Adenosine

Article Author:
Shashank Singh
Article Editor:
Rebecca McKintosh
Updated:
10/16/2019 11:38:01 AM
PubMed Link:
Adenosine

Indications

Adenosine can serve as a diagnostic or therapeutic agent. Diagnostically, adenosine is one pharmaceutical agent 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.[1] 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, affecting 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 administering adenosine.[2][3]

Adenosine further classifies as a miscellaneous antiarrhythmic drug outside the Vaughan-Williams classification scheme. It acts on receptors in the cardiac AV node, significantly reducing conduction time.[3] This effect 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.[4] Usually narrow complex, SVT consists of several specific arrhythmias, which at a high rate (greater than 150 beats per minute), is difficult to diagnose.  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 is necessary when administering adenosine for antidromic AVRT as it should be used only if the diagnosis is certain.

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 a pharmacologic component of stressing the heart through vasodilation, causing ischemia through a mechanism called a coronary steal.[5] Adenosine, with the use of a radiotracer for imaging, composes a nuclear cardiac stress test. The 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 assess 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 the 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 start at 12 mg, also followed by 20-mL saline for rapid infusion.[6] The initial dose of adenosine is reduced to a 3 mg bolus if 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.[6]

Adverse Effects

The adverse effects of adenosine 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.[6]

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. The clinician should communicate information to the patient regarding these possible effects before any administration.

Although presenting a lesser adverse effect, it is essential to review specific 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 derive 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.[7]

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; the clinician should use a decreased initial dose. 

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.[8]

Extreme caution requires emphasis with adenosine administration in any patient with SVT involving an accessory pathway, including Wolf-Parkinson-White (WPW) syndrome. In general, the clinician should not use adenosine 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.[9]

Toxicity

Due to the rapidly short half-life of adenosine, toxic effects of adenosine are kept to a minimum, although there have been reports of severe effects involving prolonged asystole, development of heart block, and cardiac ischemia with adenosine. There is not a reversal agent; however, unless the patient sustains a permanent injury, these effects are transient, and patients should receive appropriate supportive measures.

Enhancing Healthcare Team Outcomes

Healthcare workers, including nurse practitioners who plan to use adenosine, should be very familiar with the indications and contraindications. Any patient receiving adenosine should be on a form of cardiac monitoring. Patients receiving treatment 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 cases of WPWd, a defibrillator should be available in case of rapid decompensation. If one has never used adenosine before, it is important to first speak to a cardiologist.

It would also benefit the clinician to consult a cardiology board-certified pharmacist to ensure proper dosing for the application at hand. Cardiology specialty-trained nursing staff can also assist in administering the drug, helping during a pharmacological stress test, or followup when using adenosine therapeutically. Open communication must exist between the clinician, cardiologist, nursing, and pharmacists so that an interprofessional team works the case, and the patient receives optimal benefit. [Level V]


References

[1] Samsel M,Dzierzbicka K,Trzonkowski P, [Adenosine, its analogues and conjugates]. Postepy higieny i medycyny doswiadczalnej (Online). 2013 Dec 3;     [PubMed PMID: 24379260]
[2] Mosqueda-Garcia R, Adenosine as a therapeutic agent. Clinical and investigative medicine. Medecine clinique et experimentale. 1992 Oct     [PubMed PMID: 1458718]
[3] Rankin AC,Brooks R,Ruskin JN,McGovern BA, Adenosine and the treatment of supraventricular tachycardia. The American journal of medicine. 1992 Jun     [PubMed PMID: 1605147]
[4] Page RL,Joglar JA,Caldwell MA,Calkins H,Conti JB,Deal BJ,Estes NAM 3rd,Field ME,Goldberger ZD,Hammill SC,Indik JH,Lindsay BD,Olshansky B,Russo AM,Shen WK,Tracy CM,Al-Khatib SM, 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology. 2016 Apr 5     [PubMed PMID: 26409259]
[5] Henzlova MJ,Duvall WL,Einstein AJ,Travin MI,Verberne HJ, ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2016 Jun     [PubMed PMID: 26914678]
[6] Verani MS, Pharmacological stress with adenosine for myocardial perfusion imaging. Seminars in nuclear medicine. 1991 Jul     [PubMed PMID: 1948115]
[7] Riksen NP,Smits P,Rongen GA, The cardiovascular effects of methylxanthines. Handbook of experimental pharmacology. 2011     [PubMed PMID: 20859806]
[8] Neumar RW,Otto CW,Link MS,Kronick SL,Shuster M,Callaway CW,Kudenchuk PJ,Ornato JP,McNally B,Silvers SM,Passman RS,White RD,Hess EP,Tang W,Davis D,Sinz E,Morrison LJ, Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2     [PubMed PMID: 20956224]
[9] Gowda RM,Khan IA,Mehta NJ,Vasavada BC,Sacchi TJ, Cardiac arrhythmias in pregnancy: clinical and therapeutic considerations. International journal of cardiology. 2003 Apr     [PubMed PMID: 12714190]