Adenosine

The administration of Adenosine for the treatment of PSVT follows a strict, standardized protocol to ensure the drug reaches the heart before it is metabolized by the blood. The American Heart Association (AHA) and the FDA-approved labeling recommend the following sequence for adult patients:

• Initial Dose: A 6 mg dose administered as a rapid intravenous bolus over 1 to 2 seconds.
• Second Dose: If the initial dose does not result in the elimination of the supraventricular tachycardia within 1 to 2 minutes, a 12 mg dose should be given as a rapid intravenous bolus.
• Third Dose: If the 12 mg dose does not work within 1 to 2 minutes, a final 12 mg dose may be administered.

For diagnostic stress testing, Adenosine is administered as a continuous intravenous infusion rather than a bolus. The standard dose is 140 mcg/kg/min infused over a period of six minutes, for a total dose of 0.84 mg/kg.

Adenosine is approved for use in pediatric patients, including neonates, for the conversion of PSVT. The dosage is based on the child's weight:

• Initial Dose: 0.05 to 0.1 mg/kg (maximum initial dose of 6 mg) given as a rapid IV bolus.
• Subsequent Doses: If the rhythm does not convert, the dose can be increased in increments of 0.05 to 0.1 mg/kg every 2 minutes until the rhythm converts or a maximum single dose of 0.2 mg/kg (or 12 mg) is reached.

Renal Impairment

No dosage adjustment is required for patients with renal impairment. Because Adenosine is cleared by cellular uptake and rapid metabolism in the blood, the kidneys do not play a significant role in its immediate clearance.

Hepatic Impairment

No dosage adjustment is required for patients with hepatic impairment. The liver is not the primary site of Adenosine metabolism.

Elderly Patients

Clinical studies have not identified significant differences in response between elderly and younger patients. However, healthcare providers exercise caution as older adults may have a higher prevalence of underlying heart disease or conduction abnormalities that could increase sensitivity to the drug.

Heart Transplant Patients

Patients who have received a heart transplant are known to be hypersensitive to Adenosine. In these individuals, the dose should be significantly reduced (often starting at 1 mg or 3 mg) to avoid prolonged periods of heart stoppage.

Adenosine is never self-administered; it is always given by a healthcare professional in a medical facility. The method of administration is critical to the drug's efficacy:

• Rapid IV Push: The drug must be injected as quickly as possible (1-2 seconds) into a large, proximal vein (like the antecubital fossa in the arm).
• Saline Flush: The injection must be followed immediately by a rapid flush of 20 mL of 0.9% sodium chloride (saline) to ensure the medication is pushed into the central circulation before it breaks down.
• Positioning: The patient is usually lying down, and the arm used for injection may be elevated to assist the drug's travel to the heart.
• Storage: Vials should be stored at room temperature (15°C to 30°C). Do not refrigerate, as crystallization may occur. If crystals form, they can be dissolved by warming the vial to room temperature.

Since Adenosine is administered by healthcare professionals in acute or diagnostic settings, missed doses in the traditional sense do not occur. If a procedure is delayed, the medical team will reschedule the administration based on clinical necessity.

Due to the extremely short half-life of Adenosine (less than 10 seconds), a true overdose is rare and usually self-limiting. However, an excessive dose could lead to:

• Prolonged heart block or asystole (heart stoppage).
• Severe hypotension (low blood pressure).
• Severe bronchoconstriction.

If symptoms of overdose occur, they typically resolve within seconds to a minute. In rare cases where symptoms persist, healthcare providers may administer competitive antagonists like caffeine or theophylline, although these are rarely necessary. Supportive care, including oxygen and temporary pacing, may be employed if needed.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance. The clinical team will monitor your response using an electrocardiogram (ECG) throughout the administration.

