Sites of Action for Cardiac Drugs

Snapshot

• A 24-year-old woman presents with tachycardia. She reports that this happens every few years without any identifiable causes. Her pulse is 200/min. Her other vital signs are stable. An electrocardiogram shows a patient with narrow complex QRS, tachycardia to 204/min, and a regular rhythm. She is given a medication to slow down the atrioventricular node and attempt to end the narrow complex tachycardia. (Adenosine)

Introduction

• Adenosine 
  • mechanism of action
    • ↑ K⁺ out of the cells, which hyperpolarizes the cell and causes ↓ AV nodal conduction
  • background
    • action potential is initiated by the sinoatrial (SA) node
      • slowed by the atrioventricular (AV) node
      • allows for ventricular filling prior to contraction
• Calcium channel blockers
  • mechanism of action
    • directly blocks L-type voltage-gated Ca²⁺ channels (dihydropyridine receptors) 
  • background
    • action potential causes a rush of Ca²⁺ into the cell
    • Ca²⁺ enters via L-type voltage-gated Ca²⁺ channels
    • this triggers the release of more Ca²⁺ from the sarcoplasmic reticulum
      • via ryanodine receptors
        • blocked by the ryanodine toxin
• Digoxin
  • mechanism of action
    • inhibits extracellular K⁺ binding site of the Na⁺-K⁺ATPase on myocyte cell membrane
      • when the ATPase is inhibited, ↑ Na⁺ intracellular concentration
      • Ca²⁺-Na⁺ exchanger decreases the amount of Ca²⁺ it pumps out of the cell
      • ↑ Ca²⁺ intracellular concentration
  • background
    • contractility is determined by intracellular Ca²⁺
      • positive inotropic agents increase intracellular Ca²⁺
• β-blockers
  • mechanism of action
    • indirectly blocks L-type voltage-gated Ca²⁺ channels (dihydropyridine receptors) via ↓ cAMP
  • background
    • positive inotropy by ↑ sympathetic nervous system is mediated by β1 receptors at the SA and AV nodes