Diuretics

Question 1

loop diuretic effects on acid/base

Answer 1

thiazide and loop diuretics induce metabolic alkalosis in three ways: 1. hypovolemia -> incr Na reabs in PT via Na-H exchanger due to incr AgII (leading to more bicarb reabs), 2. hypovolemia -> hyperaldo -> three mechs -> alkalosis, 3. these diuretics cause more Na in distal tubule, where Na enters principal cell and causes negative lumen V which incr H+/K+ secr

Question 2

thiazide diuretic effects on acid/base

Answer 2

thiazide and loop diuretics induce metabolic alkalosis in three ways: 1. hypovolemia -> incr Na reabs in PT via Na-H exchanger due to incr AgII (leading to more bicarb reabs), 2. hypovolemia -> hyperaldo -> three mechs -> alkalosis, 3. these diuretics cause more Na in distal tubule, where Na enters principal cell and causes negative lumen V which incr H+/K+ secr

Question 3

osmotic diuretic effects on acid/base

Answer 3

osmotic diuretics induce metabolic acidosis (bicarb excreted via solvent drag?)

Question 4

CA inhibitor effects on acid/base

Answer 4

CA inhibitors induce metabolic acidosis (more bicarb excretion)

Question 5

K-sparing diuretics effects on acid/base

Answer 5

K-sparing diuretics induce metabolic acidosis (Na not reabsorbed, therefore lumen not negative, therefore H+ not excreted)

Question 6

effects on acid-base by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics

Answer 6

thiazide and loop diuretics induce metabolic alkalosis in three ways: 1. hypovolemia -> incr Na reabs in PT via Na-H exchanger due to incr AgII (leading to more bicarb reabs), 2. hypovolemia -> hyperaldo -> three mechs -> alkalosis, 3. these diuretics cause more Na in distal tubule, where Na enters principal cell and causes negative lumen V which incr H+/K+ secr; CA inhibitors induce metabolic acidosis (more bicarb excretion); osmotic diuretics induce metabolic acidosis (bicarb excreted via solvent drag?); K-sparing diuretics induce metabolic acidosis (Na not reabsorbed, therefore lumen not negative, therefore H+ not excreted)

Question 7

loop diuretic effects on K

Answer 7

loop/thiazide diuretic cause V depletion (-> aldo) and incr distal Na delivery (inhibit TAL/DCT Na reabs) -> incr K secretion -> hypokalemia; also cause alkalosis -> hypokalemia; thiazide are more kaliuretic than loop b/c they have longer DOA and thus less likely to have K conserving time periods

Question 8

thiazide diuretic effects on K

Answer 8

loop/thiazide diuretic cause V depletion (-> aldo) and incr distal Na delivery (inhibit TAL/DCT Na reabs) -> incr K secretion -> hypokalemia; also cause alkalosis -> hypokalemia; thiazide are more kaliuretic than loop b/c they have longer DOA and thus less likely to have K conserving time periods

Question 9

osmotic diuretic effects on K

Answer 9

osmotic diuretics cause V depletion and incr distal NaCl delivery -> hypokalemia

Question 10

Ca inhibitor effects on K

Answer 10

acetazolamide causes V depletion (-> aldo) and incr distal Na delivery (w/ NaHCO3) and poorly resorbable anion (HCO3-) delivery -> hypokalemia

Question 11

mannitol

Answer 11

osmotic diuresis

Question 12

acetazolamide

Answer 12

CA inhibitors

Question 13

furosemide

Answer 13

inhibits NKCC2 by substituting for chloride on transporter

Question 14

how do most diuretics get into tubule?

Answer 14

most via tubular secretion rather than glomerular filtration (protein-bound)

Question 15

mechs of “braking phenomenon”

Answer 15

neural (SNS), endocrine (RAAS), physical hypertrophy of unaffected nephron segments (chronic diuretic resistance)

Question 16

conditions associated w/ decreased diuretic action (4)

Answer 16

bowel wall edema (no GI abs of drug); hypoalbuminemia (no proteins to bind drugs); ECV depletion (decr RPF); CKD

Question 17

CA inhibitors lost from PT, lost in urine

Answer 17

lost from PT: bicarb, Na (b/c NaH has no gradient so Na not reabs), water; however, Na reabs in distal nephron, so instead lost in urine: bicarb, K (due to distal delivery of NaHCO3)

Question 18

clinical use of CA inhibitors (4)

Answer 18

limited use as natriuretic; correction of metabolic alkalosis (be careful b/c alkalotic pts are already hypokalemic and CA inhibitor will worsen it); altitude sickness; glaucoma

Question 19

loop diuretics lost in urine

Answer 19

chlorine, K, Na, water, Ca, Mg; these diuretics also block uric acid secretion so less uric acid lost; more water than Na lost (hypotonic urine -> can use to correct hyponatremia)

