Adenosine

Adenosine is an antiarrhythmic agent belonging to Diagnostic Agent.

Adenosine is a medication used in myocardial perfusion scintigraphy and to treat supraventricular tachycardia.

Adenosine is rapidly taken up by an active transport system into erythrocytes and vascular endothelial cells. Rapidly metabolised intracellularly by adenosine kinase into adenosine monophosphate (AMP), and by adenosine deaminase into inosine. The plasma elimination half-life is approximately <10 seconds.

Adenosine shows common side effects like Chest discomfort; difficult or labored breathing; light-headedness or dizziness; throat, neck, or jaw discomfort; tightness in the chest.

Adenosine is available in the form of Injectable solution.

Adenosine is available in India, US, France, Italy, Germany, Japan, Russia, China and Singapore.

Adenosine belonging to the Diagnostic Agent, acts as an antiarrhythmic agent.

Antiarrhythmic actions: Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm.

Myocardial perfusion scintigraphy: Adenosine also causes coronary vasodilation and increases blood flow in normal coronary arteries with little to no increase in stenotic coronary arteries; thallium-201 uptake into the stenotic coronary arteries will be less than that of normal coronary arteries revealing areas of insufficient blood flow.

The Rapid onset of action achieved.

The Data of Duration of Action and Tmax of Adenosine is not available.

Adenosine is available in the form of Injectable solution.

Adenosine Injectable solution is given via intravenous route.

Adenosine is used to treat certain types of abnormal heartbeats. It is also used as a diagnostic aid during the stress test of the heart for patients who are unable to exercise adequately.

Adenosine is an antiarrhythmic agent belonging to Diagnostic Agent.

Adenosine is an endogenous purine nucleoside that is involved in numerous biological processes. It stimulates A₁ receptors to slow conduction time through the AV node; and A₂ receptors to produce peripheral and coronary vasodilation, thus, increasing blood flow in normal arteries w/ little to no increase in stenotic arteries.

Adenosine is approved for use in the following clinical indications

Adult indication

• Paroxysmal supraventricular tachycardia
• Pharmacologic stress testing

Although not approved, there have been certain off-label indications. These include

• Acute vasodilator testing in pulmonary artery hypertension
• Fractional flow reserve testing

Pediatric indication

• Supraventricular tachycardia

Adult Dose

• Paroxysmal supraventricular tachycardia

Initial: 6 mg; if not effective within 1 to 2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with 20 mL normal saline flush.

• Pharmacologic stress testing

IV: Continuous IV infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or volumetric infusion pump; total dose: 840 mcg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.

• Acute vasodilator testing in pulmonary artery hypertension

IV: Initial: 50 mcg/kg/minute increased by 50 mcg/kg/minute every 2 minutes to a maximum dose of 500 mcg/kg/minute or to a maximum dose of 350 mcg/kg/minute; acutely assess vasodilator response.

• Fractional flow reserve testing

IV: 140 mcg/kg/minute as a continuous infusion during testing.

Intracoronary: 40 mcg into the right coronary artery or 80 mcg into the left coronary artery; dilute dose in 10 mL of NS and administer rapidly through the guiding catheter.

Pediatric Dose

Supraventricular tachycardia

• Hemodynamically unstable:

Infants, Children, and Adolescents: Rapid IV, Intraosseous: Initial: 0.1 mg/kg (maximum initial dose: 6 mg/dose); if not effective, increase to 0.2 mg/kg (maximum dose: 12 mg/dose); follow each bolus with NS flush.

Hemodynamically stable:

Infants, Children, and Adolescents <50 kg: Rapid IV: Initial dose: 0.05 to 0.1 mg/kg via peripheral or central line; maximum initial dose: 6 mg/dose; if not effective within 1 to 2 minutes, increase dose by 0.05 to 0.1 mg/kg increments every 1 to 2 minutes to a maximum single dose of 0.3 mg/kg or 12 mg (whichever is less) or until termination of paroxysmal supraventricular tachycardia (PSVT); follow each bolus with NS flush.

Children and Adolescents ≥50 kg: Rapid IV: Initial: 6 mg via peripheral line, if not effective within 1 to 2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed; follow each bolus with NS flush.

Adenosine is available in various strengths as 25 mg/mL; 3 mg/mL; 300 mcg/50 mL-NaCl 0.9%; monophosphate; triphosphate; 50 mcg/mL-NaCl 0.9%; 1 mg/mL-NaCl 0.9%.

Adenosine is available in the form of Injectable solution.

Avoid consumption of caffeine (e.g. tea, coffee, chocolate, cola). Caffeine may antagonize the activity of adenosine.

Adenosine is contraindicated in patients with

• Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker).
• Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker).
• Known hypersensitivity to adenosine.

• Heart Block

Adenosine (adenosine injection) exerts its effect by decreasing conduction through the A-V node and may produce a short lasting first-, second- or third-degree heart block. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of Adenosine should not be given additional doses. Because of the very short half-life of adenosine, these effects are generally self-limiting. Appropriate resuscitative measures should be available. Transient or prolonged episodes of asystole have been reported with fatal outcomes in some cases. Rarely, ventricular fibrillation has been reported following Adenosine administration, including both resuscitated and fatal events. In most instances, these cases were associated with the concomitant use of digoxin and, less frequently with digoxin and verapamil. Although no causal relationship or drug-drug interaction has been established, Adenosine should be used with caution in patients receiving digoxin or digoxin and verapamil in combination.

• Arrhythmias at Time of Conversion

At the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the electrocardiogram. They generally last only a few seconds without intervention, and may take the form of premature ventricular contractions, atrial premature contractions, atrial fibrillation, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of A-V nodal block. Such findings were seen in 55% of patients.

