DIURETICS: (know those used to Tx hypertension and HF) •Thiazide diuretics: hydrochlorothiazide •Loop diuretics: furosemide, ethacrynic acid •Potassium-sparing diuretics: spironolactone , eplerenone , amiloride •Osmotic diuretics: mannitol •Carbonic anhydrase inhibitors: acetazolamide MAP renal perfusion urine output (pressure diuresis) salt output (pressure natriuresis) Normal renal function: Davidoff ‘09
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DIURETICS: (know those used to Tx hypertension and HF) Thiazide diuretics: hydrochlorothiazide Loop diuretics: furosemide, ethacrynic acid Potassium-sparing.
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DIURETICS:(know those used to Tx hypertension and HF)
Spironolactone• Competitively binds to aldosterone receptors -
nonselective(mineralocorticoid, androgenic and progesterone receptors)
• Inhibits aldosterone-induced synthesis of pumps
• Slow onset (WHY?), long duration (active metabolites)
• Weak naturiuretic effects, but lowers BP in some patients with mild/moderate hypertension
• Also indicated for hyperaldosteronemia
• Shown to improve morbidity and mortality in patients with end-staged heart failure (Pitt et al., NEJM, 1999)
Side effects include:Men: gynecomastia and erectile dysfunction because of anti-androgenic actionsWomen: menstrual irregularities, hirsutism
Eplerenone
•More specific for aldosterone receptors than spironolactone therefore avoids side effects
(but really expensive)
•Currently approved hypertension and post-MI LV dysfunction
•CYP450 3A4 inhibitors (e.g., erythromycin, verapamil, and grapefruit juice) can elevate blood levels of eplerenone
Aldosterone is also associated with endothelial dysfunction and fibrotic effects in hypertension, HF and atherosclerosis
(mechanism underlying ACE-I cardioprotection???)Cardioprotective effects appear similar to spironolactonehttp://www.jaapa.com/issues/j20040201/articles/0204wcardiomeds.html