Drugs acting on Renin-Angiotensin-Aldosterone System

Question 1

Components of RAAS

Answer 1

• Angiotensiongen converted to Angiotensin I
  
  • by Renin
• Angiotensin I converted to Angiotensin II
  
  • by ACE
• Angiotensin II acts on AT1 and AT2 receptors

Question 2

AT1 Receptor Effects

Answer 2

• Rapid Response: increases afterload
  
  • increase vasoconstriction
  • Increased NE release, decrease NE reuptake, inc response
  • Increase catecholamine release: CNS, adrenal medulla
• Slow response: increases volume (Preload)
  
  • Increase Na+ reabsorption
  • Increased aldosterone
  • Increased renal hemodynamics
    
    • constriction, catecholamine release, sympathetic tone
• Non-hemodynamic response:
  
  • increased proto-oncogenes
  • Increased growth factors
  • increases synth of ECM proteins

Question 3

Aliskiren

Answer 3

• Renin inhibitor
• Treat HTN
• Adverse: same as ARBs plus GI effects

Question 4

Captopril and Enalapril

Answer 4

• ACE inhibitors
• Prevent formation of angiotensin II
• Prevent degradation of bradykinin
• Use: HTN, CHF, HCM, MI, Renal failure/fibrosis, and Diabetes
• HTN: useful in pts w/ LV hypertrophy and ischemic heart disease
  
  • less effective in black patients
  • Better than diuretic/beta blockers in HTN diabetics for preventing CV events
• CHF: relax smooth muscle and allow increased EF, SV, and CO
  
  • Decreases congestion by decreasing afterload
  • Venodilation decrease preload and helps congestion
• slow diabetic neuropathy
• Contraindicated in Renal artery stenosis and elevated K+
• Adverse: hypotension, nonproductive cough, taste change, renal hemodynamic dysfunction, hyperkalemina, angioedema
• Interactions
  
  • NSAIDs: reduce antihypertensive effect, renal toxic
  • Digoxin: reduced dig clearance and false low
  • K+ sparing diuretics: hyperkalemia
  • Thiazide or loop diuretics: enhance hypotensive effects

Question 5

Losartan

Answer 5

• ARB: AT1 receptor blocker
• Interferes w/ angiotensin II binding to reeptor
• HTN:use w/ high or normal renin
  
  • mono if ACE intolerant, or in combo w/ others
  • Less effective in black pts
• CHF: reduces CV mortality and hospital admissions
• CAD: reduce CV events
• MI: reduce morbidity and mortality
• Stroke
• Contraindications and side effects similar to ACE

Question 6

Spironolactone and Eplerenone

Answer 6

• K sparing diuretics and aldosterone receptor antagonist
• Blocks action of aldosterone
• Aldosterone: secretion affected by angiotensin II, K+, ACTH
  
  • receptors in kidney, brain, heart, vessels
  • Actions: Na+ retention, K+ secretion, blood volume expansion, Increased BP
  • Antagonists block these action
• HTN: used alone or w/ others
• CHF: reduces morbidity, mortality, and hospitalizations
• Contraindicated: hyperkalemia, cirrhosis
• Adverse: hyperkalemia , gynacomastia, impotence, dysmenorrhea
• Interactions: digioxin (affects clearing)