Diuretics & RAAS Antagonists Flashcards Preview

CVPR: CV Unit I > Diuretics & RAAS Antagonists > Flashcards

Flashcards in Diuretics & RAAS Antagonists Deck (21):

Loop diuretics (Furosemide): Site/MOA @ nephron

  • Inhibit NaCl transport (Na+-K+2Cl- transporter) in the ascending limb of the loop of henle – more Na+, K+, and Cl- are retained in the urine

  • Associated with increased Mg2+ and Ca2+ excretion

  • Increase renal blood flow (via effect on renin-angiotensin system) 


Loop diuretics (Furosemide): Pharmacokinetics

  • Rapid oral absorption; extremely rapid IV response
  • Excreted by renal secretion and filtration
  • Furosemide duration of effect is 2-3 hours 


Loop diuretics (Furosemide): Role in HF therapy

  • Preferred class of diuretics in CHF due to greater efficacy
  • Used in HF patients with volume overload in conjunction with salt restriction
  • Furosemide is first line; if lack of response can increase dose or switch to bumetanide or torsemide
  • Patients with HF have reduced diuretic response due to decreased drug delivery to kidney due to decreased renal blood flow and hypoperfusion activation of RAAS
  • Refractory edema – may need to add a thiazide to block distal tubule Na+ reabsorption; may also add aldosterone antagonist
  • Acute pulmonary edema


Loop diuretics (Furosemide): Adverse effects

  • Hypokalemic metabolic alkalosis via enhanced secretion of K+ and H+
  • Hypokalemia predisposes to ectopic pacemakers and arrhythmias 
  • Ototoxicity
  • Hyperuricemia
  • Hypomagnesemia
  • Overdose --> rapid blood volume depletion 



Thiazides (Hyrdrochlorothiazide): Site/MOA @ nephron

  • Inhibit the Na+/Cl- cotransporter and increase urinary excretion of NaCl (a modest diuretic effect since only 5-10% of filtered Na+ is reabsorbed here)
  • Increase reabsorption of Ca2+ (lowering of intracellular Na+ drives Ca2++ exchanger) 


Thiazides (Hyrdrochlorothiazide): Pharmacokinetics

  • Oral absorption, best tolerated early in the day
  • Hydrochlorothyozide – twice daily dosing
  • Secreted by organic acid secretory system; competition with uric acid secretion may precipitate gout attacks 


Thiazides (Hyrdrochlorothiazide): Role in HF therapy

  • First line for mild hypertension
  • Tx for Hypercalcuria – increased reabsorption of Ca2+ --> reduced urinary excretion --> decreases incidence of kidney stones
  • CHF/refractory edema: synergistic diuretic effect with loop diuretics


Thiazides (Hyrdrochlorothiazide): Adverse effects

  • Hypokalemia --> predisposition to ectopic pacemakers; contraindicated in patients with arrhythmias, MI, angina
  • Hyperuricemia – avoid in patients with gout
  • Impaired carbohydrate tolerance (hyperglycemia, glucosuria) and hyperlipidemia 


Potassium-sparing diuretics: Site/MOA @ nephron

  • In the collecting tubule, the driving force for Na+ into the cell exceeds that for K+ exit so Na+ enters the cell from the lumen and the lumen becomes negative, driving Cl- into cells and K+ into the urine;
  • thus, K+ excretion is coupled to Na+ reabsorption and ALL diuretics that cause a greater delivery of Na+ to this site via greater tubular flow will enhance K+ excretion
  • Aldosterone, through effects on gene transcription, increases both the number and activity of Na+ and K+ membrane channels, as well as the Na/K ATPase
  • Diuretics that block the Na+ channel or antagonize the aldosterone receptor will decrease Na+ reabsorption and decrease K+ excretion 


Aldosterone Antagonists (Sprionolactone): Site/MOA

  • competitive antagonist at aldosterone receptor
  • prevents enhancement of protein synthesis; blockade of aldosterone effect at collecting tubule
  • --> less Na+ is reabsorbed, lumen potential becomes more positive, and less K+ ions move into the urine
  • Promotes only moderate increase in Na+ excretion; mild diuresis when used alone 



Aldosterone Antagonists (Sprionolactone): Pharmacokinetics

  • Poor oral absorption

  • dosed 1-2x/day with slow onset of action 


Aldosterone Antagonists (Sprionolactone): Clinical uses

  • Congestive heart failure
    • Block aldosterone receptors on the heart – anti-remodeling action, blocking deleterious effects of aldosterone on the heart (hypertrophy, fibrosis)
  • Raises serum potassium to counter risk of hypokalemia-induced arrhythmias resulting from K+ wasting diuretics
  • Hyperaldosteronism
  • HTN 



Aldosterone Antagonists (Sprionolactone): Adverse Rxns

  • Hyperkalemia --> arrhythmias
  • Endocrine abnormalities (gynecomastia with spironolactone via secondary blockage of androgen receptor ~10%) 


ACE inhibitors (Lisinopril): Site/MOA

  • Inhibits ACE conversion of AI to AII, blocking AII induced vasoconstriction; results in decreased pre-load and afterload

  • Decreases AII-induced release of aldosterone, which moderates the myocardial hypertrophy and remodeling response

  • Decreases bradykinin inactivation, increasing vasodilation

  • Improves endothelial function via enhancement of NO action

  • Reduces sympathetic activity 


ACE inhibitors (Lisinopril): Pharmacokinetics

  • Well absorbed orally

  • All except Lisinopril and captopril are pro-drugs that are metabolized to the active drug in the liver

  • Active metabolites are eliminated by the kidney, requiring dosage adjustment in patients with renal insufficiency

  • Once daily dosing for most agents 


ACE inhibitors (Lisinopril): Role in HF therapy

  • first line tx of hypertension


ACE inhibitors (Lisinopril): Adverse effects

  • cough
  • hyperkalemia
  • hypotension (if hypovolemic)
  • acute renal failure


Angiotensin Receptor Blockers (Losartan): Site/MOA

  • Selective inhibition of AII receptor

  • Similar mechanism of action as ACEIs 


Angiotensin Receptor Blockers (Losartan): Role in HF therapy

  • Potential for more complete inhibition of AII action since alternative pathways exist to form AII that are NOT blocked by ACEIs
  • No side effects mediated by increased bradykinin levels (cough); however, loss of increased vasodilation 


Angiotensin Receptor Blockers (Losartan): Pharmacokinetics

  • Oral dosing, once daily except for losartan (twice daily)
  • Decreased losartan dose necessary in hepatic dysfunction 


Angiotensin Receptor Blockers (Losartan): Adverse effects

  • Similar to ACEIs but no cough
  • Contraindicated in pregnancy