Adenosine

Mechanism of action

Adenosine is an endogenous nucleoside that binds to A1 adenosine receptors on cardiac tissue, particularly at the atrioventricular (AV) node. A1 receptor activation triggers several electrophysiologic effects:

• Increases potassium conductance via activation of acetylcholine-sensitive potassium channels (IKAdo), leading to hyperpolarization of nodal cells
• Decreases calcium influx through L-type calcium channels, reducing action potential upstroke velocity
• Inhibits adenylyl cyclase, reducing cAMP formation and decreasing sympathetic effects

These actions result in slowed AV nodal conduction and prolonged AV nodal refractoriness, which interrupts re-entrant circuits involving the AV node. The drug transiently blocks AV conduction, causing a brief pause in ventricular depolarization that terminates most forms of PSVT. The sinoatrial (SA) node is also affected, but to a lesser extent.

Adenosine does not affect accessory bypass tracts (e.g., in Wolff-Parkinson-White syndrome) or ventricular tissue significantly. Its effects are extremely short-lived due to rapid cellular uptake and metabolism by adenosine deaminase and adenosine kinase in red blood cells and vascular endothelium.

Indications

Acute termination of PSVT

Adenosine is first-line therapy for acute termination of paroxysmal supraventricular tachycardia, particularly:

• AV nodal re-entrant tachycardia (AVNRT) — most common form of PSVT
• AV re-entrant tachycardia (AVRT) involving the AV node as part of the re-entry circuit
• Termination rate approaches 90-95% for AVNRT when administered properly

Adenosine is not effective for atrial fibrillation, atrial flutter, or ventricular tachycardia, but may transiently slow the ventricular response and unmask the underlying atrial rhythm, aiding diagnosis.

Pharmacologic stress testing

Adenosine is used as a coronary vasodilator during myocardial perfusion imaging in patients who cannot exercise adequately. It causes coronary vasodilation via A2A receptors on vascular smooth muscle, creating a flow differential between normal and stenotic coronary arteries (coronary steal phenomenon).

Diagnostic use

The transient AV block produced by adenosine can help differentiate wide-complex tachycardias and unmask underlying atrial activity in uncertain rhythms.

Pharmacokinetics

Adenosine has unique pharmacokinetic properties driven by its status as an endogenous molecule:

Absorption and distribution: Administered only as rapid intravenous bolus. Oral bioavailability is negligible due to extensive first-pass metabolism. Must be given as close to the heart as possible (preferably via antecubital or more central line) followed immediately by a saline flush to ensure drug reaches the heart before degradation.

Metabolism: Extremely rapid uptake by erythrocytes and vascular endothelial cells. Metabolized by adenosine deaminase (to inosine) and adenosine kinase (to AMP). The half-life is less than 10 seconds, with effects terminating within 1-2 minutes.

Elimination: Metabolites are further degraded to uric acid and ultimately excreted renally. No dosage adjustment is needed in renal or hepatic impairment due to the rapid extrahepatic and extrarenal metabolism.

Special considerations: The extremely short half-life means that timing of administration is critical. Delayed flush or slow push results in drug metabolism before reaching cardiac tissue. Higher doses may be needed when administered via peripheral rather than central access.

Adverse effects

Most adverse effects are transient, lasting less than one minute, due to the ultra-short half-life:

Cardiovascular

• Transient asystole or AV block — expected effect, typically 3-15 seconds; may be frightening to patient and staff but resolves spontaneously
• Flushing (very common, up to 40% of patients) due to peripheral vasodilation
• Chest discomfort or pressure (common) — may mimic angina but is not ischemic; due to adenosine receptor activation in the chest wall and airways
• Hypotension (transient)
• Rarely, adenosine may precipitate atrial fibrillation (1-2% of cases)

Respiratory

• Dyspnea (common, up to 35%) — sensation of "can't catch my breath"
• Bronchospasm — particularly dangerous in patients with asthma or COPD; mediated by A1 and A2B receptors in airways

Neurologic

• Headache
• Lightheadedness or dizziness

Other

• Nausea
• Metallic taste

Patients should be warned that they will experience very unpleasant but brief sensations. Continuous ECG monitoring and resuscitation equipment must be immediately available. Most adverse effects require no treatment due to rapid spontaneous resolution.

