Adenosine Receptor Based Antiarrhythmic Therapy

Adenosine is an endogenous nucleoside that acts on A1 receptors in the atrioventricular node to produce transient block, terminating re-entrant supraventricular tachycardia that depends on the node. Its effect lasts seconds, which makes it safe to give rapidly and useful for diagnosis. Adenosine triphosphate (ATP) acts through breakdown to adenosine and is used in some regions.

Mechanism. A1 receptor activation opens acetylcholine-sensitive potassium channels and inhibits calcium current, causing hyperpolarisation, slowed conduction and block in the atrioventricular node. A2A and A2B activation causes vasodilation. A3 activation contributes to bronchoconstriction in asthma.

Pharmacokinetics. Adenosine is taken up by red cells and endothelium and deaminated, giving a half-life under 10 seconds. It must be given as a rapid bolus into a large proximal vein followed by a saline flush.

Modulators. Methylxanthines (theophylline, aminophylline, caffeine) block adenosine receptors and reduce or abolish its effect. Dipyridamole blocks reuptake and increases its effect fourfold. Carbamazepine increases atrioventricular block.

Related agents. Regadenoson (A2A selective) and dipyridamole are used for pharmacological stress imaging.

• Adenosine: intravenous bolus for supraventricular tachycardia and diagnostic use.
• ATP: alternative in some regions; more bronchospasm and pain.
• Aminophylline and theophylline: antagonists.
• Dipyridamole: potentiator.
• Regadenoson and adenosine infusion: pharmacological stress testing.

• Regular narrow-complex tachycardia, after vagal manoeuvres fail: adenosine 6 mg rapid intravenous bolus, then 12 mg after 1 to 2 minutes if there is no response, and a further 12 mg if needed. Record a 12-lead electrocardiogram or rhythm strip during administration.
• Reduced dose: 3 mg when given through a central line, in heart transplant recipients, or in patients on dipyridamole or carbamazepine.
• Children: 100 micrograms/kg rapid bolus, then 200 micrograms/kg and 300 micrograms/kg (maximum single dose 12 mg).
• Diagnostic use: transient block of the node unmasks atrial flutter waves or atrial tachycardia, helping to diagnose a regular narrow-complex rhythm.
• Stress imaging: adenosine 140 micrograms/kg/minute for 4 to 6 minutes, with aminophylline available.
• Selection: first line for stable regular narrow-complex tachycardia. Not for irregular rhythm, and not a treatment for atrial fibrillation or flutter, though it may slow rate briefly.

Contraindications. Asthma or severe bronchospasm, second or third degree atrioventricular block or sick sinus syndrome without a pacemaker, long QT syndrome, and decompensated heart failure. Avoid in atrial fibrillation with pre-excitation, where blocking the node can speed conduction through the accessory pathway.

Adverse effects. Flushing, chest tightness, dyspnoea, a sense of impending doom, nausea, transient asystole or bradycardia for several seconds, ventricular ectopy, and atrial fibrillation after conversion. Patients should be warned beforehand. Bronchospasm can last longer in asthma.

Treatment of prolonged effects. Aminophylline 50 to 250 mg slowly intravenously for severe bronchospasm or prolonged block.

Interactions. Dipyridamole and carbamazepine increase effect. Theophylline and caffeine reduce effect. Verapamil or beta blockers given before can add block.

Monitoring. Continuous electrocardiography, blood pressure, and resuscitation equipment with defibrillator at hand.

Referral and escalation. Recurrent supraventricular tachycardia or a rhythm that fails to terminate needs cardiology review for ablation or maintenance therapy.

Special groups. Pregnancy: adenosine is safe for supraventricular tachycardia. Older adults: monitor for prolonged block. Heart transplant: use 3 mg because of supersensitivity. Caffeine intake: higher doses may be needed.