Adenosine is an endogenous nucleoside occurring in all cells of the body. Adenosine is not chemically related to other antiarrhythmic drugs. Adenocard® (adenosine injection) is a sterile, nonpyrogenic solution for rapid bolus intravenous injection.
Mechanism of Action
Adenocard (adenosine injection) 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. Adenocard is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenocard is not blocked by atropine.
The intravenous bolus dose of 6 or 12 mg Adenocard (adenosine injection) usually has no systemic hemodynamic effects. When larger doses are given by infusion, adenosine decreases blood pressure by decreasing peripheral resistance.
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 Adenocard 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.
INDICATIONS AND USAGE:
Intravenous Adenocard (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 Adenocard administration.
It is important to be sure the Adenocard solution actually reaches the systemic circulation (see DOSAGE AND ADMINISTRATION).
Adenocard 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 Adenocard administration.
Intravenous Adenocard (adenosine injection) is contraindicated in:
1. Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker).
2. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients
with a functioning artificial pacemaker).
3. Known hypersensitivity to adenosine.
WARNINGS: Heart Block
Adenocard (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 Adenocard should not be given additional doses. Because of the very short half-life of adenosine, these effects are generally self-limiting.
Transient or prolonged episodes of asystole have been reported with fatal outcomes in some cases. Rarely, ventricular fibrillation has been reported following Adenocard 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, Adenocard should be used with
caution in patients receiving digoxin or digoxin and verapamil in combination. Appropriate resuscitative measures should be available.
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, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of A-V nodal block. Such findings were seen in 55% of patients.
Adenocard (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. Adenocard 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. Adenocard 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). Adenocard should be discontinued in any patient who develops severe respiratory difficulties.
PRECAUTIONS: Drug Interactions
Intravenous Adenocard (adenosine 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 Adenocard (see WARNINGS). Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, Adenocard should be used with caution in the presence of these agents. The use of Adenocard in patients receiving digitalis may be rarely associated with ventricular fibrillation (see WARNINGS).
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.
No controlled studies have been conducted in pediatric patients to establish the safety and efficacy of Adenocard 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 DOSAGE AND ADMINISTRATION)
Clinical studies of Adenocard 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, Adenocard 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.
The following reactions were reported with intravenous Adenocard (adenosine injection) 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%).
Also, in post-market clinical experience with Adenocard, cases of prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, atrial
fibrillation, and bronchospasm, in association with Adenocard use, have been reported (see
The half-life of Adenocard (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.
DOSAGE AND ADMINISTRATION:
For rapid bolus intravenous use only.
Adenocard® (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.
The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of Adenocard has not been systematically studied. The recommended intravenous doses for adults are as follows:
Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 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 a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.
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:
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.
Adenocard® (adenosine injection) is supplied as a sterile, non-pyrogenic solution in normal saline.
NDC 0469-8234-12 Product Code 823412 6 mg/2 mL (3 mg/mL) in a 2 mL (fill volume) Ansyr® plastic disposable syringe, in a package of ten.
NDC 0469-8234-14 Product Code 823414 12 mg/4 mL (3 mg/mL) in a 4 mL (fill volume) Ansyr® plastic disposable syringe, in a package of ten.
Store at controlled room temperature 15°- 30°C (59 °- 86°F).
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. Contains no preservatives. Discard unused portion.
Plastic syringes may require needle or blunt. To prevent needle-stick injuries, needles should not be recapped, purposely bent or broken by hand.
Wolff–Parkinson–White syndrome (WPW) is a disorder of the heart in which the ventricles of the heart contract prematurely due to an accessory pathway known as the bundle of Kent. This accessory pathway is an abnormal electrical communication from the atria to the ventricles. WPW is a type of atrioventricular reentrant tachycardia.
The incidence of WPW syndrome is between 0.1% and 0.3% of the general population.
While the majority of individuals with a bundle of Kent remain asymptomatic throughout their entire lives, there is a risk of sudden death associated with the syndrome. Sudden death due to WPW syndrome is rare (incidence of less than 0.6%), and is due to the accessory pathway disrupting the flow of electricity during tachyarrhythmias.
Capnography is the monitoring of the concentration or partial pressure of carbon dioxide (CO2) in the respiratory gases. Its main development has been as a monitoring tool for use during anaesthesia and intensive care. It is usually presented as a graph of expiratory CO2 plotted against time, or, less commonly, but more usefully, expired volume. The plot may also show the inspired CO2, which is of interest when rebreathing systems are being used.
The capnogram is a direct monitor of the inhaled and exhaled concentration or partial pressure of CO2, and an indirect monitor of the CO2 partial pressure in the arterial blood. In healthy individuals, the difference between arterial blood and expired gas CO2 partial pressures is very small. In the presence of most forms of lung disease, and some forms of congenital heart disease (the cyanotic lesions) the difference between arterial blood and expired gas increases and can exceed 1 kPa.
During anaesthesia, there is interplay between two components: the patient and the anaesthesia administration device (which is usually a breathing circuit and a ventilator). The critical connection between the two components is either an endotracheal tube or a mask, and CO2 is typically monitored at this junction. Capnography directly reflects the elimination of CO2 by the lungs to the anaesthesia device. Indirectly, it reflects the production of CO2 by tissues and the circulatory transport of CO2 to the lungs.
When expired CO2 is related to expired volume rather than time, the area beneath the curve represents the volume of CO2 in the breath, and thus over the course of a minute, this method can yield the CO2 minute elimination, an important measure of metabolism. Sudden changes in CO2 elimination during lung or heart surgery usually imply important changes in cardiorespiratory function.
Capnographs usually work on the principle that CO2 absorbs infra-red radiation. A beam of infra-red light is passed across the gas sample to fall on a sensor. The presence of CO2 in the gas leads to a reduction in the amount of light falling on the sensor, which changes the voltage in a circuit. The analysis is rapid and accurate, but the presence of nitrous oxide in the gas mix changes the infra-red absorption via the phenomenon of collision broadening. This must be corrected for. Measuring the CO2 in human breath by measuring its infra-red absorptive power was established as a reliable technique by John Tyndall in 1864, though 19th and early 20th century devices were too cumbersome for everyday clinical use.
Anaphylaxis is defined as “a serious allergic reaction that is rapid in onset and may cause death”. It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure. Common causes include insect bites, foods, and medications.
On a pathophysiologic level, anaphylaxis is due to the release of mediators from certain types of white blood cells triggered either by immunologic or non-immunologic mechanisms. It is diagnosed based on the presenting symptoms and signs. The primary treatment is injection of epinephrine, with other measures being complementary.
Acute Asthma (CLICK HERE)
An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness. While these are the primary symptoms of asthma, some people present primarily with coughing, and in severe cases, air motion may be significantly impaired such that no wheezing is heard.
Signs which occur during an asthma attack include the use of accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck), there may be a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation), and over-inflation of the chest. A blue color of the skin and nails may occur from lack of oxygen.
In a mild exacerbation the peak expiratory flow rate (PEFR) is ≥200 L/min or ≥50% of the predicted best. Moderate is defined as between 80 and 200 L/min or 25% and 50% of the predicted best while severe is defined as ≤ 80 L/min or ≤25% of the predicted best. Insufficient levels of vitamin D are linked with severe asthma attacks.