What are the cardiac effects of adenosine?

Cardiac Effects of Adenosine

Adenosine primarily acts on cardiac tissue by activating purine receptors, causing negative chronotropic, dromotropic, and inotropic effects on the heart through A1 receptor activation, while producing peripheral vasodilation through A2 receptor activation. 1, 2

Mechanism of Action

• Adenosine exerts its cardiac effects through activation of specific cell surface purine receptors, particularly A1 receptors in cardiac tissue and A2 receptors in vascular tissue 1, 2
• A1 receptor activation causes direct negative chronotropic effects by suppressing cardiac pacemaker automaticity 1, 2
• A1 receptor activation produces negative dromotropic effects by inhibiting AV nodal conduction 1, 2
• A1 receptor activation causes negative inotropic effects, decreasing cardiac contractility 2
• A2 receptor activation produces peripheral vasodilation 2
• These effects are not influenced by muscarinic blockade with atropine, indicating a direct mechanism of action rather than vagally mediated effects 3

Electrophysiologic Effects

• Adenosine selectively blocks AV nodal conduction, making it effective for terminating AV nodal re-entrant tachyarrhythmias 1, 4
• It suppresses sinus node automaticity, causing transient sinus bradycardia 3
• It has minimal to no effect on antegrade conduction over accessory pathways in Wolff-Parkinson-White syndrome 3
• It can cause transient AV block during atrial flutter or atrial fibrillation but does not terminate these arrhythmias 3
• It can transiently slow ventricular rate in atrial fibrillation or flutter, which helps in diagnosis but does not typically terminate these arrhythmias 5

Hemodynamic Effects

• The net effect of adenosine in humans is typically a mild to moderate reduction in systolic, diastolic, and mean arterial blood pressure 2
• This is often associated with a reflex increase in heart rate 2
• Rarely, significant hypotension and tachycardia have been observed 2
• Adenosine causes cardiac vasodilation which increases coronary blood flow, particularly in normal coronary arteries with little or no increase in stenotic arteries 2

Pharmacokinetics

• Adenosine has an extremely short half-life of less than 10 seconds in whole blood 4, 2
• It is rapidly distributed from circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells 2
• Intracellular adenosine is metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase or via deamination to inosine by adenosine deaminase 2
• This rapid metabolism accounts for its very brief duration of action 2, 6

Clinical Applications

• Adenosine is the drug of choice for terminating AV nodal re-entrant tachyarrhythmias (PSVT) 5
• It 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 5, 4
• It has a success rate of approximately 90-95% in terminating PSVT 7, 6
• It can be used diagnostically in wide-complex tachycardias to differentiate supraventricular from ventricular origins 5
• It should be used with caution when the diagnosis is unclear as it may produce ventricular fibrillation in patients with coronary artery disease 5

Adverse Effects and Precautions

• Common side effects include flushing, chest discomfort/pain, dyspnea, and transient AV block, which are usually transient and last less than 60 seconds 5, 4
• Adenosine should be avoided in patients with severe bronchial asthma due to risk of bronchospasm 5
• It should be used with caution in patients with pre-excited atrial fibrillation due to the risk of accelerated ventricular response 5, 4
• Important drug interactions include:
  • Enhanced effect with dipyridamole 5, 4
  • Reduced effect with theophylline, caffeine, or theobromine 5, 4
  • Higher rates of heart block when used with carbamazepine 5, 4
• 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 5, 4
• Adenosine must be given in a monitored environment as it can cause transient complete heart block 5

Comparison with Other Agents

• Compared to verapamil, adenosine has a more rapid onset of action and fewer severe side effects for terminating PSVT 5, 7
• Unlike calcium channel blockers or beta-blockers, adenosine does not cause prolonged depression of myocardial contractility 5, 6
• Its extremely short half-life makes it safer than other antiarrhythmic agents, particularly in patients with heart failure or hypotension 6