Contraindications and warnings

Absolute contraindications

• Second- or third-degree AV block or sick sinus syndrome (unless patient has functioning pacemaker) — risk of prolonged asystole
• Severe asthma or bronchospastic lung disease — adenosine can precipitate life-threatening bronchospasm
• Known hypersensitivity to adenosine

Relative contraindications and warnings

• Atrial fibrillation/flutter with pre-excitation (Wolff-Parkinson-White syndrome) — adenosine may increase conduction down the accessory pathway, potentially causing ventricular fibrillation. However, if the re-entrant circuit involves the AV node (orthodromic AVRT), adenosine is appropriate.
• Recent myocardial infarction or unstable angina — use with caution
• Autonomic dysfunction — exaggerated hypotensive response possible
• Cerebrovascular disease — transient ischemia possible due to vasodilation and steal
• Heart transplant patients — hypersensitive to adenosine effects; require significantly reduced doses (starting at 0.5-1 mg) due to denervation hypersensitivity

Drug interactions affecting response

• Methylxanthines (theophylline, caffeine) are competitive adenosine receptor antagonists and may prevent adenosine's effects; higher doses may be required
• Dipyridamole blocks adenosine reuptake and inhibits phosphodiesterase, potentiating and prolonging effects; smaller doses are required
• Carbamazepine may potentiate AV block

Pregnancy and lactation

Pregnancy category C. Limited human data, but no evidence of teratogenicity. Use when benefit outweighs risk; generally considered acceptable for acute PSVT termination in pregnancy when necessary.

Drug interactions

Adenosine's ultra-short half-life limits most drug interactions, but certain medications significantly alter its effects:

Agents that antagonize adenosine

• Theophylline and aminophylline — competitive antagonists at adenosine receptors; can completely block adenosine's effects. Larger doses of adenosine (up to 12 mg or higher) may be required, or alternative agents should be considered.
• Caffeine — also a methylxanthine that antagonizes A1/A2 receptors. Patients should avoid caffeine for 12-24 hours before adenosine stress testing. Clinical doses of adenosine for PSVT usually overcome caffeine blockade.

Agents that potentiate adenosine

• Dipyridamole — inhibits cellular adenosine uptake (via ENT1 transporter) and phosphodiesterase, markedly increasing adenosine levels and effects. Reduce adenosine dose to 0.25-0.5 mg if coadministration is necessary. Warn patients that dipyridamole is often combined with aspirin (Aggrenox).
• Carbamazepine — may increase degree of heart block; use with caution

Other interactions

• Digoxin and verapamil — theoretical additive effects on AV nodal conduction, but clinically adenosine is used safely in patients on these medications
• No significant interactions with beta-blockers, though both slow AV conduction

Clinical pearl: Always ask about caffeine intake and medications before adenosine stress testing. For acute PSVT termination, the brief duration of action makes most interactions clinically manageable.

Clinical pearls

Administration technique is critical

• Use rapid IV push (1-2 seconds) followed immediately by 20 mL saline flush, then elevate the arm. The drug must reach the heart before being metabolized.
• Administer via the most proximal IV access possible (antecubital or higher). Smaller, more distal IVs require higher doses.
• Initial dose: 6 mg; if no response after 1-2 minutes, give 12 mg; may repeat 12 mg once more if needed.

Patient counseling is essential

• Warn patients before administration: "You will feel very uncomfortable for about 30 seconds — chest pressure, difficulty breathing, flushing — but it will pass quickly."
• The sensation of impending doom is common but transient. Reassurance during and after administration improves patient tolerance.

ECG monitoring pearls

• Continuous ECG recording during administration documents the rhythm strip and termination of PSVT, which is valuable for diagnosis and documentation.
• Transient asystole of 5-15 seconds is expected and normal — resist the urge to intervene unless it persists beyond 15-20 seconds.
• If PSVT does not terminate, adenosine helps diagnostically by briefly revealing underlying atrial activity.

When adenosine fails

• Failure to terminate PSVT may indicate incorrect diagnosis (e.g., atrial flutter, atrial fibrillation, VT) or inadequate drug delivery.
• Consider inadequate administration technique (slow push, distal IV, inadequate flush) before concluding treatment failure.
• Caffeine or theophylline use may require higher doses.

Special populations

• Heart transplant recipients: Start with 1 mg or less due to denervation hypersensitivity.
• Central line administration: Consider reducing dose by 25-50% as drug delivery to the heart is more direct.
• Pregnancy: Preferred over many other antiarrhythmics for acute PSVT due to lack of fetal effects.

Practice questions

Frequently asked questions

Conditions it is used for

Related drugs

Sources and further reading

DailyMed (FDA labels)StatPearls (NCBI Bookshelf)MedlinePlusWHO ATC/DDD index: C01EB10

Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.