What is the purpose of Adenosine (adenosine)?

From the Guidelines

Adenosine is a rapid-acting cardiovascular medication primarily used to treat paroxysmal supraventricular tachycardia (PSVT), with a recommended initial dose of 6 mg given as a rapid IV bolus over 1-2 seconds, followed by a saline flush, as supported by the 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia 1. The standard adult dosing begins with 6 mg given as a rapid IV bolus over 1-2 seconds, followed by a saline flush. If the first dose is ineffective after 1-2 minutes, a 12 mg dose can be administered, which may be repeated once more if necessary. For pediatric patients, the initial dose is 0.1 mg/kg (maximum 6 mg), followed by 0.2 mg/kg (maximum 12 mg) if needed. Adenosine works by temporarily blocking AV node conduction, interrupting reentry circuits and restoring normal sinus rhythm. Common side effects include:

• Flushing
• Chest pain
• Dyspnea
• Transient arrhythmias though these typically resolve within seconds due to adenosine's extremely short half-life of less than 10 seconds. Important contraindications include:
• Second or third-degree heart block (without a pacemaker)
• Sick sinus syndrome
• Atrial fibrillation or flutter with accessory pathway conduction
• Hypersensitivity to adenosine The drug interacts with:
• Dipyridamole (which potentiates adenosine effects)
• Methylxanthines like caffeine and theophylline (which antagonize adenosine) Patients should be monitored with continuous ECG during administration, and resuscitation equipment should be immediately available due to the potential for transient high-grade heart block, as recommended by the 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

1. 1 Mechanism of Action Adenosine causes cardiac vasodilation which increases cardiac blood flow. Adenosine is thought to exert its pharmacological effects through activation of purine receptors (cell-surface A1 and A2 adenosine receptors) Although the exact mechanism by which adenosine receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A2 receptors in smooth muscle cells. Adenosine may also lessen vascular tone by modulating sympathetic neurotransmission The intracellular uptake of adenosine is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, adenosine is rapidly phosphorylated by adenosine kinase to adenosine monophosphate, or deaminated by adenosine deaminase to inosine. These intracellular metabolites of adenosine are not vasoactive Myocardial uptake of thallium-201 is directly proportional to coronary blood flow. Since adenosine injection significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, adenosine injection causes relatively less thallium-201 uptake in vascular territories supplied by stenotic coronary arteries i.e., a greater difference is seen after adenosine injection between areas served by normal and areas served by stenotic vessels than is seen prior to adenosine injection.
2. 2 Pharmacodynamics Hemodynamic Effects Adenosine produces a direct negative chronotropic, dromotropic and inotropic effect on the heart, presumably due to A1-receptor agonism, and produces peripheral vasodilation, presumably due to A2-receptor agonism The net effect of adenosine injection in humans is typically a mild to moderate reduction in systolic, diastolic and mean arterial blood pressure associated with a reflex increase in heart rate. Rarely, significant hypotension and tachycardia have been observed [see Warnings and Precautions ( 5-5.4)].
3. 3 Pharmacokinetics Distribution Intravenously administered adenosine distributes from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical Metabolism Intracellular adenosine is metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol. Since adenosine kinase has a lower Km and Vmax than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool Elimination While extracellular adenosine is primarily cleared from plasma by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of adenosine deaminase

The adenosine drug card is summarized as follows:

• Indications: Adenosine injection is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately 2.
• Mechanism of Action: Adenosine causes cardiac vasodilation, which increases cardiac blood flow, by activating purine receptors (A1 and A2 adenosine receptors) 2.
• Pharmacodynamics: Adenosine produces a direct negative chronotropic, dromotropic, and inotropic effect on the heart and peripheral vasodilation 2.
• Pharmacokinetics: Adenosine is rapidly metabolized by adenosine kinase and adenosine deaminase, with a half-life of less than 10 seconds in whole blood 2.
• Contraindications: Adenosine injection is contraindicated in patients with second- or third-degree AV block, sinus node disease, known or suspected bronchoconstrictive or bronchospastic lung disease, and known hypersensitivity to adenosine injection 2.
• Warnings and Precautions: Adenosine injection can cause cardiac arrest, ventricular arrhythmias, and myocardial infarction, as well as bronchoconstriction, hypotension, and cerebrovascular accidents 2.
• Adverse Reactions: The most common adverse reactions to adenosine injection are flushing, chest discomfort, shortness of breath, headache, and dizziness 2.
• Dosage and Administration: The recommended dose of adenosine injection is 0.14 mg/kg/min infused over six minutes as a continuous peripheral intravenous infusion 2.

From the Research

Adenosine Drug Card

• Indications: Adenosine is used for the treatment of supraventricular tachycardia (SVT) in adults, particularly when vagal maneuvers fail 3, 4, 5.
• Mechanism of Action: Adenosine works by slowing conduction through the atrioventricular node, thereby terminating SVT 3.
• Efficacy: Adenosine is effective in converting SVT to sinus rhythm, with a success rate comparable to that of calcium channel antagonists 3, 6.
• Side Effects: Adenosine can cause minor adverse events such as nausea, chest tightness, shortness of breath, and headache, which are reported more frequently than with calcium channel antagonists 3, 6.
• Comparison to Calcium Channel Antagonists: Adenosine and calcium channel antagonists have similar efficacy in treating SVT, but adenosine may have a higher incidence of minor side effects 3, 6.
• Administration: Adenosine is typically administered as a rapid intravenous bolus, with a dose of 6 mg followed by 12 mg if necessary 7.
• Alternative Therapies: Other treatments for SVT include vagal maneuvers, beta-blockers, and catheter ablation 4, 5.
• Patient Education: Patients should be informed of the potential risks and benefits of adenosine treatment, including the possibility of minor side effects 3.