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Adenosine
Overview
What is Adenosine?
Adenosine is an endogenous nucleoside occurring in all cells of the body. It is chemically 6-amino-9-ß-D-ribofuranosyl-9-H-purine and has the following structural formula:
Adenosine is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH. Adenosine is not chemically related to other antiarrhythmic drugs. Adenosine injection is a sterile, nonpyrogenic solution for rapid bolus intravenous injection. Each mL contains 3 mg adenosine and 9 mg sodium chloride in Water for Injection. The pH of the solution is between 4.5 and 7.5.
What does Adenosine look like?
What are the available doses of Adenosine?
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What should I talk to my health care provider before I take Adenosine?
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How should I use Adenosine?
Intravenous adenosine injection is indicated for the following:
Conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver), should be attempted prior to adenosine administration.
It is important to be sure the adenosine solution actually reaches the systemic circulation (see ).
Adenosine does not convert atrial flutter, atrial fibrillation, or ventricular tachycardia to normal sinus rhythm. In the presence of atrial flutter or atrial fibrillation, a transient modest slowing of ventricular response may occur immediately following adenosine administration.
For rapid bolus intravenous use only.
Adenosine injection should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the systemic circulation, it should be administered either directly into a vein or, if given into an IV line, it should be given as close to the patient as possible and followed by a rapid saline flush.
What interacts with Adenosine?
- Intravenous adenosine injection 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 adenosine.
What are the warnings of Adenosine?
Heart Block
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 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 PCO 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.
What are the precautions of Adenosine?
Drug Interactions
Intravenous adenosine 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 adenosine (see ). Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, adenosine should be used with caution in the presence of these agents. The use of adenosine in patients receiving digitalis may be rarely associated with ventricular fibrillation (see ).
The effects of adenosine are antagonized by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective. Adenosine effects are potentiated by dipyridamole. Thus, smaller doses of adenosine may be effective in the presence of dipyridamole. Carbamazepine has been reported to increase the degree of heart block produced by other agents. As the primary effect of adenosine is to decrease conduction through the A-V node, higher degrees of heart block may be produced in the presence of carbamazepine.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies in animals have not been performed to evaluate the carcinogenic potential of adenosine. Adenosine was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.
Adenosine, however, like other nucleosides at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety of chromosomal alterations. Fertility studies in animals have not been conducted with adenosine.
Pregnancy Category C
Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since 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.
Pediatric Use
No controlled studies have been conducted in pediatric patients to establish the safety and efficacy of adenosine for the conversion of paroxysmal supraventricular tachycardia (PSVT). However, intravenous adenosine has been used for the treatment of PSVT in neonates, infants, children and adolescents (see ).
Geriatric Use
Clinical studies of adenosine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, adenosine in geriatric patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter hemodynamic function and produce severe bradycardia or AV block.
What are the side effects of Adenosine?
The following reactions were reported with intravenous adenosine used in controlled U.S. clinical trials. The placebo group had a less than 1% rate of all of these reactions.
Cardiovascular
Facial flushing (18%), headache (2%), sweating,palpitations, chest pain, hypotension (less than 1%).
Respiratory
Shortness of breath/dyspnea (12%), chest pressure(7%), hyperventilation, head pressure (less than 1%).
Central Nervous System
Lightheadedness (2%), dizziness, tingling in arms,numbness (1%), apprehension, blurred vision, burningsensation, heaviness in arms, neck and back pain (lessthan 1%).
Gastrointestinal
Nausea (3%), metallic taste, tightness in throat,pressure in groin (less than 1%).
Post Marketing Experience
(see )
The following adverse events have been reported from marketing experience with adenosine. Because these events are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these events in labeling are typically based on one or more of the following factors: (1) seriousness of the event, (2) frequency of the reporting, (3) strength of causal connection to the drug, or a combination of these factors.
Prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, atrial fibrillation, and Torsade de Pointes.
Bronchospasm
Seizure activity, including tonic clonic (grand mal) seizures, and loss of consciousness.
What should I look out for while using Adenosine?
Intravenous adenosine injection is contraindicated in:
What might happen if I take too much Adenosine?
The half-life of 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.
How should I store and handle Adenosine?
Procedures for proper handling and disposal should be considered. Consideration should be given to handling and disposal according to guidelines issued for cytotoxic drugs. Several guidelines on this subject have been published. Caution should be exercised in the handling and preparation of Fludarabine Phosphate Injection solution. The use of latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If the solution contacts the skin or mucous membranes, wash thoroughly with soap and water; rinse eyes thoroughly with plain water. Avoid exposure by inhalation or by direct contact of the skin or mucous membranes.Adenosine injection is supplied as a sterile, nonpyrogenic solution in normal saline.NDC 10019-063-03 6 mg/2 mL (3 mg/mL) in 2 mL flip-top vials, packaged in shelf packs of ten.NDC 10019-063-08 6 mg/2 mL (3 mg/mL) in a 2 mL disposable glass syringe, packaged in shelf packs of ten.Adenosine injection is supplied as a sterile, nonpyrogenic solution in normal saline.NDC 10019-063-03 6 mg/2 mL (3 mg/mL) in 2 mL flip-top vials, packaged in shelf packs of ten.NDC 10019-063-08 6 mg/2 mL (3 mg/mL) in a 2 mL disposable glass syringe, packaged in shelf packs of ten.Adenosine injection is supplied as a sterile, nonpyrogenic solution in normal saline.NDC 10019-063-03 6 mg/2 mL (3 mg/mL) in 2 mL flip-top vials, packaged in shelf packs of ten.NDC 10019-063-08 6 mg/2 mL (3 mg/mL) in a 2 mL disposable glass syringe, packaged in shelf packs of ten.
