Pharmacology of Diuretics

Question 1

Carbonic Anhydrase Inhibitors

Answer 1

• Predate all other diuretics
• Act in the proximal tubule
• Prototype: Acetazolamide
• Inhibits carbonic anhydrase (CA) that facilitates the reabsorption of NA and HCO3

Carbonic Anydrase Inhibitors
- Indications
- CAI have limited utility as diuretics
o They work too early in the nephron to induce a clinically significant diuresis
o Potential for causing metabolic acidosis
- Side effects:
o Metabolic Acidosis
o Renal Stones (alkaline urine leads to precipitation and stone formation)
Hypokalemia

Question 2

Acetazolamide

Answer 2

Carbonic Anhydrase Inhibitors

Question 3

Loop Diuretics

Answer 3

• Site of TAL of Henle
• High-celing
• Prototype: Furosemide
• Mechanism:
  o Inhibit NA/K/2CL contransporter
  o Reduces the amount of NA+ reabsorbed at this site

Loop Diuretics:
- Indications:
o Edema
o HT

Side Effects: 
-	Hypokalemia
-	Metabolic Alkalosis 
-	Hyperuricemia 
o	Can form crystals in joints (gout)
Competes with the excretion of uric acid

Question 4

Furosemide

Answer 4

Loop Diuretics

Question 5

Thiazide Diuretics

Answer 5

• Site: distal tubule
• Most commonly prescribed diuretics
• Prototype: Hydrochlorothiazide
• Mechanism:
  o Inhibit the Na/CL transporter
  o Note at this point in the nephron most of the Na+ absorption has already occured

-	Indications
o	HT (diuresis, vasodilation reduces TPR)
o	Edema
o	Nephrogenic Diabetes Insipidus 
-	Side effects: 
o	Hypokalemia
o	Metabolic alkalosis
o	Hyperuricemia
o	Hyperlipidemia (total increase in cholesterol and LDL)
o	Hyperglycemia

Question 6

Hydrochlorothiazide

Answer 6

Thiazide Diuretics

Question 7

Potassium-Sparing

Answer 7

• Site: late distal tubule/early corticol collecting duct (CCD)
• Act very late in the nephron, so minimal natriuresis/diuresis

o Upregulates Na/K exchange pump on basal membrane of principal cells
o Upregulates epithelial sodium channels
o Stimulates H/K exchange in the intercalated cells of cortical collecting tubules

Mineralocorticoid (aldosterone) receptor antagonist
- Prototype: Spironolactone
ENaC Blockers
- Prototypes: Triameterene & Amiloride

-	Indicatoins: 
o	HT
o	Heart Failure 
-	Side effects: 
o	Hyperkalemia
o	Spironolactone: antagonism of androgen or progesterone receptors
♣	Gynecomastia
♣	Dysenorrhea 
♣	Note there is an alternative here, eplerenone
Osmotic Diuretics

Question 8

Spironolactone

Answer 8

Mineralocorticoid (aldosterone) receptor antagonist

Question 9

Triameterene & Amiloride

Answer 9

ENaC Blockers

Question 10

Osmotic Diuretics

Answer 10

• Prototype: mannitol
• Osmotic diuretics are freely filtered but poorly reabsorbed
• Stay in the tubule, pulling water into the tubule and promoting diuresis
• Limited utility as diuretics
• Mainly used for non-diuretic indications
• Increased intracranial pressure (ICP)

Question 11

mannitol

Answer 11

Osmotic Diuretics