Index
ATP is the primary energy source in cells for transport systems and many enzymes.
Adenosine is a naturally occurring purine nucleoside formed from the breakdown of adenosine triphosphate (ATP).
Most ATP is hydrolyzed to ADP, which can be further dephosphorylated to AMP.
Most ADP and AMP formed in the cell are rephosphorylated in the mitochondria by enzymatic reactions that require oxygen.
If there are large amounts of hydrolyzed ATP, and especially if there is sufficient oxygen available (i.e., hypoxia ), then part of the AMP can be further dephosphorylated to Adenosine by the cell membrane-associated enzyme, 5′-nucleotidase.
Adenosine can bind to purinergic receptors in different cell types, where it can produce several different physiological actions.
Necessary action is the relaxation of vascular smooth muscle, which leads to vasodilation.
This is a fundamental mechanism for linking coronary blood flow to the metabolic needs of the heart.
In coronary vascular smooth muscle, Adenosine binds to adenosine receptors type 2A (A2A), which are coupled to the Gs protein.
The activation of this G protein stimulates adenylyl cyclase, increases AMP, and causes the activation of the protein kinase.
This stimulates the KATP channels, which hyperpolarizes the smooth muscle, causing relaxation.
Increased cAMP also causes smooth muscle relaxation by inhibiting the myosin light chain kinase, which leads to a decrease in myosin phosphorylation and contractile force.
There is also evidence that Adenosine inhibits calcium entry into the cell through the L-type calcium channels.
Since calcium regulates the contraction of smooth muscle, the reduction of intracellular calcium causes relaxation.
In some types of blood vessels, there is evidence that Adenosine produces vasodilation through increases in GMP, which leads to the inhibition of calcium entry into cells and the opening of potassium channels.
In cardiac tissue, Adenosine binds to the type 1 receptor (A1), coupled with Gi proteins.
Activation of this pathway opens potassium channels, which hyperpolarize the cell.
The activation of the Gi protein also decreases the AMP, which inhibits the L-type calcium channels and, therefore, the calcium entry into the cell.
Inhibition of L-type calcium channels also decreases conduction velocity (negative dromotropic effect), particularly in atrioventricular (AV) nodules.
Finally, Adenosine acting on the presynaptic purinergic receptors in the sympathetic nerve terminals inhibits the release of norepinephrine.
In terms of its electrical effects on the heart, Adenosine decreases the heart rate and reduces the conduction velocity, especially in the AV node, which can produce an atrioventricular block.
However, remember that when Adenosine is infused into humans, the heart rate increases due to baroreceptor reflexes caused by systemic vasodilation and hypotension.
Adenosine has a very short half-life. In human blood, its half-life is less than 10 seconds. There are two critical metabolic targets for Adenosine.
More importantly, Adenosine is rapidly transported to red blood cells (and other cell types). Adenosine deaminase rapidly passes into inosine, which is then broken down into hypoxanthine xanthine and uric acid, which is excreted by the kidneys.
Deamination with Adenosine also occurs in plasma but at a slower rate than what occurs within cells.
Dipyridamole is a vasodilator drug that blocks the absorption of Adenosine by cells, reducing Adenosine metabolism.
Therefore, an essential mechanism for vasodilatation induced by dipyridamole is its enhancement of extracellular Adenosine.
Adenosine kinase can act on Adenosine and rephosphorylate it to AMP. This rescue route helps maintain the set of adenine nucleotides in the cells.
Applications
Effective for:
• The treatment of certain types of irregular heartbeats: as an intravenous medication only by prescription.
Possibly effective for:
- Treat weight loss in people with advanced cancer: intravenous ATP seems to improve appetite, food intake, and quality of life in people with advanced non-small-cell lung cancer and other tumors.
- Wounds: usually in the legs due to poor circulation (venous stasis ulcers). Intramuscular AMP can relieve fluid retention, itching, swelling, and redness due to venous stasis ulcers.
Insufficient evidence of:
- Herpes zoster: early research suggests that AMP administered by muscle injection may effectively treat herpes zoster ( shingles ) infection and prevent the nerve pain that follows these infections.
- Lung cancer: studies in development suggest that ATP is ineffective in treating non-small cell lung cancer.
- Pain.
- Other conditions.
Dosage
Adult in injectable presentation
- 6 mg IVP for 1-3 seconds (can be administered intravenously); if there is no conversion within 1-2 minutes, give 12 mg IVP, and repeat a second time if necessary (30 mg total).
Pediatric in injectable presentation
- 0.05 to 0.1 mg / kg of rapid PIV for 1-3 seconds.
- If necessary, you can administer the second dose of 0.2 mg IVP without exceeding the cumulative dose of 12 mg.
In geriatric patients
The elderly can experience more adverse effects of Adenosine; they may be more sensitive if the cumulative dose of 12 mg is exceeded.
