Adenine Deoxyribonucleoside

Uses

Intravenous Adenine Deoxyribonucleoside is used for the following: Conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome).

Adenine Deoxyribonucleoside is also used to associated treatment for these conditions: Paroxysmal Supraventricular Tachycardia, SVT, Tachycardia, Supraventricular, Symptomatic pulmonary arterial hypertension (PAH)

How Adenine Deoxyribonucleoside works

Agonism of adenosine receptors A1 and A2 reduces conduction time in the atrioventricular node of the heart. Conduction time is decreased by inducing potassium efflux and inhibiting calcium influx through channels in nerve cells, leading to hyperpolarization and and increased threshold for calcium dependent action potentials. Decreased conduction time leads to an antiarrhythmic effect. Inhibition of calcium influx, reduces the activity of adenylate cyclase, relaxing vascular smooth muscle. Relaxed vascular smooth muscle leads to increased blood flow through normal coronary arteries but not stenotic arteries, allowing thallium-201 to be more readily uptaken in normal coronary arteries.

Dosage

Adenine Deoxyribonucleoside dosage

Adult:

Initial dose: 6 mg given as rapid IV bolus (administered over 1-2 second period).

Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1-2 minutes, 12 mg should be given as rapid intravenous bolus. This 12 mg dose may be repeated for second time if required.

Pediatric:

The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis.

• Body weight < 50 kg: Initial dose - 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.
• Body weight > 50 kg: The adult dose is recommended. Doses greater than 12 mg are not recommended for adult and pediatric patients

Repeat administration: If conversion of PSVT does not occur within 1-2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. A saline flush should follow. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.

Side Effects

Cardiovascular: Facial flushing, headache, sweating, palpitations, chest pain, hypotension. Respiratory: Shortness of breath/dyspnea, chest pressure, hyperventilation, head pressure.

Central Nervous System: Lightheadedness, dizziness, tingling in arms, numbness, apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain.

Gastrointestinal: Nausea, metallic taste, tightness in throat, pressure in groin. In post-market clinical experience with Adenine Deoxyribonucleoside, cases of prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, hypotension, atrial fibrillation and bronchospasm, in association with Adenine Deoxyribonucleoside use, have been reported.

Toxicity

Patients experiencing an overdose of adenosine may present with asystole, heart block, or cardiac ischemia; though the effects are generally short lived. Patients experiencing an overdose should be treated with symptomatic and supportive care, which may include a slow intravenous injection of theophylline.

The LD₅₀ in mice is >20 g/kg subcutaneously, 500mg/kg intraperitoneally, and 39.6 µg/kg subcutaneously.[L32048]

Interaction

Intravenous Adenine Deoxyribonucleoside injection has been effectively administered in the presence of other cardioactive drugs, such as Quinidine, beta- adrenergic blocking agents, Calcium channel blocking agents and angiotensin converting enzyme inhibitors without any change in the adverse reaction profile. Digoxin and Verapamil use may be rarely associated with ventricular fibrillation when combined with Adenine Deoxyribonucleoside. Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, Adenine Deoxyribonucleoside should be used with caution in the presence of these agents. The use of Adenine Deoxyribonucleoside in patients receiving Digitalis may be rarely associated with ventricular fibrillation. The effects of Adenine Deoxyribonucleoside are antagonized by Methylxanthines, such as, Caffeine and Theophylline.

Food Interaction

• Avoid caffeine. Caffeine may antagonise the activity of adenosine.

[Moderate] ADJUST DOSING INTERVAL: Caffeine and other xanthine derivatives (e.g., theophylline) are nonspecific, competitive antagonists of adenosine receptors and may interfere with the hemodynamic effects of adenosine.

There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia.

In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain
MANAGEMENT: Clinicians should be aware that adenosine may be less effective in the presence of xanthine derivatives including caffeine.

Patients should avoid consumption of caffeine-containing products for at least 12 hours, preferably 24 hours, prior to administration of adenosine for myocardial perfusion imaging.

Adenine Deoxyribonucleoside Drug Interaction

Moderate: ondansetron, ondansetronUnknown: aspirin, aspirin, charcoal, charcoal, epinephrine, epinephrine, lorazepam, lorazepam, diltiazem, diltiazem, glucose, glucose, furosemide, furosemide, acetaminophen, acetaminophen, midazolam, midazolam

Adenine Deoxyribonucleoside Disease Interaction

Major: AV node dysfunction, cardiovascular dysfunction, proarrhythmic effectsModerate: bronchoconstriction

Volume of Distribution

Data regarding the volume of distribution of adenosine are not readily available.

Elimination Route

Data regarding the absorption of adenosine are not readily available.

Half Life

The half life of adenosine in blood is less than 10 seconds.

Clearance

Data regarding the clearance of adenosine are not readily available.

Elimination Route

Adenine Deoxyribonucleoside is predominantly eliminated in the urine as uric acid.

Pregnancy & Breastfeeding use

US FDA pregnancy category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Contraindication

Intravenous Adenine Deoxyribonucleoside is contraindicated in:

• 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 Adenine Deoxyribonucleoside.

Acute Overdose

The half-life of Adenine Deoxyribonucleoside 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 Adenine Deoxyribonucleoside.

Storage Condition

Store in cool dry place protected from light. Keep out of reach of children. Do not refrigerate as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.

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