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Introduction
  • Symptoms of angina due to ischemia = myocardial oxygen demand exceeds supply
  • Goal is to ↓ myocardial O2 consumption (MVO2)
    • can achieve by reducing:
      • end diastolic volume (preload)
      • blood pressure
      • heart rate
      • contractility
      • ejection time
  • Can also ↑ O2 supply to myocardium
  • Main drugs include nitrates, beta-blockers, and calcium channel blockers
Nitrates
  • Examples
    • nitroglycerin, isosorbide dinitrate (also mononitrate), and nitroprusside 
  • Mechanism 
    • venodilation via generation of endothelial NO   
      • results in activation of guanylyl cyclase → ↑cGMP→ relaxation of smooth muscle   
      • dilate veins >> arteries 
    • ↓ EDV and ↓ BP → ↓ MVO2
    • reflex ↑ in contractility and HR
    • isosorbide mononitrate has highest oral bioavailability
  • Clinical use
    • angina  
    • pulmonary edema
    • aphrodisiac and erection enhancer
  • Toxicity
    • orthostatic hypotension
    • headache
      • due to vasodilation of cerebral arteries 
    • reflex tachycardia
    • tachyphylaxis
    • contraindicated in patients taking vasodilatory medication for erectile dysfunction (e.g. sildenafil)
      • severe hypotension
    • nitroprusside causes cyanide toxicity 
    • "Monday disease" seen in individuals with industrial exposure
      • development of tolerance for the vasodilating action during the work week 
      • loss of tolerance over the weekend
      • results in tachycardia, dizziness, headache on re-exposure
  • Arginine is a biochemical precursor of nitric oxide, and supplementation of this amino acid may have a role in augmenting the treatment regimen for chronic stable angina patients 
Beta-Blockers
  • Examples
    • propranolol, atenolol, and metoprolol
  • Mechanism
    • β-adrenergic antagonism 
      • results in ↓ cAMP
    • ↓ contractility, HR, and BP→ ↓ MVO2
  • Toxicity
    • impotence, depression, and bradycardia
    • pindolol and acebutolol are partial β-agonists
      • contraindicated in angina
Calcium Channel Blockers
  • Examples
    • nifedipine, verapamil, and diltiazem
  • Mechanism
    • ↓ vascular smooth muscle contractility  
      • result of inhibition of voltage-gated L-type Ca2+ channels
      • also affects cardiac tissue
      • nifedipine is most selective for vasculature
      • verapamil is most selective for heart
        • "Verapamil works on Ventricles"
    • ↓ afterload and ↓ AV node conduction velocity → ↓ MVO2
  • Clinical use
    • angina
    • hypertension
    • arrhythmias (not nifedipine) (see Antiarrhythmics)
    • vasospasm
      • Prinzmetal's angina
      • Raynaud's
  • Toxicity
    • cardiac depression
    • peripheral edema
    • AV block
    • headache
    • flushing
    • dizziness
    • constipation
 

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