Diuretics

Question 1

Proximal Tubule important for reabsorption of

Answer 1

Na-HCO3

NaCl

H2O

as well as AA’s, glucose, etc.

Question 2

Where are the two main sites of K reabsorption?

Answer 2

Proximal convoluated tubule (65%) - compulsory

Distal convoluted tubule - regulated

Question 3

Carbonic Anhydrase Inhibitors used for?

Answer 3

Used to be diuretic but now more for metabolic

Question 4

Carbonic Anhydrase Inhibitors MOA

Answer 4

inhibit CA

decreased HCO3- reasorption in PCT

decreased HCO3- formation in kidney/RBC’s

Inhibition of titratable acid and NH4+ secretion

Ultimately leads to increased HCO3- excretion which pulls NaCl and H2O with it resulting in DIURESIS

Question 5

Clinical indication of Carbonic anhydrase inhibitors

Answer 5

Glaucoma
Acute mountain sickness
Induce urinary alkalinization
Edema (combined with NKCC and NCC inhibitors)

Question 6

Adverse Effects of Carbonic Anhydrase Inhibitors

Contraindicated in?

Answer 6

hyperchloremia metabolic acidosis

renal stones

renal loss of K

Cirrhosis (d/t increased NH4)

Question 7

Osmotic Diuretic MOA

Main site of action?

Answer 7

freely filtered/poorly reabsobred

Increases tubular osmotic pressure = pulling water into tubule and keeping it there

Thin loop of Henle

Question 8

Clinical Applications of Osmotic Diuretics (4)

Answer 8

Prophylaxis of acute renal failure

Cerebral edema

Dialysis dysequilibrium syndrome

Acute glaucoma attacks

Question 9

Adverse effects of osmotic diuretics

Answer 9

ECV expansion - risk of pulmonary edema w/CHF

Hyponatremia/hypernatremia

Question 10

Contraindications of Osmotic Diuretics

Answer 10

anuria - d/t kidney disease

impaired liver function

active cranial bleed

Question 11

Osmotic Diuretics

Answer 11

MANNITOL
glycerin
isosorbide
urea

Question 12

Carboinic ANhydrase Inhibitors

Answer 12

ACETAZOLAMIDE
dichlrophenamide
methazolamide

Question 13

Loop Diuretics (NKCC Inhibitors)

Answer 13

FUROSEMIDE
bumetanide
ethacrynic acid

Question 14

NKCC Inhibitors MOA

Answer 14

inhibit Na/K/2Cl cotransporter

inhibits reabsorption of solute from Thick Ascending Limb

Venodilation occurs - decreases RA and PCW pressures within minutes

Increase fractional Ca and Mg excretion - both through paracellular route

Question 15

Clinical Indications of NKCC Inhibitors

Answer 15

Pulmonary edema

CHF

Acute Renal Failure

Hypercalcemia - (saline + loop diuretics)

Question 16

MAJOR adverse effect of NKCC Inhibitors

Answer 16

HYPOKALEMIA

used extensively in CHF patients along with digoxin and other potassium sensitive drugs

Question 17

NCC Inhibitors (Thiazides and Sulfonamides)

Answer 17

CHLORTHALIDONE
hydrochlorothiazide
metolazone
indapamide

Question 18

NCC inhibitors MOA

Answer 18

Inhibit Distal convoluted tubule Na/Cl co-transporter

Decreases Ca excretion

Causes vasorelaxation

Question 19

Clinical Applications of NCC INhibitors (thiazides/sulfonamides)

Answer 19

Hypertension

Edema control

Hypercalciuria

Nephrolithiasis

Nephrogenic diabetes insipidus

Question 20

Inhibitors of renal epithelial Na channels

Answer 20

AMILORIDE

triamterene

Question 21

Renal Epithelial Na Channel Inhibitors MOA

Answer 21

block Na channels in late distal convoluted tubule and cortical collecting ducts

causes MODEST natriuresis and prevention of K LOSS

Question 22

Clinical indications of Renal Epithelial Na Channel Inhibitors

Answer 22

K-sparing agents in HYPOKALEMIC ALKALOSIS

in combo with thiazides/sulfonamides

Question 23

Aldosterone receptor antagonists

Answer 23

SPIRONOLACTONE

eplerenone

Question 24

Aldosterone antagonist MOA

Answer 24

antagonize aldosterone receptor

decrease Na reabsorption - natriuresis

decrease loss of K in exchange for Na

Question 25

Spironolactone Therapeutic Effects (4)

Answer 25

Prevention of LV remodeling and cardiac fibrosis Prevention of sudden cardiac death Hemodynamic effects Vascular effects - decreased NADPH oxidase actiity

Question 26

Clinical Applications of Spironolactone

Answer 26

Edema/Hypertension Standard therapy of heart failure Primary hyperaldosteronism Refractory edema associated with secondary hyperaldosteronism

Question 27

Adverse Effects of Spironolactone

Answer 27

HYPERKALEMIA metabolic acidosis Effects d/t binding to other steroid receptors (gynecomastia, impotence, hirsutism)