Adenosine: What is it? Uses, Dosage, Interactions, Side Effects and Precautions

ATP is the main source of energy in cells for transport systems and many enzymes.

Adenosine is a naturally occurring purine nucleoside that is formed from the breakdown of adenosine triphosphate (ATP).

The majority of ATP is hydrolyzed to ADP, which can be further dephosphorylated to AMP.

Most ADP and AMP that are 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 (ie, 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 a number of different physiological actions.

An important action is the relaxation of vascular smooth muscle, which leads to vasodilation.

This is a particularly important 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 relaxation of smooth muscle by inhibiting the myosin light chain kinase, which leads to a decrease in myosin phosphorylation and a decrease in contractile force.

There is also evidence that adenosine inhibits the entry of calcium 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, as well as the opening of potassium channels.

In cardiac tissue, adenosine binds to type 1 receptors (A1), which are coupled to 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 entry of calcium 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 located 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 atrioventricular block.

Keep in mind, however, 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 important metabolic targets for adenosine.

More importantly, adenosine is rapidly transported to red blood cells (and other cell types) where 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, which reduces the metabolism of adenosine.

Therefore, an important mechanism for vasodilatation induced by dipyridamole is its enhancement of extracellular adenosine.

Adenosine kinase can act on adenosine and re-phosphorylate 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 be effective in treating herpes zoster ( shingles ) infection and in preventing the nerve pain that follows these infections.
  • Lung cancer: studies in development suggest that ATP is not effective 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, 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 unspecified 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 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 can reduce the effectiveness of gout medications.
  • Methylxanthines: Methylxanthines can block the effects of adenosine. Adenosine is often used by doctors 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
  • Difficult or difficult breathing.
  • Stunning or dizziness
  • Discomfort in the throat, neck or jaw.
  • Chest tightness.
  • Diarrhea.
  • 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, strong or accelerated heartbeats.
  • Headache.
  • Nervousness.
  • Knocking in the ears.
  • Area of ​​decreased vision
  • Tos.
  • 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 with caution if the benefits outweigh the risks).

Studies in animals show risk studies and in humans not available or studies were not conducted in animals or humans.

High potential for serious adverse reactions in infants; the importance of the medication for the mother should be taken into account when making the decision 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 for the treatment of PSVT in neonates, infants, children and adolescents.

Geriatric use

In general, Adenosine in geriatric patients should be used with caution since this population may have decreased cardiac function, nodal dysfunction, concomitant diseases or pharmacotherapy that may alter hemodynamic function and produce severe bradycardia or AV block.