Diuretics

Question 1

Loop Diuretics - Mechanism

Answer 1

Acting on the ascending limb of the Loop of Henle to inhibit NaCl transport; more Na+, K+, and Cl- is retained in the urine

Question 2

Loop Diuretics - Pharmacokinetics

Answer 2

Rapid oral absorption, excreted by renal filtration; duration of effect is 2-3 hours (Furosemide)

Question 3

Loop Diuretics - Prototypical

Answer 3

Furosemide

Question 4

Clinical usages of diuretics

Answer 4

Heart failure patients with volume overload; Furosemide is first line; bumetanide and tosemide for refractory congestion

Question 5

Loop Diuretics - Adverse Effects

Answer 5

Hypokalemic metabolic alkalosis due to enhanced secretion of K+ and H+
Ototoxicity
Hyperuricemia
Hypomagnesemia

Question 6

Thiazides - Mechanism

Answer 6

Act on the convoluted tubule to inhibit the NaCl transporter; increases urinary excretion of NaCl with modest diuretic effect

Question 7

Hydrochlorothiazide - Pharmacokinetics

Answer 7

Oral absorption, secreted by organic acid secretory system

Question 8

Hydrochlorothiazide - Adverse Reactions

Answer 8

Hypokalemia
Hyperuricemia
Impaired carbohydrate tolerance (hyperglycemia, glucosuria) and hyperlipidemia

Question 9

Mechanism of coupling Na+ reabsorption with K+ excretion

Answer 9

In the collecting tubule the driving force for Na+ into the cell exceeds that for K+ exit; Na+ enters the cell and the lumen becomes electronegative, driving Cl- into cells and K+ into the urine

Question 10

Aldosterone Antagonists - Example

Answer 10

Spironolactone

Question 11

Spironolactone - Mechanism

Answer 11

Competitively inhibits the aldosterone receptor, preventing the effect of the aldosterone TF to increase the number and activity of Na+ and K+ membrane channels; blockade of the aldosterone effect means that less Na+ is reabsorbed from the collecting duct, the lumen potential becomes positive, and less K+ moves into the urine

Question 12

Uses of Spironolactone

Answer 12

Added to therapy for LVEF < 30% on ACEI/ARB and B-blocker therapy

Adds additional diuresis plus antiremodeling effect

Monitor serum K+ and GFR

Question 13

Spironolactone - Adverse Effects

Answer 13

Hyperkalemia, arrhythmias
Endocrine abnormalities (gynecomastia via secondary blockage of androgen receptor)

Question 14

K+ sparing diuretics - 3 examples

Answer 14

Spironolactone
Amiloride
Triamterene

Question 15

Amiloride & Triamterene

Answer 15

Class of K+ sparing diuretics that work by blocking Na+ channels on collecting duct lumen to decrease Na+ reabsorption and thus decrease coupled K+ secretion