1
  • Improving survival in patients with advanced heart failure (NYHA III-IV) when used in addition to ACE inhibition and diuretics 1
  • Reducing choroidal thickness and improving visual acuity in patients with central serous chorioretinopathy (CSC) 1
  • Blocking androgen effects in women with PCOS or female pattern hair loss

However, spironolactone can also have some side effects, including:

  • Increased potassium levels, which can be dangerous, especially in those with kidney problems or when combined with other potassium-retaining medications 1
  • Breast tenderness, menstrual irregularities, and frequent urination
  • Hyperkalemia, which can cause cardiac arrest, particularly in at-risk patients with diabetes mellitus, kidney and/or liver disorders, and elderly patients 1

Regular monitoring of kidney function and potassium levels is necessary while taking this medication, as dangerously high potassium levels can occur, especially in those with kidney problems or when combined with other potassium-retaining medications 1. The addition or increase in dosage of ACE inhibitors or ARBs should trigger a new cycle of monitoring, and potassium levels and renal function should be rechecked within 2 to 3 days and again at 7 days after initiation of an aldosterone receptor antagonist 1.

From the FDA Drug Label

Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. Spironolactone causes increased amounts of sodium and water to be excreted, while potassium is retained Spironolactone acts both as a diuretic and as an antihypertensive drug by this mechanism.

By competing with aldosterone for receptor sites, Spironolactone provides effective therapy for the edema and ascites in those conditions.

Spironolactone's Mechanism of Action: Spironolactone works by antagonizing aldosterone, leading to increased excretion of sodium and water, and retention of potassium.

  • It acts as a diuretic and an antihypertensive drug.
  • It provides effective therapy for edema and ascites in conditions such as congestive heart failure, hepatic cirrhosis, and nephrotic syndrome 2.

From the Research

What is Spironolactone

Spironolactone is a medication that has been used for over half a century as a 'potassium-sparing diuretic' 3. It is primarily used in patients with ascites, but its use has expanded to include other conditions such as:

  • Primary aldosteronism, a common form of secondary hypertension 3
  • Heart failure with a reduced ejection fraction, where it has been shown to be beneficial in addition to standard therapy 3, 4, 5
  • Diastolic heart failure, where it is being increasingly used despite the failure of the TOPCAT trial 3
  • Hypertension resistant to three conventional antihypertensives, including a diuretic, where it has been proven to be effective 3, 6
  • Pulmonary hypertension/fibrosis and cancer, where it may play a useful role 3

How Spironolactone Works

Spironolactone works as a competitive aldosterone receptor antagonist (ARA) 4. It is partially absorbed and extensively metabolized by the liver, with its therapeutic properties attributable to its active metabolite canrenone 4. At therapeutic doses, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases 4.

Benefits and Risks of Spironolactone

The benefits of spironolactone include:

  • Improvement in blood pressure control in patients with resistant hypertension 6
  • Reduction in mortality and hospitalization for cardiac causes in patients with heart failure 4, 5
  • Symptomatic relief in patients with heart failure and preserved ejection fraction 5 However, spironolactone also carries risks, including:
  • Hyperkalemia, particularly in patients with renal insufficiency or those taking other medications that increase potassium levels 6, 7
  • Gynecomastia, decreased libido, and impotence in men, and menstrual irregularities in women 4
  • Renal insufficiency, which requires monitoring 6

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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