Adenosine

Article Author:
Shashank Singh
Article Editor:
Rebecca McKintosh
Updated:
7/29/2018 12:13:37 PM
PubMed Link:
Adenosine

Indications

Adenosine is used as a diagnostic or therapeutic agent. Diagnostically, adenosine is used in a myocardial perfusion stress imaging study for its vasodilatory effects. Therapeutically, adenosine is used for its antiarrhythmic properties in supraventricular tachycardia (SVT) and can function as a diagnostic tool as well depending on the type of SVT.

Mechanism of Action

Adenosine is a purine nucleoside base, most commonly recognized with the molecule adenosine triphosphate, or ATP, and is used thoroughly throughout the entire body in general metabolism. Adenosine’s use as a pharmacological drug works through receptors called purinergic adenosine receptors found throughout the body. Samsel et al. describe four types of adenosine receptors: A1, A2a, A2B, and A3 effecting the immune, nervous, circulatory, respiratory and urinary system. Most notably, receptors found in the cardiac atrioventricular (AV) nodal tissue and within the peripheral vasculature are what exhibit clinical manifestations when adenosine is administered.

Adenosine can be further classified as a miscellaneous antiarrhythmic drug outside the Vaughan-Williams classification scheme. It acts on receptors in the cardiac AV node, significantly reducing conduction time. This occurs by activation of specific potassium channels, driving potassium outside of cells, and inhibition of calcium influx, disrupting the resting potential of the slow nodal cardiac myocyte. Driving potassium outside of the cell causes hyperpolarization of the resting membrane potential while slowing of calcium influx causes suppression of calcium-dependent action potentials, all requiring a longer time for depolarization to occur and thus slowing down conduction within these cells, which is useful in SVT.  SVT is defined as any arrhythmia originating above and including the bundle of His and specifically excludes atrial fibrillation by the ACC/AHA 2015 guidelines. Usually narrow complex, SVT consists of several specific arrhythmias, which at a high rate (greater than 150 beats per minute), is difficult to diagnosis.  Adenosine has a role in slowing down the heart rate enough to assist in diagnosis. It can also terminate specific reentrant tachycardia involving the AV node including AV nodal reentrant tachycardia (AVNRT), orthodromic AV reentrant tachycardia (AVRT), and antidromic AVRT although extreme caution should be used when administered for antidromic AVRT as adenosine should be used only if the diagnosis is known.

The objective of a cardiac stress test is to evaluate the patient for significant, stable coronary artery disease and/or prognosis through the induction of ischemia. Adenosine’s role in the cardiac stress test is as a pharmacologic component of stressing the heart through vasodilation, causing ischemia through a mechanism called a coronary steal.  Adenosine, with the use of a radiotracer for imaging, composes a nuclear cardiac stress test. Use of adenosine in cardiac testing is favorable to evaluate patients who have a baseline left bundle branch block morphology on the electrocardiogram. Its limitations, however, are that it can not evaluate prognosis through functional status as there is no exercise component to the cardiac stress test with adenosine.

Drug Metabolism

Adenosine has a rapid onset of action with a very short half-life and undergoes rapid intracellular metabolism, either by phosphorylation, forming adenosine monophosphate, or deamination. Phosphorylation, via adenosine kinase, allows adenosine to be further metabolized as cellular energy while deamination occurs by adenosine deaminase, eventually forming xanthine and further metabolized into uric acid.

Administration

Adenosine is administered intravenously in specific clinical cases. For management of SVT, adenosine is ideally given through a peripheral intravenous (IV) access initially as a 6-mg dose followed by a 20-mL saline flush for rapid infusion. Subsequent doses are given starting at 12-mg doses and also followed by 20-mL saline for rapid infusion. The initial dose of adenosine is reduced to a 3-mg bolus if it is given through an intravenous line that accessed into the central circulation, those on dipyridamole or carbamazepine, or if the patient is a cardiac transplant recipient.

Administration for pharmacological cardiac stress testing is intravenously as well, however in a continuous fashion rather than bolus therapy as with SVT. The dose of adenosine used in cardiac stress testing is weight based and usually administered as 140 mcg/kg per minute.

Adverse Effects

Adenosine’s adverse effects are secondary to the activation of adenosine receptors found on vascular tissue causing vasodilation. Symptoms of skin flushing, lightheadedness, nausea, sweating, nervousness, numbness, feeling of impending doom have all been described; however, these effects are very transient and short-lived secondary to adenosine’s short half-life.

More severe symptoms are cardiac related and include the development of cardiac arrhythmia including premature atrial contractions and premature ventricular contractions, development of AV block, cardiac ischemia, hypotension and prolonged asystole. These effects should be communicated to the patient before any administration.

Although presenting a lesser adverse effect, it is important to review certain drug-drug interactions involving adenosine. The effects of adenosine can be blocked by caffeine and theophylline, which fall under a class of drugs called methylxanthines. Methylxanthines are derived from another purine base, xanthine, which has a chemical structure similar enough to that of adenine, that they can bind to adenosine receptors acting as a competitive antagonist to adenosine. Patients on these drugs may require larger doses.

Other drug-drug interactions to consider when administering adenosine is the simultaneous use with carbamazepine and dipyridamole. Both these drugs may enhance the adverse effects of adenosine, and a decreased initial dose should be used.

Contraindications

Absolute contraindications include known hypersensitivity to adenosine, heart block or clinical active bronchospasm, either secondary to reactive airway disease, chronic obstructive pulmonary disease (COPD), or asthma.

Extreme caution should be emphasized with adenosine administration in any patient with SVT involving an accessory pathway, including Wolf-Parkinson-White (WPW) syndrome. In general, adenosine should not be used in irregular or polymorphic wide-complex tachycardias, a class III recommendation as the administration can cause degeneration into ventricular fibrillation. Even in the setting of known antidromic AVRT, because of underlying atrial fibrillation, blocking the AV nodal tissue can cause unhindered conduction from the atria to the ventricle through this accessory pathway. While adenosine can slow conduction through the AV node, it does not affect accessory pathways. In such cases, this can cause severe tachycardia that can deteriorate to a non-perfusing rhythm, leading to cardiac arrest.

Of note, pregnancy is not a deterrent for adenosine administration.

Monitoring

Any patient receiving adenosine should be on a form of cardiac monitoring. Patients being treated for SVT are often on a 12-lead electrocardiogram rhythm monitoring to assess the underlying rhythm while adenosine is actively affecting the AV node. In any case, where WPW is considered, a defibrillator should be available in case of rapid decompensation.

Toxicity

Due to the rapidly short half-life of adenosine, toxic effects of adenosine are kept to a minimum, although severe effects of prolonged asystole, development of heart block, and cardiac ischemia have been noted with adenosine. There is no a reversible agent, however, unless a permanent injury is sustained, these effects are transient, and patients should be supported appropriately.