What is the mechanism of action of spironolactone?

From the Guidelines

Spironolactone works primarily as a potassium-sparing diuretic by blocking the mineralocorticoid receptor (aldosterone receptor) in the distal tubules and collecting ducts of the kidney, preventing sodium reabsorption and potassium excretion, and leading to increased sodium and water excretion while conserving potassium. This mechanism of action explains its clinical effects of reducing blood pressure and edema while maintaining or increasing serum potassium levels 1. Spironolactone also has anti-androgenic properties by binding to androgen receptors and inhibiting testosterone production, making it useful for conditions like hirsutism, acne, and female pattern hair loss 1. Additionally, it blocks aldosterone's effects on the heart and blood vessels, providing cardioprotective benefits in heart failure by reducing fibrosis and remodeling 1. Some key points to consider when prescribing spironolactone include:

• Monitoring serum potassium levels regularly, especially in patients with renal impairment or those taking other potassium-sparing medications, as hyperkalemia is a potential serious side effect 1.
• Being aware of the potential for menstrual irregularities, breast tenderness, and other side effects, particularly in women 1.
• Considering the use of spironolactone in combination with other medications, such as oral contraceptives, for the treatment of acne and other conditions 1.
• Avoiding the use of spironolactone in pregnancy due to the potential risk of feminization of a male fetus 1. Overall, spironolactone is a valuable medication for the treatment of various conditions, including heart failure, hypertension, and acne, but its use requires careful consideration of the potential benefits and risks.

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.

The mechanism of action of spironolactone is as an aldosterone antagonist, which leads to increased excretion of sodium and water, and retention of potassium. This results in its effects as both a diuretic and an antihypertensive drug 2.

• The primary action is through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule.
• This action is the basis for its use in treating conditions such as edema and ascites in conditions like congestive heart failure, hepatic cirrhosis, and nephrotic syndrome.

From the Research

Mechanism of Action of Spironolactone

The mechanism of action of spironolactone is primarily as a competitive aldosterone receptor antagonist (ARA) 3. This means it works by blocking the effects of aldosterone, a hormone that plays a crucial role in regulating blood pressure and electrolyte balance. Key aspects of its mechanism include:

• Blocking the action of aldosterone at its receptor sites, which are found in various tissues including the kidneys, heart, and blood vessels 4.
• Reducing the reabsorption of sodium and water and increasing the excretion of potassium in the kidneys, which helps to lower blood pressure and reduce fluid retention 3.
• Having direct effects on the cardiovascular system, including reducing vascular resistance and reactivity to vasopressor agents, and producing a direct inotropic action on the heart 4.
• Counteracting the effects of aldosterone on myocardial fibrosis, which is important in the management of heart failure 3, 5.

Clinical Implications

The use of spironolactone has been shown to be beneficial in various clinical conditions, including:

• Primary hyperaldosteronism, where it is used to control blood pressure and hypokalemia 3.
• Heart failure, where it has been shown to reduce mortality and morbidity when used in combination with other treatments like ACE inhibitors 3, 6.
• Essential hypertension, where it can be used as part of the treatment regimen, especially in patients who do not respond adequately to other treatments 3, 5.
• Conditions associated with edema, such as cirrhosis of the liver, where it helps to reduce fluid retention 3.

Safety Considerations

While spironolactone is generally well-tolerated, there are potential side effects and safety considerations to be aware of, including:

• Hyperkalemia, which can be life-threatening, especially when spironolactone is used in combination with ACE inhibitors or in patients with renal insufficiency 7.
• Endocrine side effects, such as gynecomastia, decreased libido, and menstrual irregularities, due to its anti-androgenic and progestational actions 3.
• The need for careful monitoring of serum potassium levels and renal function, especially in high-risk patients 7.