Dieuretics

Question 1

Acetazolamide (Diamox)

Answer 1

Class: Proximal Tubule (Na/H) Diuretics:
Carbonic Anhydrase Inhibitors

MOA: -↓ Generation of H+ to exchange
for Na+
- ↑ excretion of bicarbonate (to the
distal nephron)
- ↑ excretion of K+ due to ↑ delivery
of Na+ and HCO3- to distal
nephron → Causes development of
hyperchloremic metabolic acidosis
(↓ HCO3- in blood)

Adverse effects: Metabolic acidosis
Hypokalemia (due to ↑ excretion of
K+)

Clinical Pearls: NEVER A FIRST LINE DIURETIC (⅔ of Na+ is reabsorbed)
Glaucoma: ↓ rate of aqueous humor formation & ↓ intraocular pressure
Alkalinization of the urine in poisonings
with organic acids (salicylate, phenobarbital)
→ promotes excretion of organic acids
Treatment of metabolic alkalosis →
↓HCO3- level in blood (particularly in
congestive HF)

Question 2

Furosemide (Lasix)
Bumetanide (Bumex)
Torsemide (Demadex)
Ethacrynic Acid (Edecrin)

Answer 2

Drug class: Loop Diuretics

MOA: Inhibits the cotransport of Na+/K+/2Cl- at the luminal membrane of the thick ascending limb of Henle → blocks Na+/K+/2Cl- uptake→ produce a diuresis that is 10-25% of filtered load → MOST
POTENT DIURETICS

How to get to Site of action: loop
diuretics filtered across glomerulus
→ secreted by organic anion
transport system in proximal tubule
→ travels in the lumen to site of
action

Adverse effects: Ototoxicity (when given i.v. @ high dose)
Hypokalemia
Hypomagnesemia
Dehydration
Allergy (sulfa)
Metabolic alkalosis
Nephritis (interstitial)
Gout

Clinical pearls: Ethacrynic Acid (Edecrin): used only with SULFA ALLERGY
-Edema of cardiac (HF), renal or hepatic
organ
-Congestive HF leading to pulmonary
edema
-Hypercalcemia: inhibits calcium
reabsorption in the TAL of loop of Henle (↑
excretion of Ca++)
-Nephrotic syndrome or Hepatic cirrhosis
Requires Renal function to get to site of
action (↓ GFR = higher dose required)

May compete with other organic acids for
secretion (other organic acid present in
system = higher dose required)

Question 3

Hydrochlorothiazide
Chlorothalidone
Metolazone

Answer 3

Drug class: Distal tubule: Thiazide diuretics

MOA: Produce a diuresis that is 5% of
the filtered load (not as potent as
loop diuretics)
Inhibits Na/Cl transporter on
luminal membrane → ↑ calcium
reabsorption in the distal tubule
Adverse effects: 
Hypokalemia
Hyponatremia
HyperGlycemia
HyperLipidemia
HyperUricemia
HyperCalcemia

Clinical Pearls:
Hypertension (more severe HTN:
combination of thiazide with other drugs)
Mild edema
Hypercalciuric kidney stone disease
(Thiazides: Ca++ reabsorption → ↓ loss of
Ca++ in urine → ↓ formation of Ca++ stones)
→ Usually added on to other diuretic
therapies

Chlorthalidone: 2x as potent, longer DOA
Metolazone: can be used in patients w/ low
GFR

Question 4

Spironolactone,

Eplerenone

Answer 4

Drug class: Late distal tubule and collecting ducts:
Potassium
sparing
diuretics
-Aldosterone dependent

MOA: Can produce diuresis 2-3% of
filtered load
Competitive antagonist for
aldosterone receptor → ↓Na+
absorption, ↓K+ secretion
May have delayed effect (upto
48hrs)

Adverse effects: Hyperkalemia (use of other agents which block RAAS increase
likelihood of hyperkalemia)

Spironolactone has steroid like
side effects: gynecomastia in men,
menstrual irregularities in women
(eplerenone has much less side
effects - used when side effects
arise with spironolactone)

Clinical Pearls: Drug of choice for hyperaldosteronism

Spironolactone used for primary and
secondary hyperaldosteronism (such as
congestive HF)

Question 5

Amiloride, Triamterene

Answer 5

Drug class: Late distal tubule and
collecting ducts: Potassium sparing diuretics
-Aldosterone Independent

MOA: Amiloride: acts at luminal surface
to block Na channels, secreted in
proximal tubule as organic cation
(site of action) -RAPID onset
Triamterene: blocks Na channels,
different structural class

Adverse effects: Hyperkalemia (use of other agents which block RAAS increase likelihood of hyperkalemia)

Clinical pearls: Combination therapy to prevent thiazide
diuretic induced hypokalemia
(hydrochlorothiazide/ triamterene =
dyazide)

Question 6

Mannitol

Answer 6

Drug class: Osmotic diuretics
MOA: ↑ urine volume through osmotic
force in kidney tubule
Freely filterable at the glomerulus
and non-reabsorbable particles
enter the tubule lumen
→ this obligates water to stay in
tubule lumen and other
electrolytes are dragged with it
(basically, inhibit reabsorption of
H2O and Na)

Clinical pearls: Must be given intravenously

Question 7

Tolvaptan, Conavaptan

Answer 7

Drug Class: Antidiuretic Hormone (ADH) antagonists (Aquaretics)
MOA: Inhibit effects of ADH on
collecting duct by blocking V1 and
V2 receptors (blocks H2O
absorption)

Essentially cause LESS water
channels to be inserted → not a
loss of salt, but ↓ reabsorption of
water (↑ plasma osmolality)

Tolvaptan: blocks V2 receptor - PO
Conavaptan: blocks V1a and V2
receptor - IV drug

Clinical Pearls: Syndrome of inappropriate antidiuretic hormone secretion (occur in cancers)

Hyponatremia due to congestive HF, liver
cirrhosis