52. Hypertension & Cardiac Failure

Question 1

Name the diuretics that can be used to treat high blood pressure

Answer 1

• Loop diuretics
  
  • e.g. furosemide
• Thiazides
  
  • ​e.g. bendroflumethiazide
• ​Potassium-sparing diuretics
  
  • ​e.g. spironolactone & amiloride

Question 2

What class is furosemide? What is its mechanism of action?

Answer 2

• Loop diuretic
  
  • ​Rapid onset
  • Short half life
  • Very powerful
• Inhibit Na/K/Cl co-transporter in the thick ascending limb
  
  • ​Blocking sodium absorption
• Inhibit Na/K/Cl co-transporter at the macula densa
  
  • ​Reducing sodum and chlorine transproted into the macula densa cells
  • Stimulates the release of renin (compensatory mechanisms)
    
    • Angiotensinogen –> angiotensin I
      
      • ​Angiotensin II stimulates:
        
        • ​ADH
          
          • Activation of AQ2
            
            • ​AQ1 is stable
        • Aldosterone
          
          • ​Activates basolaterla Na+/K+ pumps

Question 3

What class is bendolfumethiazide? What is its mechanism of action?

Answer 3

• Thiazides
  
  • Mild diuretic effect
  • Commonly prescribed
• Mechanism
  
  • ​Inhibiting Na⁺/Cl^- co-transproter in the distal tubule
    
    • ​Reducing active transport of Na⁺ and Cl^-
      
      • ​Mild effect due to relatively little sodium at distal tubules
      • ​​Less likely to result in hypokalaemia

Question 4

What class is spironolactone? What is it mechanism of action?

Answer 4

• Potassium-sparing diuretics
• ​​Mechanism
  
  • ​Act on distal tubule
  • ​​Direct aldosterone antaognist

Question 5

What class is amiloride? What is its mechanism of action?

Answer 5

• Potassium-sparing diuretics
• Mechanism
  
  • Directly blocking sodium epithelial channel (ENac) in late distal tubules
• Not to be confused with amiodarone = K⁺ channel blocker

Question 6

What class is ramipril? What is its mechanism of action?

Answer 6

• ACE inhibitors
• Mechanism
  
  • ​Inhibit the actions of angiotensin converting enzyme (ACE)
    
    • ​Preventing conversion of angiotensin I into angiontensin II
  • ​Acts as Na⁺/H⁺ exchanger in proximal tubules to stimulate Na⁺ reabsorption and H⁺ excretion

Question 7

What class is doxazosin? What is its mechanism of action?

Answer 7

• Beta blocker
• Mechanism
  
  • Competitive inhibitor of G_q alpha-1 adrenergic receptor
    
    • ​Alpha 1 = usually found in smooth muscle and sphincters
  • Prevents the cleavage of PIP₂ into IP₃ and DAG
    
    • ​IP₃ binds to ligand-gated calcium channels
    • DAG activates PKA which normally phospharylates and actives MLCK

Question 8

What class is prazosin? What is its mechanism of action?

Answer 8

• Inverse agonist at the alpha-1 receptor
• Prevents the cleavage of PIP₂ into IP₃ and DAG
  
  • ​IP₃ binds to ligand-gated calcium channels
  • DAG activates PKA which normally phospharylates and actives MLCK

Question 9

What class is glyceryl trinitrate? What is its mechanism of action?

Answer 9

• Nitrovasodilator
• Mechanism
  
  • ​Prodrug that must be dinitrated to produce the active metabolite nitrous oxide (NO)
  • Activates guanylate cyclase which converts guanosine triphosphate (GTP) into cyclic guanosine monophosphate (cGMP)
  • cGMP then activates protein kinase G (PKG) which then inhibits myosin light chain kinase (MLCK)

Question 10

What class is nifedipine? What is its mechanism of action?

Answer 10

• Calcium channel blocker
• Blocks L-type Ca²⁺ voltage-gated calcium channel in vascular muscle
  
  • ​Prevnets rise in [Ca²⁺_]i

Question 11

What class is verapamil? What is its mechanism of action?

Answer 11

• Calcium channel blocker
• Blocks L-type Ca²⁺ voltage-gated calcium channel in vascular muscle
  
  • ​Prevnets rise in [Ca²⁺_]i

Question 12

What class is propanolol? What is its mechanism of action?

Answer 12

• Cardiovascular target
  
  • Beta blocker
• Mechanism
  
  • Non-selective competitive antagonist of beta adrenergic receptor
    
    • ​Atenolol = beta 1 selective
  • Inhibits activity of adenylate cyclase, inhibits cAMP, leading to reduced PKA production
  • Reduced calcium influx into cardiac mycocytes through voltage-gated L channels
    
    • Reduced heart rate, decreased cardiac output