Adenosine is known for causing a brief but intense period of side effects immediately following the injection. While these are often alarming to the patient, they usually dissipate within 60 seconds due to the drug's rapid clearance. Common side effects include:

• Facial Flushing: A sudden feeling of warmth or redness in the face and neck, occurring in approximately 18% of patients.
• Dyspnea (Shortness of Breath): A feeling of being unable to catch one's breath or chest tightness, reported by about 12% of patients.
• Chest Pressure: A sensation often described as a 'heavy weight' on the chest or chest pain, occurring in 7% of patients. It is important to note that this is usually not related to a heart attack in this context.
• Nausea: A brief feeling of stomach upset or lightheadedness.

• Headache: A sharp or throbbing pain in the head that resolves quickly.
• Dizziness/Lightheadedness: A feeling of faintness as the heart rhythm changes.
• Sweating: Brief diaphoresis (sudden sweating).
• Palpitations: A sensation of the heart skipping a beat or pounding as it returns to a normal rhythm.
• Metallic Taste: Some patients report a brief, strange taste in their mouth.

• Blurred Vision: Temporary changes in sight.
• Hyperventilation: Rapid breathing triggered by the sensation of dyspnea.
• Urinary Urgency: A sudden, brief need to urinate.
• Tinnitus: Ringing in the ears.

While Adenosine is administered under medical supervision, certain reactions are considered emergencies that the clinical team is prepared to handle.

> Warning: Stop taking Adenosine and call your doctor immediately if you experience any of these symptoms, although in a clinical setting, your providers will be monitoring you for these events:

1. 1Prolonged Asystole: The heart may stop for a few seconds during the conversion of rhythm. If the heart does not restart spontaneously, it is a critical emergency.
2. 2Severe Bronchospasm: In patients with asthma or COPD, Adenosine can cause a severe tightening of the airways, making it impossible to breathe.
3. 3Ventricular Arrhythmias: Occasionally, the drug can trigger more dangerous heart rhythms, such as ventricular tachycardia or ventricular fibrillation.
4. 4Myocardial Infarction: In very rare cases, particularly during stress tests in patients with severe coronary artery disease, the drug may trigger a heart attack.
5. 5Anaphylaxis: A severe allergic reaction involving swelling of the throat, hives, and difficulty breathing.
6. 6Cerebrovascular Accident (Stroke): Transient ischemic attacks or strokes have been reported, particularly in association with the hemodynamic changes caused by the drug.

Because Adenosine is used for acute treatment or one-time diagnostic tests and has a half-life of seconds, there are no known 'long-term' side effects in the traditional sense (such as organ damage from chronic use). However, repeated administrations in a short period may lead to increased sensitivity or, conversely, a reduced response if the underlying condition is not addressed. Patients who have had a severe reaction to Adenosine should ensure this is noted in their permanent medical record to avoid future exposure.

As of 2026, Adenosine does not carry a traditional FDA 'Black Box' warning. However, the FDA-approved labeling contains 'Warnings' and 'Precautions' that are treated with the same level of clinical gravity. These include the risk of heart block, asystole, and the potential for fatal paradoxical airway constriction in patients with reactive airway disease.

Report any unusual symptoms to your healthcare provider immediately. Because the effects of Adenosine are so short-lived, most side effects will have passed by the time you can describe them, but it is vital to communicate exactly what you felt to your medical team.

Adenosine is a high-alert medication that must only be used in a setting with continuous cardiac monitoring and where emergency resuscitative equipment (including a defibrillator and airway management tools) is immediately available. The most important safety consideration is the drug's ability to cause a transient 'flatline' or asystole as it resets the heart rhythm. While this is usually brief, it requires expert supervision.

No FDA black box warnings for Adenosine. However, the drug carries significant warnings regarding its use in patients with certain heart and lung conditions.

