Channel Your Enthusiasm
The 2023 NKF Clinical Meeting Live Recording: Diuretic Draft
Podcast summary created with Snipd AI
Quick takeaways
- Spironolactone's unique RNA synthesis impact and delayed effect differentiate it from traditional diuretics.
- Combining spironolactone with other diuretics provides comprehensive nephron blockade for heart failure treatment.
- Geller syndrome showcases spironolactone's agonist role in blood pressure regulation due to aldosterone receptor mutations.
- Spironolactone's anti-androgen properties attract transgender individuals for hair and breast modifications.
Deep dives
History and Mechanism of Mineralocorticoid Receptor Antagonists
Mineralocorticoid receptor antagonists like spironolactone have a rich history dating back to the 15th century Italian discoveries of adrenal glands. The journey of understanding aldosterone's effects on sodium and potassium regulation led to the development of spironolactone, a drug that blocks aldosterone receptors. Notably, aldosterone stimulates sodium reabsorption through ENaC channels and potassium secretion, which spironolactone counteracts by blocking these channels. The delayed onset of action compared to traditional diuretics is due to spironolactone acting within cells, affecting RNA synthesis.
Clinical Usage and Side Effects of Spironolactone
Spironolactone, initially used for liver failure, found a resurgence as a cardioprotective agent following the 'RALES' trial. Its selective inhibition of aldosterone action has led to diverse applications, such as treating hyperaldosteronism, heart failure, and even acne. Commonly prescribed, spironolactone's delayed effect entails considerations for dosing, balancing efficacy with potential side effects like hyperkalemia and metabolic alkalosis, particularly in patients with preserved kidney function. Striking the right balance in cirrhosis treatment remains a nuanced practice.
Interaction with Other Diuretics and Unique Mechanism of Action
Combining spironolactone with other diuretics such as loops, thiazides, or SGLT2 inhibitors provides comprehensive nephron blockade in managing conditions like heart failure or cirrhosis. Spironolactone's unparalleled mechanism of action, impacting RNA synthesis and sodium channels within cells, sets it apart from traditional diuretics that act primarily at the luminal level. Its long-acting nature warrants caution in managing potential side effects, underscoring the need for individualized dosing strategies.
Exploration of the Genetic Condition Geller Syndrome
Geller syndrome, an exceedingly rare autosomal dominant disorder, showcases a gain-of-function mutation in aldosterone receptors, leading to hypertension, especially during pregnancy. Women with Geller syndrome often experience increased blood pressure due to the altered receptor function. Notably, in Geller syndrome, spironolactone, typically an antagonist, transforms into an agonist, emphasizing the complexity and unique genetic manifestations in regulating blood pressure and sodium balance.
Relevance of Spirinolactone in Transgender Care
Spironolactone is utilized by transgender individuals for hair and breast modifications due to its anti-androgen properties. In cases where excessive spironolactone leads to volume depletion and hypotension, the consumption of licorice is suggested to counteract such effects and maintain mineralocorticoid balance.
Milleride's Impact on Sodium Channel Inhibition
Milleride's discovery in the 1960s led to its role in blocking epithelial sodium channels, notably studied in toad bladder models. Beyond its effect on sodium channels, milleride exerts an influence on various sodium and cation transporters, showcasing potential antibiotic properties against certain bacterial infections.
Tovaptan's Significance in Treating Medical Conditions
Tovaptan, primarily known for its diuretic properties, gained prominence for mitigating conditions like SIADH and heart failure. However, its extensive usage in diverse applications gradually declined following studies examining its efficacy, particularly in preventing acute kidney injury and managing contrast-induced nephropathy.
The Channelers went where no nephrology podcasters have gone before, recording in front of a live audience at the National Kidney Foundation Clinical Meeting in Austin. We had all eight Channelers doing a live podcast.
We did a Freely Filtered-inspired draft of the best diuretics.
The draft order:
Leticia Rolon
Anna Gaddy
Joel Topf
Roger Rodby
Josh Waitzman
Amy Yau
JC Velez
And Melanie Hoenig
References
JC
Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease
Tolvaptan, a Selective Oral Vasopressin V2-Receptor Antagonist, for Hyponatremia
Josh
Review on amiloride development https://pubmed.ncbi.nlm.nih.gov/7039345/
Toad bladder: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1351665/
Amiloride derivatives that inhibit flagella: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544414/
Amiloride as taste sensor: https://www.science.org/doi/10.1126/science.6691151
Amiloride + ddavp for DI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518801/
Amy
Acetazolamide reversibly inhibits water conduction by aquaporin-4
Inhibition of Human Aquaporin-1 Water Channel Activity by Carbonic Anhydrase Inhibitors
Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus
Acetazolamide in Lithium-Induced Nephrogenic Diabetes Insipidus
In Vivo Antibacterial Activity of Acetazolamide
Roger
50th anniversary of aldosterone
Joel
Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure
Empagliflozin and Heart failure: Diuretic and Cardiorenal Effects
Anna
Clinical Results of Treatment of Diabetes Insipidus with Drugs of the Chlorothiazide Series
Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride
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