Overview
This lecture reviews aldosterone antagonists, focusing on their mechanisms, clinical uses, differences, side effects, and considerations in hypertension and heart failure management.
Background on Hypertension
- Hypertension is multifactorial: autonomic, cardiac, vascular, and hormonal (including plasma volume) factors contribute.
- Multiple drug classes are often needed to target different mechanisms in treating hypertension.
Aldosterone Antagonists: Types and Mechanism
- Main drugs: Spironolactone (Aldactone) and Eplerenone (Inspra).
- These drugs competitively inhibit mineralocorticoid receptors in the distal convoluted tubule of the nephron.
- Blocking these receptors reduces sodium and water reabsorption, lowering plasma volume and blood pressure.
- Spironolactone also inhibits androgen receptors, causing unique side effects like gynecomastia.
Renin-Angiotensin-Aldosterone System (RAAS) Overview
- Low kidney perfusion triggers renin release, activating the RAAS pathway.
- Angiotensin II increases vasoconstriction and stimulates aldosterone release from the adrenal glands.
- Aldosterone increases sodium and water reabsorption at the distal nephron, raising plasma volume and blood pressure.
- Aldosterone antagonists block this effect directly at the receptor.
Clinical Uses and Indications
- Spironolactone: used for hypertension, heart failure (especially with reduced ejection fraction), hypokalemia, hyperaldosteronism, cirrhosis with ascites, acne, and hirsutism.
- Eplerenone: mainly indicated for hypertension and post-MI heart failure with reduced ejection fraction.
- Spironolactone's androgen inhibition benefits women with hirsutism but causes gynecomastia in men.
Key Side Effects and Drug Considerations
- Both drugs can cause hyperkalemia, especially with ACE inhibitors, ARBs, or in renal impairment.
- Eplerenone is metabolized by CYP3A4, increasing potential drug interactions.
- Spironolactone has higher risk of gynecomastia due to androgen receptor binding.
- High doses of spironolactone are needed in ascites, increasing hyperkalemia risk—often combined with furosemide to balance potassium.
Practical Dosing and Management
- Typical target doses: ~50 mg for hypertension/heart failure, higher for ascites (up to 200 mg).
- For every 100 mg of spironolactone, use 40 mg furosemide to mitigate hyperkalemia in ascites.
- Avoid salt substitutes (often contain potassium), as they increase hyperkalemia risk.
- NSAIDs may reduce efficacy by decreasing renal blood flow and activating RAAS.
Key Terms & Definitions
- Aldosterone Antagonists — drugs that block aldosterone receptors to reduce sodium/water reabsorption and lower blood pressure.
- Gynecomastia — enlargement of male breast tissue, often due to androgen receptor inhibition.
- Hyperkalemia — elevated blood potassium, a major risk with these drugs.
- RAAS — renin-angiotensin-aldosterone system, a hormone system regulating blood pressure and fluid balance.
Action Items / Next Steps
- Review RAAS pathway and role of aldosterone.
- Memorize indications and side effect differences between spironolactone and eplerenone.
- Study appropriate dosing and management for patients with heart failure and ascites.