Pharm of Diuretics

Question 1

Diuretic definiton

Answer 1

Agent that increases urinary excretion of Na and water

Question 2

2 main ways Na is reabsorbed in PCT

Answer 2

Na symporter (Na and glucose/Cl/amino acid)
Na-H antiporter
The concentration gradient of Na is kept low due to basolateral Na/K ATPase

Question 3

Renal tubular Na and water transport:

Proximal tubule

Answer 3

Permeable to water

2/3 of Na is reabsorbed here (via channels, symporters, antiporters, and carbonic anhydrase)

Question 4

Renal tubular Na and water transport:

Descending limb

Answer 4

Permeable to water

Water moves from tubule to the hyperosmotic renal medulla

Question 5

Renal tubular Na and water transport:

Ascending limb

Answer 5

Impermeable to water
25% of Na is reabsorbed via NKCC symporter
Causes a dilution of the filtrate and increases the medullary osmolality

Question 6

Renal tubular Na and water transport:

Distal tubule

Answer 6

Impermeable to water
5-10% of Na is reabsorbed (Na-Cl symporter)
Further dilutes the filtrate

Question 7

Renal tubular Na and water transport:

Collecting duct

Answer 7

2-5% of Na reabsorbed
Aldosterone: causes Na to be reabsorbed and K/H to be secreted
ADH causes insertion of aquaporin 2 and the concentration of urine

Question 8

2 places in the nephron that are permeable to water

Answer 8

Proximal tubule

Descending limb

Question 9

4 major classes of diuretics

Answer 9

Carbonic anhydrase inhibitors (acetazolamide)
Loop diuretics (furosemide)
Thiazide diuretics (hydrochlorothiazide)
Potassium sparing diuretics (spironolactone, amiloride)

Question 10

Why does blocking carbonic anhydrase cause a diuretic effect?

Answer 10

No carbonic anhydrase means H2CO3 (from bicarb and H) isnt converter to water and CO2
This decreases the intracellular concentration of bicarb and H (because water and CO2 can cross the membrane and reform them)
Less H means less Na/H antiporter activity
More Na, bicarb, and also water is left in filtrate

Question 11

Acetazolamide

Answer 11

Carbonic anhydrase inhibitor at the proximal tubule
Loss of Na and bicarb (causes metabolic acidosis)
Limited use as a diuretic because tolerance develops after 3 days (body starts making more CA)

Question 12

Adverse effects and main uses for acetazolamide

Answer 12

CA inhibitor
Adverse effects: alkaline urine can cause precipitation of calcium phosphate (renal stones)
Uses: acute mountain sickness, open-angle glaucoma

Question 13

Mechanism of action for furosemide

Answer 13

It’s a loop diuretic

1. At ascending loop of Henle, they inhibit NKCC (eliminate the countercurrent multiplier system)
2. At macula densa cells they inhibit the detection of Na concentration
3. Dilate veins (reduce venous pressure)

Question 14

Loop diuretic effect on renin

Answer 14

Furosemide inhibits absorption of Na, K and Cl which stimualtes rennin release

Question 15

3 stimuli for the secretion of renin

Answer 15

Decrease in renal arterial pressure
Decrease in NaCl at macula densa cells (at DCT)
Decrease in blood pressure (increase in sympathetic discharge)

Question 16

Aldosterone causes…

Answer 16

Na renal reabsorption

K and H secretion

Question 17

Loop diuretics effects on ions

Answer 17

Inhibit NKCC (lose those ions)
Loss of K causes loss of lumen positive potential, causes loss of Mg and Ca
Stimulation of renin release and increases aldosterone causes loss of K and H

Question 18

3 conditions where you would use loop diuretics

Answer 18

CHF
Acute pulmonary edema
Peripheral edema

Question 19

Adverse effects of loop diuretics

Answer 19

Hyponatremia, hypovolemia and hypotension from Na loss
Hypokalemia and metabolic alkalosis due to aldosterone secretion
Hyperuricemia (uric acid crystals deposit in joints) from the diuretics competing with uric acid secretion at proximal tubule (need to be secreted at proximal tubule so they can work on luminal LoH)
Ototoxicity (damage of auditory nerves)

Question 20

Mechanism of action of thiazide diuretics

Answer 20

Block Na/Cl symporter at distal tubule (increase Na excretion and decrease blood volume)
Dilation of arterioles (decrease blood pressure)

Question 21

3 main uses for thiazide diuretics

Answer 21

Hypertension (decrease BP from arteriole dilation and decrease in bv)
Edema (decrease bv and decrease venous pressure and capillary filtration)
Nephrogenic diabetes insipidus (reduces max dilution of the filtrate to deal with the excessive excretion of very dilute urine)

Question 22

Adverse effects of thiazide diuretics

Answer 22

Hyponatremia (from prevention of maximal dilution of urine at the DT)
Hypokalemia and metabolic alkalosis (from aldosterone secretion)
Hyperuricemia (thiazides compete with uric acid secretion)
Hyperglycemia (interference with release/action of insulin)

Question 23

Aldosterone activates the mineralcorticoid receptor to cause…

Answer 23

Increases synthesis of Na/K ATPase (high K in cells allows K to flow down its gradient into lumen - loss)
Increased synthesis of luminal Na channel (Na absorption)

Question 24

Spironolactone

Answer 24

K sparing diuretic
Competitive antagonist of aldosterone
Blocks synthesis of mineralcorticoid receptor
Blocks synthesis of luminal Na channels

Question 25

Amiloride

Answer 25

K spring diuretic

Blocks Na flow through luminal Na channels

Question 26

3 uses for K sparing diuretics

Answer 26

Edema
Heart failure
Primary hyperaldosteronism

Question 27

2 adverse effects of K sparing diuretics

Answer 27

Hyperkalemia (esp when used with K supplements)

Reversible gynecomastia with spironolactone