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Cardiovascular Drug Introduction
  • Cardiovascular medications can be broken down into the following categories
    • Antiarrhythmics
    • Antihypertensives
    • Inotropes
    • Vasodilators
    • Diuretics
    • Antihyperlipidemics
    • Anti-plateletes
    • Thrombolytics
Introduction
  • Symptoms of angina due to myocardium oxygen demand exceeding supply
  • Goal is to ↓ myocardial O2 consumption (MVO2)
    • can achieve by reducing
      • end diastolic volume
      • 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), nitroprusside
  • Mechanism 
    • venodilation via generation of endothelial NO
      • results in activation of guanyl cyclase → ↑cGMP → relaxation of smooth muscle 
      • dilate veins >> arteries 
    • ↓ EDV, ↓ BP → ↓ MVO2
    • reflex ↑ in HR
    • isosorbide mononitrate has highest oral bioavailability
  • Clinical use
    • angina
    • pulmonary edema
    • aphrodesiac and erection enhancer
  • Toxicity
    • orthostatic hypotension
      • especially in combination with other antihypertensives
    • 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" in 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
Beta-Blockers
  • Examples
    • propanolol, atenolol, metoprolol
  • Mechanism
    • beta-adrenergic antagonism
      • results in ↓ cAMP
    • ↓ contractility, HR, BP→ ↓ MVO2
  • Toxicity
    • impotence, depression, bradycardia
    • pindolol and acebutolol are partial β-agonists
      • contraindicated in angina
Calcium Channel Blockers
  • Examples
    • nifedipine, verapamil, 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, ↓ 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
    • flushing
    • dizziness
    • constipation
 

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