Diuretics Flashcards
What are diuretics used for?
The treatment of water disturbances (e.g. Edema) and/or solute excess, with major focus on sodium
What is the primary effect of diuretics?
Exert effects on parts of the nephron to block the reabsorption of sodium and water and promote urine excretion; also increase rate of natriuresis and Cl excretion to reduce ECF volume
Where is the area of the nephron that reabsorbs 50-60% of the filtered Na and H2O?
Proximal tubule
How much filtered sodium is reabsorbed in the ascending loop of Henle?
25-30%
What part of the nephron is impermeable to sodium but permeable to water?
Thin descending loop of Henle
Where is approximately 5-8% of filtered sodium reabsorbed in the nephron?
Early distal convoluted tubule
Where does the least amount of sodium reabsorption occur in the nephron?
The terminal portion of the distal convoluted tubule and collecting duct
Why do proximally acting diuretics not induce a relatively large loss of sodium and water?
Since almost all the excess fluid delivered out of the proximal tubule can be reabsorbed more distally (mostly ascending loop of Henle/distal tubule)
The rate of urine excretion (diuresis) in a normal animal is directly dependent on what?
The stimulation or inhibition of ADH and by thirst
Incr water intake = decr ADH/thirst, incr diuresis
What are two other pathologic or iatrogenic mechanisms that result in increased diuresis?
- Pressure natriuresis: hypervolemia/hypertension
- Osmotic diuresis: abnormally high concen of active solutes lead to passive diuresis
All diuretics except which one exert their effects on the luminal side of the nephron?
Spironolactone
Which diuretic agent is the only one freely filtered from the blood?
Mannitol
All diuretics (except spironolactone and mannitol) are tightly/loosely protein bound and undergo little/extensive filtration?
Tightly; little
How do the majority of diuretics reach the urine?
By active secretion across the proximal tubule via organic acid or base secretory pathways
What factors reduce diuretic effectiveness?
Decreased renal blood flow or renal disease
Osmotic diuretics
- Agents: Mannitol
- Freely filtered and not reabsorbed, undergoes limited metabolism
- Site of action: all segments (mostly proximal tubule and LOH)
- MOA: hyperosmolality creates water shift, impairs passive H2O reabsorption = causes Na, H2O, Cl, bicarb excretion
- Uses: cerebral edema, increased ICP
- AE: contraindicated in cases of CHF
- Renal protective?
Loop Diuretics
- Agents: Furosemide (lasix)
- MOI: bind and inhibit the Na-K-2Cl cotransporter on the apical membrane of the thick ascending LOH’s loop; excretion of Na, Ca, K, and Mg
- Calciuretic
- Uses: mobilize edema fluid associated w/ cardiac, renal, and hepatic dysfunction, hypercalcemia, CHF, pulmonary edema
- AE: peripheral vasodilation and reduced venous return, hypokalemia, increase in venous capacitance and renin secretion (use w/ ACE inhibitor!)
- *create greater urine volume and less Na loss than other heart failure tx
Thiazide Diuretics
- Agents: Hydrochlorothiazide
- Weak diuretic (less Na absorbed here); GFR and Na delivery-dependent, less effective w/ renal insufficiency
- Site of Action: distal convoluted tubule
- MOI: block NaCl symporter
- Uses: used in combo w/ loop diuretic to treat refractory heart failure, long-term prevention of calcium-containing uroliths
- Anticalciuretic
Aldosterone Antagonists
- Agent: Spironolactone (poor diuretic)
- Site of Action: late distal tubule and collecting duct
-
MOA: binds aldosterone receptor on the late distal tubule and collecting duct to i_ncr Na, Ca, H2O excretion_ and diminishes degree of K loss
- relatively weak natriuretic activity
- Typically used in combo w/ loop or thiazide diuretic
- Uses: primary hyperaldosteronism (adrenal tumors/hyperplasia), cirrhosis, CHF
- SE: hyperkalemia and skin changes
Carbonic Anhydrase Inhibitors
Agents: Acetazolamide (weak diuretic)
Site of action: proximal tubule
MOA: binds non-competitively to CA enzyme
Uses: elevated intraocular pressure in glaucoma
SE: hyperchloremic metabolic acidosis
Potassium-Sparing Diuretics
- Agents: Amiloride and Triamterene (weak diuretics)
- Site of Action: Late distal tubule and collecting duct
- MOA: inhibit electrogenic Na reabsorption, suppressing driving force for K secretion; inhibits aldosterone actions
- Uses: in conjunction w/ proximal diuretics; lithium toxicity
- SE: hyperkalemia (Amiloride), nephrotoxicity, crystalluria and cast formation, stones, acute renal failure (Triamterene)
Vasopressin Receptor Antagonists (Aquaretics/Vaptans)
Site of action: V2 ADH receptors
MOA: inhibit action of vasopressin in kidney and promote solute-free water clearance
Uses: free water retention in hypervolemic hyponatremia (e.g. Heart/liver failure), or normovolemic hyponatremia (inappropriate ADH secretion)
Not used in small animals (Vaptans)
Most diuretics are ________ and require __________ by the proximal tubule into the urine
Highly protein bound; active transport/secretion
