Adenosine: Difference between revisions
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|PK= | |PK=[[Intravenous]]ly administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by [[erythrocyte]]s and vascular [[endothelial cell]]s. This process involves a specific [[transmembrane]] [[nucleoside]] carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. [[Intracellular]] adenosine is rapidly 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 [[cytosol]]ic 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. While [[extracellular]] adenosine is primarily cleared by cellular uptake with a [[half-life]] of less than 10 seconds in whole blood, excessive amounts may be [[deamination|deaminated]] by an ecto-form of [[adenosine deaminase]]. As adenosine requires no [[hepatic]] or [[renal]] function for its activation or inactivation, [[hepatic]] and [[renal]] failure would not be expected to alter its effectiveness or tolerability. | ||
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Revision as of 05:39, 14 May 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shankar Kumar, MBBS [2]
Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
Overview
Adenosine is an Antiarrhythmic that is FDA approved for the {{{indicationType}}} of paroxysmal supraventricular tachycardia (PSVT). Common adverse reactions include facial flushing (18%), shortness of breath/ dyspnea (12%), chest pressure (7%), and nausea (3%).
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Paroxysmal Supraventricular Tachycardia
- Dosing Information
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.
- Initial dose: Adenosine 6 mg given as a rapid intravenous bolus (administered over a 1 to 2 second period).
- Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, Adenosine 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.
Doses greater than 12 mg are not recommended for adult patients.
NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Non–Guideline-Supported Use
Condition 1
- Dosing Information
- (Dosage)
Condition 2
- Dosing Information
- (Dosage)
Condition 3
- Dosing Information
- (Dosage)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Paroxysmal Supraventricular Tachycardia
- Dosing Information
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis.
Pediatric Patients with a Body Weight < 50 kg:
- Initial dose: Give Adenosine 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.
- Repeat administration: If conversion of PSVT does not occur within 1 to 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. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.
Pediatric Patients with a Body Weight ≥ 50 kg:
- Administer the adult dose.
Doses greater than 12 mg are not recommended for pediatric patients.
NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition 1
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Condition 2
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
Non–Guideline-Supported Use
Condition 1
- Dosing Information
- (Dosage)
Condition 2
- Dosing Information
- (Dosage)
Condition 3
- Dosing Information
- (Dosage)
Contraindications
- 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.
Warnings
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 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.
Adverse Reactions
Clinical Trials Experience
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, burning sensation, heaviness in arms, neck and back pain (less than 1%).
Gastrointestinal
- Nausea (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).
Postmarketing Experience
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.
Cardiovascular
- Prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, atrial fibrillation, and Torsade de Pointes.
Respiratory
- Bronchospasm
Central Nervous System
- Seizure activity, including tonic clonic (grand mal) seizures, and loss of consciousness.
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. 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.
- 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.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): 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.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Adenosine during labor and delivery.
Nursing Mothers
There is no FDA guidance on use of Adenosine during nursing.
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.
Geriatic 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.
Gender
There is no FDA guidance on use of Adenosine with respect to specific gender.
Race
There is no FDA guidance on use of Adenosine with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on use of Adenosine in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on use of Adenosine in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on use of Adenosine in females of reproductive potential and males.
Immunocompromised Patients
There is no FDA guidance on use of Adenosine in patients who are immunocompromised.
Others
(Description)
Administration and Monitoring
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.
- Adult Patients
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of adenosine has not been systematically studied.
Initial dose is given as a rapid intravenous bolus (administered over a 1 to 2 second period). If the first dose does not result in elimination of the supraventricular tachycardia within 1 to 2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.
- Pediatric Patients
The dosages used in neonates, infants, children and adolescents were equivalent to those administered to adults on a weight basis. For pediatric patients with a body weight < 50 kg, an initial dose of 0.05 to 0.1 mg/kg as a rapid IV bolus is given either centrally or peripherally. A saline flush should follow. If conversion of PSVT does not occur within 1 to 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. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used. For pediatric patients with a body weight ≥ 50 kg, administer the adult dose.
Doses greater than 12 mg are not recommended for adult and pediatric patients.
NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.
Monitoring
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 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.
IV Compatibility
There is limited information about the compatibility of Adenosine and IV administrations.
Overdosage
Acute Overdose
The half-life of adenosine injection is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting.
Management
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. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
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Adenosine
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| Systematic (IUPAC) name | |
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| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | ? |
| Chemical data | |
| Formula | ? |
| Mol. mass | ? |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
Mechanism of Action
Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the A-V node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome.
Adenosine is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenosine is not blocked by atropine.
Structure
(Description with picture)
Pharmacodynamics
(Description)
Pharmacokinetics
Intravenously administered adenosine is rapidly cleared 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. Intracellular adenosine is rapidly 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. While extracellular adenosine is primarily cleared 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. As adenosine requires no hepatic or renal function for its activation or inactivation, hepatic and renal failure would not be expected to alter its effectiveness or tolerability.
Nonclinical Toxicology
(Description)
Clinical Studies
Condition 1
(Description)
Condition 2
(Description)
Condition 3
(Description)
How Supplied
(Description)
Storage
There is limited information regarding Adenosine Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Adenosine |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Adenosine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
(Patient Counseling Information)
Precautions with Alcohol
Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Adenosine Brand Names in the drug label.
Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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