Pharmacology

Question 1

Describe the mechanism of action of Loop Diuretics.

Answer 1

Loop Diuretics competitively (Cl- is natural substrate) inhibit the NKCC2 transporter on the apical/luminal side of the tubular epithelium of the thick ascending limb to prevent filtered sodium resorption.

Question 2

List examples of Loop Diuretics. (4)

Answer 2

Furosemide (Lasix)
Bumetanide (Bumex)
Torsemide
Ethacrynic Acid

Question 3

What are the major side effects of Loop Diuretics? (6)

Answer 3

Volume Depletion
Azotemia
AKI
Hypo: kalemia, magnesemia, & calcemia
Metabolic or Contraction Alkalosis
Ototoxicity (NKCC2)

Question 4

What are the major side effects of Thiazide Diuretics? (6)

Answer 4

Volume Depletion
Azotemia
Acute Kidney Injury (AKI)
Hypokalemia
Metabolic/ Contraction Alkalosis
Hypercalcemia

Question 5

Describe the mechanism of action of Thiazide Diuretics.

Answer 5

Thiazide Diuretics competitively inhibit (Cl- is the natural substrate) the NaCl transporter in the apical/luminal side of the distal convoluted tubule.

This decreases filtered sodium resorption and increases calcium resorption.

Question 6

List examples of Thiazide Diuretics. (4)

Answer 6

Chlorothiazide
Hydrochlorothiazide
Chlorthalidone
Metolazone

Question 7

What are the indications for Loop Diuretics? (3)

Answer 7

HTN
Edema
Hypercalcemia

Question 8

What are the indications for Thiazide Diuretics? (3)

Answer 8

HTN
Hypercalcuria
Diabetes Insepidus

Question 9

Describe the mechanisms of action for the potassium sparing diuretics, spironolactone, amilioride, & triamterene.

Answer 9

Spironolactone - Competitively inhibits mineralocorticoid receptor (MR). This prevents MR from stimulating Na/K ATPase pump and shuttling of ENAC channels to the apical/luminal side of the CD.

Amilioride and Triamterene - Block ENAC channels on the apical/luminal side of the CD

Both decrease sodium resorption and increase POTASSIUM and HYDROGEN resorption (they are “spared” from secretion).

Question 10

What are the indications for potassium sparing diuretics? (3)

Answer 10

Hypokalemia
Metabolic alkalosis
HTN

Question 11

What are the major side effects for potassium sparing diuretics?

Answer 11

Hyperkalemia
Metabolic Acidosis
Nephrotoxicity/AKI (stones/crystals) - Triamterene
Anti-Androgen effects - Spironolactone

Question 12

Spironolactone has an anti-androgen side effect. What are complications of anti-androgen side effects in males and females?

Answer 12

Males - Gynecomastia and Feminization

Females - Menstrual irregularities & Tender breasts

Question 13

What is the mechanism of action of carbonic anhydrase inhibitors?

Answer 13

Inhibtion of carbonic anhydrase at the PROXIMAL TUBULE leading to increased sodium and bicarbonate secretion in the urine.

Question 14

What are major side effects of Carbonic Anhydrase (CA) inhibitors? (4)

Answer 14

Metabolic Acidosis!!!
Parathesias - Tingling in hand
Bone Marrow Depression
Sedation

Question 15

What are indications for Carbonic Anhyrase (CA) inhibitors? (3)

Answer 15

Edema with metabolic alkalosis (Rare)

Extra renal Edema (ie. glaucoma, altitude sickness, epilepsy)

Question 16

What is the mechanism of action of osmotic diuretics?

Answer 16

Freely filtered and non-reabsorbable polysaccharide that increases the osmolality of the tubular lumen at the PROXIMAL TUBULE which prevents water from being resorbed. (osmosis)

Question 17

What is an example of an osmotic diuretic?

Answer 17

Mannitol

Question 18

What are the major side effects of osmotic diuretics?

Answer 18

Hypernatremia - water is lost more than sodium
Increased ECF osmolality –> Decreased cell tonicity and hyponatremia

Pulmonary Edema (especially is HF)

Question 19

What set(s) of diuretics helps limit alkalosis and hypokalemia?

Answer 19

Loop Diuretics + Potassium Sparing Diuretics

Thiazide Diuretics + Potassium Sparing Diuretics

Question 20

What set(s) of diuretics has the most potent diuretic effect? Why?

Answer 20

Loop and Thiazide Diuretics

The DCT (thiazide diuretic target) resorbs 5-10% of filtered sodium and the TAL (Loop Diuretic Target) resorbs 25% of filtered sodium. Blocking these both decrease sodium resorption by about 30-35%.