- 6 mg IVP for 1-3 seconds (can be administered intravenously), if there is no conversion within 1-2 minutes, give 12 mg IVP, repeat a second time if necessary (30 mg total).
Interactions
Important interaction
Do not take this combination:
- Dipyridamole (Persantine): the body breaks down Adenosine to get rid of it. Dipyridamole (Persantine) can decrease the decomposition of Adenosine. Decreasing the degradation of Adenosine can cause heart problems. Do not take Adenosine if you are taking dipyridamole (Persantine).
Moderate interaction
Be careful with this combination:
- Carbamazepine (Tegretol): Adenosine can slow the heart rate. Taking carbamazepine (Tegretol) with Adenosine can make the heart beat too slow. Do not take Adenosine if you are taking carbamazepine (Tegretol).
- Difilin: Difilin reduces the effects of Adenosine by pharmacodynamic antagonism.
- Green tea: green tea decreases the effects of Adenosine by an unknown mechanism of interaction.
- Hawthorn: Hawthorn increases the effects of Adenosine by pharmacodynamic synergism.
- Inhaled nicotine: inhaled nicotine increases the effects of Adenosine by an unknown mechanism—tachycardia associated with Adenosine and pain in the chest.
- Intranasal nicotine : intranasal nicotine increases the effects of Adenosine by an unknown mechanism. Tachycardia is associated with Adenosine and pain in the chest.
- Sevelamer: sevelamer decreases adenosine levels by increasing elimination.
Minor interaction
Be careful with this combination:
- Drugs for gout: gout is caused by an accumulation of uric acid crystals in the joints. Adenosine can increase uric acid in the body and reduce gout medications’ effectiveness.
- Methylxanthines: Methylxanthines can block the effects of Adenosine. Doctors often use adenosine to perform a test on the heart. This test is called a cardiac stress test.
Other medications with low interaction are:
- Atenolol.
- Betaxolol.
- Bisoprolol.
- Carvedilol.
- Esmolol.
- Labetalol.
- Lily of the valley.
- Metoprolol.
- Nadolol.
- Nebivolol.
- Penbutolol.
- Pindolol.
- Propranolol.
- Sotalol.
Side effects
Along with its necessary effects, Adenosine can cause some unwanted effects. Although not all of these side effects can occur, if they do occur they may need medical attention.
Some side effects of Adenosine can occur and usually do not require medical attention.
These side effects may go away during treatment as your body adjusts to the medication.
Check with your doctor or nurse right away if you experience any of the following side effects while taking Adenosine:
More common
- Chest discomfort
- Complex or difficult breathing.
- Stunning or dizziness
- Discomfort in the throat, neck, or jaw.
- Chest tightness.
- Diarrhea.
- The sensation of warmth.
- Indigestion.
- Loss of appetite
- Nausea or vomiting
- Gas passage.
- Redness of the face, neck, arms, and occasionally, the upper chest.
- Stomach pain, fullness, or discomfort.
Less common
- Chest pain.
- Confusion.
- Dizziness, fainting, or lightheadedness when suddenly rising from a lying or sitting position.
- Fainting.
- Heartbeat: fast, slow, or irregular.
- Perspiration.
- Difficulty breathing.
- Unusual tiredness or weakness
Rare
- Irregular, firm, or accelerated heartbeats.
- Headache.
- Nervousness.
- Knocking-in the ears.
- Area of decreased vision
- To.
- Discomfort in the back, ears, or tongue.
- Drowsiness.
- Dry mouth.
- Metallic flavor.
- Humor changes.
- Tremors in the legs, arms, hands, or feet.
- Nasal congestion.
- Vaginal pressure
- Urinary urgency
- Frequency not reported
- Intracranial pain
- Convulsions
- Heart failure.
- Myocardial infarction.
- Arrhythmia .
- Hypertension .
- Heart failure.
- Transient increase in heart rate.
Precautions
Pregnancy and lactation
Pregnancy category C (Use caution if the benefits outweigh the risks).
Studies in animals show risk studies and in humans are not available, or studies were not conducted in animals or humans.
High potential for severe adverse reactions in infants; the importance of the medication for the mother should be taken into account when deciding to interrupt breastfeeding after the administration of Adenosine or not.
Carcinogenesis and mutagenesis
No animal studies have been conducted to evaluate the carcinogenic potential of Adenocard (adenosine injection).
Adenosine was negative for the genotoxic potential in the Salmonella assay (Ames test) and the mammalian microsome.
However, it is known that Adenosine, like other nucleosides in millimolar concentrations present during several times of duplication of cells in culture, produces a variety of chromosomal alterations.
Pediatric use
There have been no controlled studies 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 to treat PSVT in neonates, infants, children, and adolescents.
