Adenosine

Cosmetic ingredients (Adenosine) -> CIR (Cosmetic Ingredient Review)

Skin conditioning

log Kow = -1.05

-1.05

Needles (from water +3/2)

Crystals from water

White crystalline powder

Water solubility increases by warming and lowering the pH

Insoluble in ethanol

In water, 5.1 g/L at 25 °C

37 mg/mL

>40.1 [ug/mL] (The mean of the results at pH 7.4)

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

235.5 °C

235.5 °C

This chemical does not meet GHS hazard criteria for 77.4% (120 of 155) of all reports.

Warning

H315 (21.9%): Causes skin irritation [Warning Skin corrosion/irritation]

P264, P264+P265, P280, P302+P352, P305+P351+P338, P321, P332+P317, P337+P317, and P362+P364 (click each P-code to see the statement)

Aggregated GHS information provided per 155 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Chemical: Adenosine

Status: Active Update: 18-04-2023 https://echa.europa.eu/registration-dossier/-/registered-dossier/23062

Dehydran 240: Does not have an individual approval but may be used under an appropriate group standard

Adenosine: Does not have an individual approval but may be used under an appropriate group standard

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl adenosine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Residues of adenosine are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Synergist. Limit: Maximum of 0.5% of formulation.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Residues of adenosine are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Synergist. Limit: Maximum of 0.5% of formulation.

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.

The adverse effects of adenosine are secondary to the activation of adenosine receptors found on vascular tissue, causing vasodilation. Symptoms of skin flushing, lightheadedness, nausea, sweating, nervousness, numbness, and a feeling of impending doom have all been described; however, these effects are very transient and short-lived secondary to adenosine’s short half-life.

Safe in the present practices of use and concentration. Ingredient, concentration, and use information are available in documents discoverable at https://cir-reports.cir-safety.org

Due to the rapidly short half-life of adenosine, the toxic effects of adenosine are kept to a minimum. However, there have been reports of severe effects involving prolonged asystole, development of heart block, and cardiac ischemia with adenosine. Unless the patient sustains a permanent injury, these effects are transient, and patients should receive appropriate supportive measures.

Adenosine slows conduction time through the AV node and can interrupt the reentry pathways through the AV node, resulting in the restoration of normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome. This effect may be mediated through the drug's activation of cell-surface A₁ and A₂ adenosine receptors. Adenosine also inhibits the slow inward calcium current and activation of adenylate cyclase in smooth muscle cells, thereby causing relaxation of vascular smooth muscle. By increasing blood flow in normal coronary arteries with little or no increase in stenotic arteries (with little to no increase in stenotic arteries), adenosine produces a relative difference in thallous (thallium) chloride TI 201 uptake in myocardium supplied by normal verus stenotic coronary arteries.

/HUMAN EXPOSURE STUDIES/ Chronic heart failure (CHF) is accompanied by increased adenosine plasma levels (APLs). It is unknown whether adenosine release occurs at the peripheral level or whether the myocardium itself is the source of adenosine release. To answer this question, we evaluated APLs in the coronary sinus of CHF patients during a resynchronisation procedure and compared the values with those at the peripheral level. /The authors/ also investigated a possible correlation between APLs and ischaemia-modified albumin (IMA) levels, a useful marker of tissue ischaemia. ... 19 men and seven women were prospectively included. Blood samples for APLs were collected simultaneously from a brachial vein (peripheral) and from the coronary sinus. Blood samples for brain natriutretic peptide (BNP) and IMA were collected from a brachial vein. ... APLs from the brachial vein were higher than those from the coronary sinus (1.69 vs 0.75 muM p<0.01). IMA levels were correlated with APLs from the brachial vein (r = 0.59, p<0.01). BNP concentrations were correlated with APLs from the brachial vein (r = 0.73, p<0.001) but not with APLs from the coronary sinus (r = 0.38, p>0.05). BNP concentrations and IMA levels were correlated (r = 0.71, p<0.001). ...

/HUMAN EXPOSURE STUDIES/ ... /The authors/ compared the effects of 10 mg of intravenous adenosine with placebo in 21 normal subjects under normoxic conditions and evaluated the temporal sequence of the effects of adenosine on ventilation, dyspnea, and heart rate. The study was repeated in 11 of these subjects during hyperoxia. In all subjects, adenosine resulted in the development of dyspnea, assessed by handgrip dynamometry, without any significant change (p > 0.1) in lung resistance as measured by the interrupter technique. There were significant increases (p < 0.05) in ventilation and heart rate in response to adenosine. The dyspneic response occurred slightly before the ventilatory or heart rate responses in every subject, but the timing of the dyspneic, ventilatory, and heart rate responses was not significantly different when the group data were analyzed (18.9 +/- 5.8, 20.3 +/- 5.5, and 19.7 +/- 4.5 s, respectively). During hyperoxia, adenosine resulted in similar effects, with no significant differences in the magnitude of the ventilatory response; however, compared with the normoxic state, the intensity of the dyspneic response was significantly (p < 0.05) reduced, whereas the heart rate response increased significantly (p < 0.05). These data indicate that intravenous adenosine-induced dyspnea is not associated with bronchospasm in normal subjects. ...