• Heart Block and Asystole: Adenosine works by slowing the heart. In some patients, this can lead to high-grade heart block or a prolonged period where the heart does not beat. This is more common in patients with pre-existing conduction system disease.
• Bronchoconstriction/Asthma Risk: Adenosine is a potent bronchoconstrictor. It can trigger a severe asthma attack or respiratory distress in patients with asthma, chronic obstructive pulmonary disease (COPD), or other reactive airway diseases. Healthcare providers often avoid Adenosine in these patients, opting for alternative treatments.
• Proarrhythmic Potential: While it is used to stop arrhythmias, Adenosine can occasionally cause new ones, including atrial fibrillation or ventricular tachycardia. These are usually short-lived but may require medical intervention.
• Hypotension: The vasodilatory effects of Adenosine can cause a sudden drop in blood pressure. This is particularly dangerous in patients with autonomic dysfunction, stenotic valvular heart disease, or uncorrected hypovolemia (low blood volume).
• Hypersensitivity: Allergic reactions, including rash and anaphylaxis, have been reported. A history of allergy to Adenosine is a strict contraindication.

During and after the administration of Adenosine, the following monitoring is mandatory:

• Continuous ECG: A multi-lead electrocardiogram must be running to observe the heart's rhythm and the transition from tachycardia to sinus rhythm.
• Blood Pressure: Frequent or continuous blood pressure monitoring is required to detect sudden hypotension.
• Oxygen Saturation: Pulse oximetry is used to monitor respiratory status, especially in patients with a history of lung issues.
• Clinical Assessment: A healthcare provider will maintain constant verbal contact with the patient (if conscious) to assess for chest pain, shortness of breath, or neurological changes.

Patients should not drive or operate machinery immediately following the administration of Adenosine. While the drug clears the system quickly, the underlying condition (PSVT) or the stress of the diagnostic procedure can cause fatigue, dizziness, or emotional distress. Patients should wait until they are fully cleared by their physician, usually after a period of observation.

There is no direct chemical interaction between alcohol and Adenosine. However, alcohol can be a trigger for the very heart arrhythmias (like PSVT) that Adenosine is used to treat. Furthermore, alcohol can affect blood pressure and hydration status, potentially complicating the clinical picture during an emergency or stress test.

Adenosine is not a maintenance medication; therefore, there is no tapering requirement or withdrawal syndrome. It is a 'one-and-done' or 'as-needed' acute intervention.

> Important: Discuss all your medical conditions, especially any history of asthma, lung disease, or previous heart surgery, with your healthcare provider before starting Adenosine.

While there are few 'absolute' drug contraindications for a life-saving emergency like PSVT, certain drugs significantly alter Adenosine's effect:

• Dipyridamole (Persantine): This medication inhibits the cellular uptake of Adenosine. When a patient is taking dipyridamole, the effects of Adenosine are greatly potentiated (strengthened). The dose of Adenosine must be reduced by at least 75%, or the combination should be avoided entirely to prevent prolonged heart stoppage.

• Methylxanthines (Caffeine, Theophylline, Aminophylline): These substances are competitive antagonists of adenosine receptors. If a patient has significant levels of caffeine or theophylline in their blood, Adenosine may be completely ineffective. For diagnostic stress tests, patients are strictly instructed to avoid all caffeine for 12 to 24 hours prior to the procedure.
• Carbamazepine (Tegretol): This anticonvulsant may increase the degree of heart block produced by Adenosine. Using them together increases the risk of higher-degree AV block.
• Digoxin and Verapamil: When used in combination with Adenosine, these drugs (which also slow AV node conduction) may increase the risk of ventricular fibrillation or prolonged heart block.

• Nicotine: Smoking or nicotine replacement may increase the heart rate and potentially antagonize some of the effects of Adenosine, although this is less clinically significant than the interaction with caffeine.

• Caffeine: This is the most critical food interaction. Caffeine is found in coffee, tea, chocolate, many sodas, and 'non-drowsy' pain relievers. Caffeine molecules physically block the receptors that Adenosine needs to bind to. This can lead to a 'false negative' result in a stress test or a failure to convert an arrhythmia in an emergency.
• High-Fat Meals: While not a direct chemical interaction, heavy meals can affect the results of a cardiac stress test where Adenosine is used, as blood flow is diverted to the digestive system.

