Diuretics and RAAS Antagonists

Question 1

Site and mechanism of action of loop diuretics

Answer 1

lumenal (urine) surface of the renal tubule cells

• inhibits NaCl transport (NaClX) at the thick ascending limb
• associated with an increase in Mg2+, Ca2+ excretion
• inc renal blood flow
• patients with HF have reduced diuretic response -> dec drug delivery to kidney -> hypoperfusion activates RAAS and SNS

Question 2

Loop diuretic role in the tx of HF

Answer 2

Furosemide is most common used. Used in HF pts with volume overload to eliminate the sx of fluid retention (higher efficacy with salt restriction). If Furosemide is not effective, use Torsemide or Bumetanide

Question 3

Adverse effects of loop diuretics

Answer 3

• Hypokalemic metabolic alkalosis via enhanced K+ and H+ excretion
• hyperuricemia (can lead to a gout attack)

Question 4

thiazide site and MOA

Answer 4

lumenal (urine) surface of the renal tubule cells

• Inhibit the Na+/Cl- cotransporter (inc urinary excretion of NaCl) at the distal convoluted tubule
• modest diuretic effect
• increases reabsorption of Ca2+

Question 5

thiazide role in tx of HF

Answer 5

used for mild HF, higher doses needed than in HTN and more efficacious diuretics are usually required

Question 6

thiazide adverse effects

Answer 6

• competition with uric acid secretion may precipitate a gout attack
• hypokalemia -> predisposition to ectopic pacemakers
• hyperglycemia
• hyperuricemia
• allergic rxns: related to sulfonamide structure

Question 7

site and MOA of aldosterone antagonists

Answer 7

• collecting tubule
• mild diuresis
• decrease K+ excretion
• Competitive antagonist at aldosterone receptor -> blocks synthesis of NaK channels-NaK ATPase

Question 8

aldosterone antagonsist role in tx of HF

Answer 8

Spironolactone is first choice: block of aldosterone receptors on heart – acting as RAAS antagonist rather than diuretic

• anti-remodeling action (hypertrophy and dilation)
• benefit from raising serum K+
• added to tx for LVEF <30-35%.

Question 9

K+ sparing diuretic adverse efffects

Answer 9

• Hyperkalemia -> EKG changes, conduction abnlities, arrhythmias
• Risk inc by: inc age, underlying renal dysfunction, higher doses, combined use of ACEI or ARB, use of NSAID analgesics
• Endocrine abnlities via block of androgen receptor (Spiro only)

Question 10

Na+ channel blockers site and MOA

Answer 10

• collecting tubule
• mild diuresis
• decrease K+ excretion
• direct effect to block the Na+ channels on collecting duct lumen and dec Na+ reabsorption

Question 11

Na+ channel blockers role in tx of HF

Answer 11

NO utility in HF