/SIGNS AND SYMPTOMS/ ... Even when adenosine is ineffective as an agent of chemical cardioversion, it may slow the cardiac rate to allow an analysis of the underlying rhythm. Common adverse effects include facial flushing, shortness of breath, and chest pain. Major contraindications include heart blocks and known adenosine hypersensitivity.

/SIGNS AND SYMPTOMS/ Human systemic effects by intravenous route: coma, convulsions, cyanosis, fall in BP, pulse rate decrease, pulse rate increase.

For more Human Toxicity Excerpts (Complete) data for Adenosine (17 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Adenosine

vNo-DILI-concern

0

No match

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Acute Exposure/ ... Cultured retinal neurons obtained from fetal Wistar rats (gestational age 18-19 days) were maintained for 10-11 days. Neurons were exposed to NMDA (1.0 mM) for 10 min with or without adenosine or to NMDA with adenosine receptor agonists or antagonists. Neuronal death was assessed by the trypan-blue exclusion method 24 hr after the exposure. RESULTS: Adenosine at doses of 0.01 microM and higher significantly protected (p < 0.05, Dunnett) primary cultured fetal rat retinal neurons from apoptotic and/or necrotic death induced by NMDA (1.0 mM). The protective effect of adenosine (10 microM) against NMDA-induced neuronal death was lost by simultaneous exposure to selective A1 receptor antagonist but not to A2a receptor antagonist. Selective A1 receptor agonists had similar effects as adenosine, but A2a receptor agonists and 8-Br-cyclic AMP had no effect on cell viability.

/GENOTOXICITY/ 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.

/GENOTOXICITY/ Adenosine was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.

/OTHER TOXICITY INFORMATION/ Priapism is defined as abnormal prolonged penile erection lasting at least for 4 hours occurring without sexual interest. Forty percent of sickle cell disease (SCD) patients display priapism. The disorder is dangerous and urgent given its association with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. Current strategies to manage the disorder are poor due to lack of fundamental understanding of the molecular mechanisms of priapism. Adenosine is a signaling nucleoside that elicits many pathophysiological effects by engaging membrane receptors. Recent evidence shows that adenosine may play an important role in priapism via adenosine receptor. ...To summarize the recent findings on the importance of adenosine signaling in the pathogenesis of priapism. ... Evidence in the literature on the association between adenosine signaling and the development of priapism. ... This article reviews the literature that relates to the contributory role of adenosine signaling in priapism in multiple animal models and humans. ... Excessive adenosine accumulation in the penis, coupled with increased A(2B)R signaling, contributes to priapism in two independent lines of mutant mice. One is adenosine deaminase (ADA)-deficient mice, the only animal displaying spontaneously prolonged penile erection, and the other is SCD transgenic mice, a well-accepted priapic animal model. Both polyethylene glycol-modified ADA (PEG-ADA) enzyme therapy and A(2B)R antagonists are capable of inhibiting potent corpus cavernosal vascular relaxation associated with priapic-like activity seen in both ADA-deficient mice and SCD transgenic mice, indicating that PEG-ADA enzyme therapy is likely to be a novel therapy for such a dangerous urological disorder. ... Overall, the research reviewed here raises the intriguing possibility that elevated adenosine signaling contributes to priapism in general and that this signaling pathway represents a potentially important therapeutic target for the treatment of priapism.

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.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl adenosine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Residues of adenosine are exempted from the requirement of a tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredients in pesticide formulations applied to growing crops only. Use: Synergist. Limit: Maximum of 0.5% of formulation.

C01EB10

C - Cardiovascular system

QC - Cardiovascular system

Adenosine is indicated as an adjunct to thallium-201 in myocardial perfusion scintigraphy and also indicated for conversion of sinus rhythm of paroxysmal supraventricular tachycardia. Adenosine has a short duration of action as the half life is <10 seconds, and a wide therapeutic window. Patients should be counselled regarding the risk of cardiovascular side effects, bronchoconstriction, seizures, and hypersensitivity.

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.

Adenosine is an endogenous nucleoside present in all cells of the body. Adenosine may exert its pharmacologic effects by activation of purine (cell-surface A1 and A2 adenosine) receptors; relaxation of vascular smooth muscle may be mediated by reduction in calcium uptake through inhibition of slow inward calcium current and activation of adenylate cyclase in smooth muscle cells. Adenosine may reduce vascular tone by modulation of sympathetic neurotransmission.

