Lecture 11: Diuretics Flashcards
Renal Vasodilators
Examples: Dopamine, Fenoldopam, Caffiene, Atriopeptins
Mechanism: Selectively dilates renal vasculature that modifies proximal tubular function. Increases RBF with no change to GFR, decreasing filtration fraction, resulting in decreased proximal tubular sodium reabsorption which is compensated by more distal nephron segments limiting diuretic effect
Therapeutic uses: Limited, hypertensive crisis and shock
Osmotic Diuretics
Examples: Mannitol
Mechanism: (1. Freely filtered. 2. Not reabsorbed. 3. Metabolically inert)
Given IV, act in tubular lumen as nonreabsorbable solute, Urine volume and Na+ excretion are proportional to osmotic load. Thus increased urinary excretion of sodium, potassium, chloride, water, and mannitol.
Therapeutic uses: Edema, glaucoma, acute renal failure
SE: Related to volume overload and expansion of intravascular fluid volume. Also a rare hypersensitivity
Inhibitors of carbonic anhydrase
Examples: Acetazolamide
Mechanism:
Weak diuretic
Inhibited by acidosis-limits clinical use
Filtered and secreted by Organic Acid Transporter, acts from tubular lumen
Inhibits Carbonic anhydrase in the proximal distal tubule (which normally provides H+ ions for bicarbonate reabsorption)
Increases excretion of Na+, K+, bicarbonate, H2O
Alkalinize the urine
Therapeutic uses: Glaucoma Alkalize the urine for decreasing drug toxicity Altitude sickness Anticonvulsant
SE: Metabolic acidosis and Hypokalemia
Loop diuretics
Examples: Furosemide, Bumetanide, Etharynic acid
Mechanism:
High efficacy (20-30%)
Rapid in onset and short duration of action (20 min)
Na+ K+ 2Cl- Symport inhibitors
Filtered and secreted by the OAT
Acts on the cortical and medullary segments of the ascending limb of the loop of Henle
Increase the excretion of sodium, potassium, chloride, and water
Increases the renal blood flow and GFR
Enhances calcium excretion
Large urine volume
Therapeutic uses:
Edema of cardiac, hepatic, or renal origin,
Acute pulmonary edema
Hypertension
SE: Hypokalemia Alkalosis Hypovolemia Hyperuricemia Hyperglycemia (furosemide only) Ototoxicity
Thiazide diuretics
Examples: Chlorothiazide, Hydrochlorothiazide, Metolazone
Mechanism: Intermediate efficacy Moderate onset (60 min) Long duration Filtered and secreted by the OAT Inhibits Na-Cl symporter Acts on cortical segment of distal tubule Increases excretion of Na+ K+ Cl- H2O Urine is hypertonic-unable to dilute Increases K= secretion Enhances urate reabsorption (PT)
Therapeutic uses:
Edema due to CHF
Hypertension
Hypercalcinuria/Ca salt-renal caliculi
SE: Hypokalemia Alkalosis Hyperuricemia Hyperglycemia Decrease in GFR
Potassium sparing diuretics
Examples:
Spironolactone, Eplerenone (Aldosterone antagonists): Block aldosterone action on collecting duct
Triamterene, Amiloride (Na+ channel inhibitors): Block Na+ entry into principal cells of the collecting duct
Mechanism: Low efficacy Weak diuretic Increases Na+ excretion without K+ loss Increase Na+ excretion Decrease K+ excretion Increase urinary excretion of sodium, chloride, and H2O
Therapeutic uses:
Edema
Hypertension
Seldom used alone but with thiazide or loop diuretics to enhance naturesis without potassium loss
Aldosterone antagonism improves survival in heart failure
SE:
Low efficacy
Hyperkalemia if used alone, thus usually used with thiazide
Gynecomastia (spironolactone»eplerenone)
Triamterene decreases RBF and GFR
Na+ channel inhibitors-mild azotemia
What does ceiling diuretic dose depend on
Diuretic used and Disease
Importance of compartmentalization
Urine<–slow– Body (peritoneal/pleural)
Depending on location of edema, you may need to use slow or fast diuretic
Electrolyte imbalance
- K+ loss parallels Na+ loss
- Use K+ supplement or K+ sparing diuretics
- Hyperkalemia can be fatal
- Hypokalemia rarely life-threatening
Importance of diuretic to chronic heart failure
- Mainstay of heart failure management
- Reduce fluid volume and ventricular preload
- Reduction in heart size and mproves efficiency
- Reduce edema and its symptoms
- BUT NOT ASSOCIATED WITH REDUCTION IN MORTALITY
Importance of Aldosterone antagonist to CHF
Aldosterone antagonist IMPROVES SURVIVAL
- Weak diuretics-small effect on preload
- Reduce potassium loss and hypokalemia and enhance the natriuresis due to other diuretics
- Block cardiac effects of aldosterone: decrease fibrosis and hypertrophy and arrhythmias
In other words:
A. Improve mortality rates and reduce symptoms (even in presence of an ACE inhibitor)
B. Reduce edema, antiarrhthmic, and decrease fibrosis in the myocardium and vessels (ie counteracts adverse remodeling)
How do diuretics decrease edema
- Increase salt and water excretion by reducing renal tubular sodium and water reabsorption
1. Decrease intravascular volume
2. Reduce ECF and edema
