Diuretics

Question 1

What are diuretics used for?

Answer 1

The treatment of water disturbances (e.g. Edema) and/or solute excess, with major focus on sodium

Question 2

What is the primary effect of diuretics?

Answer 2

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

Question 3

Where is the area of the nephron that reabsorbs 50-60% of the filtered Na and H2O?

Answer 3

Proximal tubule

Question 4

How much filtered sodium is reabsorbed in the ascending loop of Henle?

Answer 4

25-30%

Question 5

What part of the nephron is impermeable to sodium but permeable to water?

Answer 5

Thin descending loop of Henle

Question 6

Where is approximately 5-8% of filtered sodium reabsorbed in the nephron?

Answer 6

Early distal convoluted tubule

Question 7

Where does the least amount of sodium reabsorption occur in the nephron?

Answer 7

The terminal portion of the distal convoluted tubule and collecting duct

Question 8

Why do proximally acting diuretics not induce a relatively large loss of sodium and water?

Answer 8

Since almost all the excess fluid delivered out of the proximal tubule can be reabsorbed more distally (mostly ascending loop of Henle/distal tubule)

Question 9

The rate of urine excretion (diuresis) in a normal animal is directly dependent on what?

Answer 9

The stimulation or inhibition of ADH and by thirst

Incr water intake = decr ADH/thirst, incr diuresis

Question 10

What are two other pathologic or iatrogenic mechanisms that result in increased diuresis?

Answer 10

• Pressure natriuresis: hypervolemia/hypertension
• Osmotic diuresis: abnormally high concen of active solutes lead to passive diuresis

Question 11

All diuretics except which one exert their effects on the luminal side of the nephron?

Answer 11

Spironolactone

Question 12

Which diuretic agent is the only one freely filtered from the blood?

Answer 12

Mannitol

Question 13

All diuretics (except spironolactone and mannitol) are tightly/loosely protein bound and undergo little/extensive filtration?

Answer 13

Tightly; little

Question 14

How do the majority of diuretics reach the urine?

Answer 14

By active secretion across the proximal tubule via organic acid or base secretory pathways

Question 15

What factors reduce diuretic effectiveness?

Answer 15

Decreased renal blood flow or renal disease

Question 16

Osmotic diuretics

Answer 16

• 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?

Question 17

Loop Diuretics

Answer 17

• 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

Question 18

Thiazide Diuretics

Answer 18

• 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

Question 19

Aldosterone Antagonists

Answer 19

• 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

Question 20

Carbonic Anhydrase Inhibitors

Answer 20

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

Question 21

Potassium-Sparing Diuretics

Answer 21

• 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)

Question 22

Vasopressin Receptor Antagonists (Aquaretics/Vaptans)

Answer 22

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)

Question 23

Most diuretics are ________ and require __________ by the proximal tubule into the urine

Answer 23

Highly protein bound; active transport/secretion