Pharm: Diuretics

Question 1

Major function of Principle Cells and intercalated cells in the nephron.

Answer 1

Principle: regulates sodium content. reabsorbs sodium and secretes potassium.

Intercalated: controls pH. secretes protons

Question 2

Amiloride

Answer 2

Potassium Sparing
MOA: secreted from Organic BASE transporters in S2 portion of proximal tubule and inhibit Epithelial Sodium Channels (ENaC) on the luminal side of principle cells.

Indications: Liddle Syndrome (overactive ENaC mutation), Lithium-induced nephrogenic diabetes insipidus

Adverse Effects: hyperkalemia, hyperchloremic metabolic acidosis

Question 3

Triamterene

Answer 3

Potassium Sparing
MOA: secreted from Organic BASE transporters in S2 portion of proximal tubule and inhibit Epithelial Sodium Channels (ENaC) on the luminal side of principle cells.

Indications: Liddle Syndrome (overactive ENaC mutation), Lithium-induced nephrogenic diabetes insipidus

Adverse Effects: hyperkalemia, hyperchloremic metabolic acidosis, nephrolithiasis (drug is insoluble in urine)

Question 4

Spironolactone

Answer 4

Potassium Sparing
MOA: binds mineralocorticoid receptors in principle cells preventing aldosterone from binding preventing ENaC synthesis.

Indications: Conn Syndrome (aldosterone secreting adenoma), liver failure and nephrotic syndrome leading to hyperaldosteronism, edema, heart failure, hypertension.

Adverse Effects: hyperkalemia, hyperchloremic metabolic acidosis, gynecomastia and impotence (can bind steroid receptors other than mineralocorticoid)

Question 5

Eplerenone

Answer 5

Potassium Sparing
MOA: binds mineralocorticoid receptors in principle cells preventing aldosterone from binding preventing ENaC synthesis.

Indications: Conn Syndrome (aldosterone secreting adenoma), liver failure and nephrotic syndrome leading to hyperaldosteronism, edema, heart failure, hypertension.

Adverse Effects: hyperkalemia, hyperchloremic metabolic acidosis

Question 6

Furosemide

Answer 6

Loop Diuretic
MOA: secreted by organic ACID transporter in S2 portion of proximal tubule to block NKCC pump in the ascending loop of Henle

Indications: edema (pulmonary, cardiac, vascular), hypercalcemia, acute renal failure (stimulates PG E2 for renal vasodilation)

Adverse Effects: hypokalemic metabolic alkalosis, hyperuricemia (can lead to gout b/c uses same acid transporter), ALLERGIC RXN (sulfonamide group), ototoxicity

Question 7

Ethacrynic Acid

Answer 7

Loop Diuretic
MOA: secreted by organic ACID transporter in S2 portion of proximal tubule to block NKCC pump in the ascending loop of Henle

Indications: edema (pulmonary, cardiac, vascular), hypercalcemia, acute renal failure (stimulates PG E2 for renal vasodilation)

Adverse Effects: hypomagnesemia, hypochloremia, hypokalemic metabolic alkalosis, hyperuricemia (can lead to gout b/c uses same acid transporter), ototoxicity

Question 8

Why don’t patients that take Loop diuretics have hypocalcemia?

Answer 8

Parathryoid hormone allows reabsorption of calcium in the distal convoluted tubule.

Question 9

Hydrochlorothiazide

Answer 9

Thiazide Diuretic
MOA: secreted by organic ACID transporter in S2 portion of proximal tubule to block NaCl pump in distal tubule.

Indication: 1st line for HTN, heart failure, nephrolithiasis of hypercalciuria origin, nephrogenic diabetes insipidus

Adverse Effects: hyeruricemia (may lead to gout), hypokalemia, metabolic alkalosis, hypercalcemia

Question 10

Chlorthalidone

Answer 10

Thiazide Diuretic
MOA: secreted by organic ACID transporter in S2 portion of proximal tubule to block NaCl pump in distal tubule.

Indication: 1st line for HTN, heart failure, nephrolithiasis of hypercalciuria origin, nephrogenic diabetes insipidus

Adverse Effects: hyeruricemia (may lead to gout), hypokalemia, metabolic alkalosis, hypercalcemia

Question 11

How do thiazide diuretics treat kidney stones caused by high calcium secretion and therefore can possibly lead to hypercalcemia?

Answer 11

When the sodium chloride channel is inhibited in the distal tubule, the intracellular concentration of sodium drops in the tubule epithelial cells.

A calcium sodium antiport starts to upregulate to bring sodium into the cell from the blood and send calcium out of the cell into the blood. This drops the intracellular level of calcium. A calcium transporter on the luminal side then is over stimulated and lets a lot of calcium into the cell.