Question 20

clinical use of loop diuretics (4)

Answer 20

correction of edematous disorders (CHF, pulm edema, nephrotic syndrome, renal failure); hyperkalemia; hypercalcemia; severe HTN (rarely used due to short half life)

Question 21

loop vs thiazide half life

Answer 21

thiazide longer half life (better to tx HTN, more likely to cause kaliuresis)

Question 22

loop diuretic side effects (7)

Answer 22

hypokalemia, hypocalcemia, hypercalcuria (stones), hypomagnesemia, hyperuricemia (block uric acid secretion), ototoxicity (usually reversible, worse w/ ethacrynic acid, b/c NKCC also in ear), sulfa allergy (use ethacrynic acid b/c no sulfa group)

Question 23

ethacrynic acid

Answer 23

loop diuretic used for ppl w/ sulfa allergies, has side effect of ototoxicity (so don’t use unless severe sulfa allergy)

Question 24

thiazide diuretics: onset of action timeline, natriuretic effect timeline, potency, effects on ions (Na, Cl, Ca, K, Mg)

Answer 24

onset of action 2-3 hrs, natriuretic effect < 6 hrs; less potent than loop diuretics b/c less Na reabs in DCT: loss of NaCl in urine (through NCC), increased calcium reabs (used to prevent stones and tx hypercalcuria), and loss of K and Mg in urine

Question 25

clinical use of thiazides (4)

Answer 25

1st line therapy in HTN (anti-HTN effects actually continue after braking phenomenon) along w/ low salt diet; combo w/ loop diuretic to prevent braking phenomenon in chronic edematous states (beware of hypokalemia and hypomagnesemia); prevention of stones (1st line therapy due to hypocalcuric effects); tx of hyperkalemia

Question 26

side effects of thiazides (7)

Answer 26

hypokalemia; hypomagnesiumia; hyponatremia; hyperuricemia (block uric acid secretion); incr Ca reabs; carb intolerance (impaired insulin release); sulfa allergy

Question 27

amiloride

Answer 27

blocks ENaC

Question 28

spironolactone

Answer 28

aldo receptor antagonist

Question 29

eplerenone

Answer 29

aldo receptor antagonist

Question 30

clinical uses of K sparing diuretics (4)

Answer 30

not very good natriuretics, but used w/ other diuretics to prevent hypokalemia; spironolactone doesn't req tubular secretion and so works well at low EABV -> use to improve survival in CHF, cirrhosis, and for its anti-proteinuric effects (anti RAAS)

Question 31

side effects of K sparing diuretics (2)

Answer 31

hyperkalemia in pts prone to it (CKD, CHF -> balance w/ loop diuretic in these pts); painful gynecomastia w/ spironolactone

Question 32

osmotic diuretics (4)

Answer 32

mannitol, radiocontrast dye, glucose (in hyperglycemia), urea (after relief from obstructive uropathy or high-protein tube feedings)

Question 33

osmotic diuretics clinical uses (2)

Answer 33

lead to Na and water losses, but lose more water than Na (hypotonic fluid loss) -> can lead to hyperosmolarity of blood (use to tx incr intracranial P due to hypotonicity); exogenous osmotic agents act as volume expanders in vasculature -> don't use in edematous states, but good for dialysis pts who are hypotensive

Question 34

how is Na loss w/ osmotic diuretics?

Answer 34

Na abs but water is not due to effective osmole (like mannitol) in tubule, thus as Na is absorbed more than water, [Na] in tubule decreases so that there is no concentration gradient remaining to drive reabsorption; so while Na and water are thus both lost in urine, there is still more water lost than sodium -> leads to hypertonicity of blood

Question 35

Na excretion (as % of filtered load) for: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics

Answer 35

osmotic: 10%, CAI: 5-10%, loop: 25%, thiazide: 5-10%, K-sparing: 3-5%

Question 36

effects on Ca excretion by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics

Answer 36

osmotic diuretics incr Ca excretion (solvent drag); CAI incr Ca excretion (solvent drag) - incr calciuresis along w/ alkaline urine = stones; loop diuretics incr Ca excretion (no positive lumen to push reabs of Ca) -> can cause stones; thiazide diuretics decr Ca excretion -> tx stones; K sparing diuretics don't affect Ca excretion

Question 37

effects on free water excretion by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics

Answer 37

osmotic diuretics and CAI incr water excretion (incr NaCl delivery to DCT allows increased dilution); loop and thiazide diuretics decr water excretion b/c can't dilute w/ NCC and NK2Cl blocked; K sparing diuretics don't affect dilution ability

Question 38

effects on free water reabs by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics

Answer 38

osmotic diuretics and CAI incr water reabs; loop diuretics decr water reabs (can't concentrate b/c gradient is dissipated); thiazide and K sparing diuretics don't affect water reabs