Updated: 12/21/2019

Antianginal Drugs

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Snapshot
  • A 54-year-old man presents to the emergency department after experiencing pressure-like sternal chest pain that radiates down the left arm. Medical history is significant for hypertension, hypercholesterolemia, and type II diabetes. He smokes 2 packs of cigarettes per day for the past 25 years. On physical exam, the patient appears anxious and diaphoretic. An electrocardiogram demonstrates an ST-segment elevation in leads V1-V4. Cardiac troponins are sent. He is given aspirin, nitroglycerin, metoprolol, clopidogrel, and unfractionated heparin. The cardiac catheterization lab is activated .
Introduction
  • Appropriate treatment for acute coronary syndrome must be instituted immediately in order to
    • limit myocardial damage
    • decrease the risk of complications
    • restore the balance between myocardial oxygen supply and demand
NSTEMI and Unstable Angina (UA)
  • Introduction
    • NSTEMI and UA are managed in the same manner
    • the goal is to to provide 
      • anti-ischemic therapy
        • restores the myocardial oxygen supply and demand
      • anti-thrombotic therapy
        • prevents further growth of the partial thrombotic occlusion
  • Medications
    • anti-ischemic therapy
      • β-blockers (e.g., metoprolol)
        • mechanism
          • decreased sympathetic drive to the heart
            • promotes myocardial electrical stability
            • decreases myocardial demand
            • ↓ cAMP
          • improves mortality in patients with an MI
        • contraindications
          • bronchospasm
          • decompensated heart failure
          • hypotension
      • nitrates (e.g., nitroglycerin, isosorbide mononitrate, and dinitrate)
        • mechanism 
          • venodilation reduces preload to the heart, which reduces myocardial demand
            • recall that a reduction in preload reduces ventricular wall stress
          • afterload reduction and decreased SVR
          • coronary artery dilation improves blood flow to the myocardium
            • recall that venodilation >> arterial dilation
            • this can steal blood from already maximally dilated ischemic myocardium 
          • ↑ cGMP 
        • adverse events
          • nitroprusside causes cyanide toxicity
          • development of tolerance for the vasodilating action during the work week
          • a headache may result from vasodilation of cerebral arteries
          • can results in hypotension when combined with other blood pressure lowering medications
      • calcium channel blockers (e.g., verapamil and diltiazem)
        • mechanism
          • reduces heart rate and cardiac contractility
          • this medication is reserved for patients unresponsive to β-blockers and nitrates or have contraindications to β-blockers
            • this is because calcium channel blockers do not provide a mortality benefit
    • anti-thrombotic therapy
      • aspirin
        • mechanism
          • an inhibitor of thromboxane A2 synthesis 
            • thromboxane A2 is a prominent promoter of platelet activation
          • improves mortality and should be continued indefinitely
      •  P2Y12 ADP receptor inhibitor (e.g., clopidogrel and ticagrelor)
        • mechanism
          • prevents ADP from binding to the P2Y12 receptor, which would normally further activate platelets
    • anti-coagulation therapy
      • unfractionated heparin
        • mechanism
          • binds to antithrombin to enhance its effects
          • inhibits factor Xa
ST-Segment Elevation Myocardial Infarction (STEMI)
  • Introduction
    • STEMI suggest that there is a total occlusion of the vessel
      • thus the main goal is to induce rapid reperfusion via
        • percutaneous coronary intervention (PCI) OR
        • fibrinolytic therapy
      • patients are also given medications such as those used in NSTEMI and UA
        • aspirin
        • unfractionated heparin
        • β-blockers
        • nitrates
        • P2Y12 ADP receptor inhibitor 
  • Reperfusion therapy
    • primary PCI
      • the preferred method for reperfusion
      • must be performed within 90 minutes of first medical contact
        • aspirin and a P2Y12 receptor inhibitor is given prior to the procedure
    • fibrinolytic therapy (e.g., alteplase)
      • performed if PCI cannot be performed within 90 minutes or is unavailable
      • fibrinolytics convert plasminogen to plasmin, which degrades newly formed clots
Adjunctive Therapy
  • Angiotensin-converting enzyme (ACE) inhibitors (e.g., lisinopril)
    • provides a mortality benefit
    • prevents ventricular cardiac remodeling and reduces the rate of heart failure
  • Statins (e.g., atorvastatin) 
    • an HMG-CoA reductase inhibitor that lowers cholesterol levels
Therapy And Their Effect On Mortality
 
Effect on Mortality of Therapy Used in Acute Coronary Syndromes
Mortality Benefit
No Mortality Benefit
  • Aspirin
  • β-blockers
  • PCI
  • Statins
  • P2Y12 ADP receptor inhibitor 
  • Thrombolytics
  • Oxygen
  • Morphine
  • Nitrates
  • Calcium channel blockers
  • Lidocaine
  • Amiodarone
 

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