Diuretics & RAAS Antagonists (complete) Flashcards
What is the site and MOA at the nephron for loop diuretics?
Loop of Henle (makes sense)
- Inhibits NaCl transport (Na+-K+-2Cl- transporter) in ascending Loop IMPORTANT
- This is where 25-30% of Na+ is reaborbed
- Increase Mg++, Ca++ excretion
- Increase renal blood flow
- Have GREATEST diuretic effect even if renal function is compromised
How are loop diuretics used in the treatment of heart failure?
- use w/ pts w/ volume overload
- effect enhanced w/ Na+ intake restrictions
- to ^ diuresis it’s paired w/ thiazide
Also used in acute pulmonary edema, refractory edema, and hypercalcemia
What are the adverse effects of loop diuretics? Especially consider effects to plasma electrolytes
- Hypokalemic metabolic alkalosis (via enhanced K+ and H+ excretion)
- Hyperuricemia (^ risk to gout)
- Hypomagnesemia
- Hypocalcemia
- Ototoxicity
- Overdose => dizziness, HA, hypotension
What is the most commonly used loop diuretic?
Furosemide
What do you do if furosemide doesn’t work? Think other loop diuretics
- ^ initial dose of furosemide
- Switch to bumetanide or torsemide
- admin via IV
- If sulfa allergy => ethacrynic acid
What is the site and MOA at the nephron for thaizides?
Distal convoluted tubule
- Inhibits Na+/Cl- cotransporter => increased urinary excretion of NaCl
- Modest diuretic effect (only 5-10% Na+ reabsorbed here)
- Increases reabsorption of Ca++
How are thiazides used in the treatment of heart failure?
- High doses needed than in HTN
- More efficacious diuretics usually required
- But can have synergistic diuretic effect w/ loop diuretics => useful in refractory edema
What are the adverse effects of thiazides? Especially consider effects to plasma electrolytes
- Hypokalemia
- Hyperglycemia
- Hyperuricemia (predisposed to gout)
- Hyperlipidemia (not good if pt has HTN)
- Volume contraction => hyperaldosteronism
- Allergies => skin rashes (sulfonamides)
What is a common type of thiazide used?
Hydrochlorothiazide
What is the site and MOA at the nephron for K-sparing diuretics, specifically aldosterone antagonists?
Collecting tubule (2-5% of filtered Na+ reabsorbed here)
- Competitive antagonist at aldosterone receptor
- Blocks synthesis of Na+ and K+ channels, Na+-K+-ATPase
- Mild diuresis => important in determining final urinary [Na+]
How are K-sparing diuretics, specifically aldosterone antagonists, used in the treatment of heart failure?
- Block aldo receptors on heart => RAAS antagonist
- Anti-remodeling action (bloc of aldosterone mediated cardiac hypertrophy/fibrosis)
- Raises serum K+ => no risk of hypokalemia
What are the adverse effects of K-sparing diuretics, specifically aldosterone antagonists? Especially consider effects to plasma electrolytes
- Hyperkalemia
- Endocrine abnormalities (gynecomastia w/ spironolactone) => blocks androgen receptor
- GI upset, drowsiness
Describe the renin-angiotensin-aldosterone system
- Renin converts angiotensinogen => angiotensin I
- ACE converts AI to angiotensin II
Ultimately increases BP via:
- vasoconstriction
- aldosterone secretion
- increased Na/H2O retention
- increased peripheral vascular resistance
Describe the contribution of chronic RAAS activation to the underlying pathology of HF
Chronic RAAS activation => exacerbates HF symptoms b/c of ^ BP and vasoconstriction
Also increases volume retention (this is what we target when using meds => OPTIMIZE FLUID RETENTION)
What is the target and MOA of ACEI?
- Targets ACE
- Inhibits ACE conversion of AI to AII
- Ultimately blocks AII-induced vasoconstriction => decreases preload and afterload
- Also prevents release of AII-induced aldosterone => decreases myocardial hypertrophy/remodeling