• Guarana: This herbal supplement contains high concentrations of caffeine and will antagonize the effects of Adenosine.
• Green Tea Extract: Similar to guarana, the caffeine content can interfere with the medication's efficacy.
• St. John's Wort: While primarily known for CYP450 interactions (which Adenosine does not use), it is generally advised to disclose all herbal use to the medical team.

Adenosine does not typically interfere with standard laboratory blood tests. However, its use during a myocardial perfusion scan (thallium or technetium) is specifically intended to alter the 'test' result to show blood flow patterns. It is also important to note that the presence of theophylline in the blood should be checked if a patient does not respond to standard Adenosine doses.

Mechanism of Interactions

Most Adenosine interactions occur at the receptor level. Methylxanthines (caffeine) have a similar molecular structure to Adenosine and 'sit' in the receptor, preventing Adenosine from entering. Dipyridamole, on the other hand, blocks the 'exit' or the transport system that takes Adenosine out of the blood and into cells, causing the drug to stay active in the bloodstream for much longer than intended.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially if you have consumed any caffeine in the last 24 hours.

Adenosine must NEVER be used in the following conditions due to the risk of fatal complications:

1. 1Second- or Third-Degree Heart Block: In these conditions, the electrical signal between the heart's upper and lower chambers is already impaired. Adenosine can completely stop the remaining electrical activity, leading to cardiac arrest. (Exception: Patients with a functioning artificial pacemaker).
2. 2Sick Sinus Syndrome: This is a dysfunction of the heart's natural pacemaker. Adenosine can cause a prolonged failure of the heart to restart after the injection. (Exception: Patients with a functioning artificial pacemaker).
3. 3Known Hypersensitivity: Any previous allergic reaction to Adenosine or its components is an absolute contraindication.
4. 4Symptomatic Bradycardia: If a patient already has a dangerously slow heart rate, Adenosine will worsen the condition significantly.

In these conditions, healthcare providers must perform a careful risk-benefit analysis:

• Asthma and COPD: Because Adenosine can cause bronchospasm, it is generally avoided in patients with reactive airway disease. If it must be used, medical teams must be prepared to treat a severe asthma attack immediately.
• Unstable Angina: In diagnostic settings, Adenosine may cause a 'steal' of blood flow from already compromised heart muscle, potentially worsening chest pain or causing a heart attack.
• Heart Transplant: As mentioned, these patients are extremely sensitive to Adenosine and require much lower doses.
• Cerebrovascular Disease: Patients with significant blockages in the arteries to the brain may be at higher risk for stroke due to the brief drop in blood pressure caused by the drug.

There is no known cross-sensitivity between Adenosine and other classes of antiarrhythmics like beta-blockers or calcium channel blockers. However, patients who have had adverse reactions to ATP (Adenosine Triphosphate) injections may also react to Adenosine.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of 'fainting spells' or lung disease, before prescribing Adenosine.

Adenosine is classified as FDA Pregnancy Category C. There have been no adequate and well-controlled studies in pregnant women to determine its safety. However, because Adenosine is a naturally occurring substance in the body and has an extremely short half-life (seconds), it is often the preferred agent for treating PSVT in pregnant women when non-pharmacological measures (like the Valsalva maneuver) fail.

• First Trimester: Caution is always advised during organogenesis, but maternal stability is paramount for fetal health.
• Labor and Delivery: Adenosine has been used during labor without reported ill effects on the newborn.
• Teratogenicity: Animal studies have not been conducted, but the rapid clearance suggests a low risk of fetal exposure.