• Bronchoconstriction

Adenosine (adenosine injection) is a respiratory stimulant (probably through activation of carotid body chemoreceptors) and intravenous administration in man has been shown to increase minute ventilation (Ve) and reduce arterial PCO₂ causing respiratory alkalosis. Adenosine administered by inhalation has been reported to cause bronchoconstriction in asthmatic patients, presumably due to mast cell degranulation and histamine release. These effects have not been observed in normal subjects. Adenosine has been administered to a limited number of patients with asthma and mild to moderate exacerbation of their symptoms has been reported. Respiratory compromise has occurred during adenosine infusion in patients with obstructive pulmonary disease. Adenosine should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis, etc.) and should be avoided in patients with bronchoconstriction or bronchospasm (e.g., asthma). Adenosine should be discontinued in any patient who develops severe respiratory difficulties.

Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. Because it is not known whether Adenosine can cause fetal harm when administered to pregnant women, Adenosine should be used during pregnancy only if clearly needed.

Avoid consumption of caffeine (e.g. tea, coffee, chocolate, cola). Caffeine may antagonise the activity of adenosine.

Common Adverse effects

• Cardiac arrhythmia, chest pressure, Headache, dizziness, Facial flushing, Gastrointestinal distress, Neck discomfort, Dyspnea.

Rare Adverse effects

• Atrioventricular block, depression of ST segment on ECG, hypotension, chest pain, palpitations, Nervousness, paresthesia, numbness, apprehension, Diaphoresis, Nausea, Upper extremity discomfort, Hyperventilation.

• Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents.
• Caffeine and Caffeine Containing Products: May diminish the therapeutic effect of Adenosine. Management: Monitor for decreased effect of adenosine if patient is receiving caffeine; significantly higher adenosine doses or alternative agents may be required. Discontinue caffeine 24 hours in advance of scheduled diagnostic use of adenosine if possible.
• Carbamazepine: May enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Monitor for increased degrees of heart block and bradycardia when these agents are combined. Consider using a lower initial dose of adenosine (3 mg) for the treatment of supraventricular tachycardia in patients who are receiving carbamazepine.
• Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy.
• Digoxin: May enhance the adverse/toxic effect of Adenosine.
• Dipyridamole: May enhance the adverse/toxic effect of Adenosine. Specifically, cardiovascular effects of adenosine may be enhanced. Adenosine dose reduction may be needed. Management: For patients requiring pharmacologic stress testing with adenosine, hold dipyridamole tablets for 48 hours. Hold aspirin/dipyridamole capsules for 24 to 48 hours. For treatment of SVT, monitor for prolonged adenosine effects, consider lower initial doses.
• Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole.
• Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose.
• Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine.
• Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
• Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents.
• Nicotine: May enhance the AV-blocking effect of Adenosine. Nicotine may enhance the tachycardic effect of Adenosine.
• Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents.
• Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm.
• Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring.
• Theophylline Derivatives: May diminish the therapeutic effect of Adenosine. Management: Consider alternatives to this combination if possible. Theophylline may decrease adenosine efficacy and higher adenosine doses may be required. When using adenosine for diagnostic studies, discontinue theophylline derivatives 5 half-lives prior to test.
• Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents.

The common side effects of Adenosine include the following

Common

● Chest discomfort; difficult or labored breathing; light-headedness or dizziness; throat, neck, or jaw discomfort; tightness in the chest.

Rare

● Chest pain, confusion, dizziness, faintness, or light-headedness when getting up suddenly from a lying or sitting position, Fainting, fast, slow, or irregular heartbeat, Sweating, troubled breathing, unusual tiredness or weakness, Fast, irregular, pounding, or racing heartbeat or pulse, headache, Nervousness, pounding in the ears.

• Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. Because it is not known whether Adenosine can cause fetal harm when administered to pregnant women, Adenosine should be used during pregnancy only if clearly needed.

• Nursing Mothers

Information is not available.

• Pediatric Use

The safety and effectiveness of Adenosine in patients less than 18 years of age have not been established.

• Geriatric Use

Clinical studies of Adenosine did not include enough subjects aged younger than 65 years to determine whether they respond differently. Other reported experience has not revealed clinically relevant differences of the response of elderly in comparison to younger patients. Greater sensitivity of some older individuals, however, cannot be ruled out.

The half-life of Adenosine (adenosine injection) is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting. Treatment of any prolonged adverse effects should be individualized and be directed toward the specific effect. Methylxanthines, such as caffeine and theophylline, are competitive antagonists of adenosine.

Pharmacodynamic

Adenosine is indicated as an adjunct to thallium-201 in myocardial perfusion scintigraphy and indicated for conversion of sinus rhythm of paroxysmal supraventricular tachycardia. Adenosine has a short duration of action as the half-life is <10 seconds, and a wide therapeutic window. Patients should be counselled regarding the risk of cardiovascular side effects, bronchoconstriction, seizures, and hypersensitivity.

Pharmacokinetics

• Absorption

Information is not available.

• Distribution

Rapidly taken up by an active transport system into erythrocytes and vascular endothelial cells.

• Metabolism and Excretion

Rapidly metabolized intracellularly by adenosine kinase into adenosine monophosphate (AMP), and by adenosine deaminase into inosine. The plasma elimination half-life is approximately <10 seconds.

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• https://www.rxlist.com/adenocard-drug.htm#indications
• https://reference.medscape.com/drug/adenocard-adenoscan-adenosine-342295
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• https://go.drugbank.com/drugs/DB00640
• https://www.uptodate.com/contents/adenosine-drug-information#F130654
• https://www.practo.com/medicine-info/adenosine-2080-api