What is the mechanism of action of adenosine (adenosine)?

Mechanism of Action of Adenosine

Adenosine is a naturally occurring purine nucleotide that exerts its primary cardiac effects by selectively blocking AV nodal conduction through activation of specific purine receptors, particularly A1 receptors in cardiac tissue and A2 receptors in vascular tissue. 1, 2

Primary Mechanisms

• Adenosine acts through two main receptor subtypes: A1 and A2 receptors 1, 3

• A1 receptor activation (predominant cardiac electrophysiologic effect):

  • Causes direct negative chronotropic effect by suppressing cardiac pacemaker automaticity 2, 3
  • Produces negative dromotropic effect by inhibiting AV nodal conduction 2
  • Activates potassium outward current in atrial tissue, shortening action potential duration 4
  • Involves a pertussis toxin-sensitive N-protein in signal transduction from receptor to potassium channels 4

• A2 receptor activation (predominant vascular effect):

  • Causes coronary vasodilation through both endothelial-dependent and independent mechanisms 1, 3
  • Stimulates adenylate cyclase in vascular smooth muscle cells 1, 5

Cellular and Biochemical Effects

• Intracellular adenosine metabolism occurs via two pathways 1:

  • Phosphorylation to adenosine monophosphate by adenosine kinase
  • Deamination to inosine by adenosine deaminase

• Adenosine has an extremely short half-life (<10 seconds) in whole blood due to rapid cellular uptake 1

• Adenosine distribution occurs via a specific transmembrane nucleoside carrier system that is reversible and bidirectionally symmetrical 1

Clinical Applications in Arrhythmias

• Adenosine is the drug of choice for terminating AV nodal re-entrant tachyarrhythmias (PSVT) 2

• Adenosine can transiently slow ventricular rate in other SVTs (such as atrial fibrillation or flutter), which helps in diagnosis but does not typically terminate these arrhythmias 2

• In PSVT, adenosine is administered as a 6 mg rapid IV push through a large vein followed by a 20 mL saline flush; if no response within 1-2 minutes, a 12 mg dose can be given 2

Important Clinical Considerations

• Adenosine has important drug interactions that affect dosing 2:

  • Larger doses may be required with theophylline, caffeine, or theobromine due to competitive antagonism 2
  • Initial dose should be reduced to 3 mg in patients taking dipyridamole or carbamazepine, those with transplanted hearts, or when given by central venous access 2

• Common side effects are transient and include 2:

  • Flushing, dyspnea, and chest discomfort
  • Potential for transient complete heart block (must be given in monitored environment) 2

• Contraindications include 2:

  • Asthma (risk of bronchospasm)
  • Caution in patients with Wolff-Parkinson-White syndrome due to risk of initiating atrial fibrillation with rapid ventricular rates 2

Differential Effects in Cardiac Tissues

• In supraventricular tissues (atrial myocytes, sinoatrial node, and atrioventricular node), adenosine exerts both direct and indirect effects 3

• In ventricular tissue, adenosine primarily exerts indirect effects by antagonizing catecholamine-stimulated increases in contractility 3, 4

• Adenosine may have cardioprotective effects during ischemia by attenuating catecholamine release, inhibiting platelet and leukocyte activation, and preserving ATP 5, 6