Adenosine has negative chronotropic, dromotropic, and inotropic effects on the heart. The drug slows conduction time through the AV node and can interrupt AV nodal reentry pathways, leading to restoration of normal sinus rhythm in patients with PSVT, including that associated with Wolff-Parkinson-White syndrome.

Adenosine is a potent vasodilator in most vascular beds, except in renal afferent arterioles and hepatic veins where it produces vasoconstriction. Adenosine is thought to exert its pharmacological effects through activation of purine receptors (cell-surface A1 and A2 adenosine receptors). Although the exact mechanism by which adenosine receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A2 receptors in smooth muscle cells. Adenosine may also lessen vascular tone by modulating sympathetic neurotransmission. The intracellular uptake of adenosine is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, adenosine is rapidly phosphorylated by adenosine kinase to adenosine monophosphate, or deaminated by adenosine deaminase to inosine. These intracellular metabolites of adenosine are not vasoactive. Myocardial uptake of thallium-201 is directly proportional to coronary blood flow. Since Adenoscan significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, Adenoscan causes relatively less thallium-201 uptake in vascular territories supplied by stenotic coronary arteries ie, a greater difference is seen after Adenoscan between areas served by normal and areas served by stenotic vessels than is seen prior to Adenoscan.

... Current evidence suggests that ADO-metabolizing enzymes such as ecto-5'-nucleotidase or ADO deaminase, as well as enzymes that degrade ATP to adenosine, play an important role in the vasoconstrictor signals sent from the macula densa to the afferent arterioles when tubuloglomerular feedback is activated; increased ADO concentration induced by temporal infusion of AngII results in downregulation of A2 ADO receptors, leading to a predominant effect of A1 receptors; the alteration in the ADO receptors balance further contributes to the synergic interaction between ADO and AngII. ... The ADO-metabolizing enzymes have become important regulators of the effects of ADO on the tone of the afferent and efferent arterioles. As AngII is able to increase de-novo renal ADO content through decrease of ADO-metabolizing enzymes, accumulation of ADO induces downregulation of ADO A2 receptor population without modifying ADO A1 receptor, thereby enhancing the constrictive effects of AngII in the renal vasculature.

For more Mechanism of Action (Complete) data for Adenosine (7 total), please visit the HSDB record page.

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

... The plasma half-life of adenosine is less than 10 seconds.

Adenosine can be phosphorylated by adenosine kinase to form adenosine monophosphate. From there, it is phosphorylated again by adenylate kinase 1 to form adenosine diphosphate, and again by nucleoside diphosphate kinase A or B to form adenosine triphosphate. Alternatively, adenosine can be deaminated by adenosine deaminase to form inosine. Iosine is phosphorylated by purine nucleoside phosphorylase to form hypoxanthine. Hypoxanthine undergoes oxidation by xanthine dehydrogenase twice to form the metabolites xanthine, followed by uric acid.

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.

Adenosine is rapidly metabolized intracellularly to the inactive metabolites adenosine monophosphate and inosine ... The drug is cleared by cellular uptake, principally by erythrocytes and vascular endothelial cells, via a specific transmembrane nucleoside transport system.

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, ... excessive amounts may be deaminated by an ecto-form of adenosine deaminase.

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. Half Life: Less than 10 secs

K72T3FS567

ADENOSINE

Established Pharmacologic Class [EPC] - Adenosine Receptor Agonist

Mechanisms of Action [MoA] - Adenosine Receptor Agonists

Adenosine is an Adenosine Receptor Agonist. The mechanism of action of adenosine is as an Adenosine Receptor Agonist.

ADENOSINE

Compounds capable of relieving pain without the loss of CONSCIOUSNESS.

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.

Drugs used to cause dilation of the blood vessels.

Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.

Data regarding the absorption of adenosine are not readily available.

Adenosine is predominantly eliminated in the urine as uric acid.

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

Data regarding the clearance of adenosine are not readily available.

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.

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.

CIR ingredient: Adenosine

... conversion to siuns rhythm of paroxysmal supraventricular tachycardia (PSVT)

Potent vasodilator ... indicated as an adjunct to thallium-201 mycocardial perfusion scintigraphy in patients unable to exercise adequately

Biochemical research.

Therapeutic Category: Antiarrhythmic

Use (kg) in USA (2002): 38

Adenine

Adenosine 3'-(dihydrogen phosphate)

Adenosine 3'-(tetrahydrogen triphosphate)

Adenosine 3'-(trihydrogen diphosphate)

D-ribose

Boniton

Myocol

Nucleocardyl

Sandesin