It is not known whether Adenosine is excreted in human milk. However, given that the drug is cleared from the systemic circulation within seconds, it is highly unlikely that any significant amount would reach the breast milk or be absorbed by a nursing infant. Most clinical guidelines suggest that breastfeeding does not need to be interrupted following the administration of Adenosine.

Adenosine is widely used and considered safe and effective for the treatment of PSVT in pediatric patients, including infants and neonates.

• Dosing: Pediatric dosing is weight-based (typically 0.1 mg/kg).
• Efficacy: Success rates for converting SVT in children are similar to those in adults.
• Safety: The side effect profile in children is similar to adults, with flushing and brief dyspnea being the most common reports.

Elderly patients (aged 65 and older) may be more sensitive to the effects of Adenosine.

• Conduction Disease: Older adults are more likely to have underlying sinus node dysfunction or AV block, increasing the risk of prolonged asystole.
• Polypharmacy: The elderly are more likely to be taking medications like digoxin or verapamil, which can interact with Adenosine.
• Dosing: While no formal dose reduction is mandated, clinicians often start at the lower end of the dosing range and monitor more closely.

As Adenosine is not cleared by the kidneys, no dosage adjustments are necessary for patients with renal failure or those on dialysis. The drug is effectively removed from the blood by cellular uptake regardless of kidney function.

Since the liver is not the primary site of metabolism for Adenosine, patients with liver cirrhosis or hepatic failure do not require dose adjustments. The rapid deamination of Adenosine occurs in the blood and vascular endothelium.

> Important: Special populations require individualized medical assessment. Always inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding before any medical procedure involving Adenosine.

Adenosine is an endogenous purine nucleoside that modulates various physiological processes through four known G-protein-coupled receptors: A1, A2A, A2B, and A3. Its antiarrhythmic effect is primarily mediated by the A1 receptor in cardiac nodal tissue. Activation of the A1 receptor inhibits adenylyl cyclase, decreasing cAMP, and leads to the activation of $I_{K,Ado}$ (an inward-rectifying potassium current). This causes hyperpolarization of the cell membrane and shortens the action potential duration, specifically in the AV node. This 'stuns' the conduction system, breaking re-entrant circuits.

Its diagnostic effect is mediated by the A2A receptor in the coronary vascular smooth muscle. Activation of A2A receptors stimulates adenylyl cyclase, increasing cAMP levels, which leads to protein kinase A activation and the opening of ATP-sensitive potassium channels. This results in smooth muscle relaxation and significant vasodilation.

• Onset of Action: Immediate. The effect on the heart rhythm is usually seen within 10 to 30 seconds of a rapid IV bolus.
• Duration of Effect: Less than 1 minute. The heart rhythm usually stabilizes or returns to its previous state (if conversion fails) within 60 seconds.
• Tolerance: No tolerance develops, as the drug is used for acute, short-term intervention.

| Parameter | Value |

|---|---|

| Bioavailability | 100% (IV administration) |

| Protein Binding | Negligible (<5%) |

| Half-life | < 10 seconds |

| Tmax | Immediate (seconds) |

| Metabolism | Cellular uptake; Deamination to Inosine; Phosphorylation to AMP |

| Excretion | Not applicable (metabolized in blood/tissues) |

• Molecular Formula: $C_{10}H_{13}N_{5}O_{4}$
• Molecular Weight: 267.24 g/mol
• Solubility: Slightly soluble in water; soluble in hot water.
• Structure: Consists of an adenine molecule attached to a ribose sugar molecule (ribofuranose) via a $\beta$-N9-glycosidic bond.

Adenosine is the prototype of the Adenosine Receptor Agonist [EPC] class. While it is an antiarrhythmic, it does not fit neatly into the traditional Vaughan-Williams classification (which includes Class I-IV), though it is sometimes grouped with Class V or 'miscellaneous' antiarrhythmics. Related medications include Regadenoson (Lexiscan), which is a selective A2A agonist used for stress testing but lacks Adenosine's antiarrhythmic properties.