Amiodarone Vs Adenosine Vs Atropine: Uses, Mechanisms, and Side Effects

In this article, we will take a close look at three important medications in the treatment of arrhythmias: amiodarone, adenosine, and atropine. We will understand their uses in the medical field, particularly in managing heart rhythm disorders, cardiovascular conditions, and muscle spasms. We will also explore their mechanisms of action and potential side effects, providing a comprehensive understanding of these drugs.
Jakub Gwiazdecki

Jakub Gwiazdecki

Fifth year medical student at the Medical Faculty of Comenius University in Bratislava.

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What is Amiodarone?

Amiodarone is a drug used in the treatment of various heart rhythm disorders. It belongs to the class III antiarrhythmic drugs prescribed, especially in ventricular and supraventricular arrhythmias [1, 2]. It is known to be very effective in the treatment of atrial fibrillation [3]. As this medication is an iodinated benzofuran derivative, it contains up to 40% iodine [4].

Amiodarone reduces the sympathetic effect of the autonomic nervous system on the heart. It is also known for its ability to prolong the refractory period in the heart cells. The refractory period is a time during which heart signals cannot excite the heart cells [1].

It interacts with other medications, among which are digoxin, warfarin, and class I antiarrhythmic drugs [1].

Indication for Amiodarone

Indications for amiodarone include:

Mechanism of action of Amiodarone

Amiodarone works by inhibiting various types of myocardial potassium channels. The blockage of these channels results in longer refractory periods and, thus, longer breaks between the heartbeats [6].

Thanks to the inhibition and longer resting, non-excitable time, amiodarone limits the spread of unwanted additional electric stimuli, which leads to fibrillation or arrhythmias. The rhythm becomes slower and more regular.

Side effects of Amiodarone

Amiodarone is effective in rhythm stabilization and arrhythmia prevention, but it has its side effects. The most popular side effects are:

  • nausea
  • constipation
  • vomiting
  • fatigue
  • coordination problems
  • sleep disturbance
  • headache
  • stomach pain [7].

The more serious side effects include allergic reactions. They can take various forms, ranging from rashes to hives and swellings of the face and lips. Also, respiratory problems can occur. A side effect can be difficulty breathing, coughing, chest pain, or shortness of breath. Amiodaron can also change the vision. It can lead to higher light sensitivity and blurred sight [7].

Some other problems amiodarone can cause are hepatic side effects. They can exhibit tiredness and weakness with changes in the skin color and darkening of the urine.

Even though it is an antiarrhythmic drug, it can also cause chest pain with an irregular heartbeat, and fainting can also occur [7].

Other serious side effects are damage to the nerves and numbness in the extremities [7].

In rare cases, amiodarone can cause acute pancreatitis [8], liver cirrhosis [9], and alveolar hemorrhage [10].

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What is Adenosine?

Adenosine is a body-produced and found nucleoside. It is found in all cells of the body and plays a key role in many biochemical reactions. The levels of adenosine can increase in oxygen-demand situations like trauma, hypoxia, and metabolic stress [11, 12, 13].

In the body, adenosine is formed from adenosine-triphosphate (ATP) during energy-consuming processes, when this molecule loses all three phosphate groups [14].

In the vasculature, adenosine serves as a vasodilator and contributes to vessel remodeling and inflammatory reactions. In wounds and tumors, it serves as an angiogenesis stimulator, leading to the creation of new vessels [11].

Indication for Adenosine

Adenosine is indicated in:

  • diagnosis and treatment of supraventricular tachycardia
  • atrioventricular nodal reentry tachycardia [15]
  • Wolff-Parkinson-White syndrome [15]
  • paroxysmal tachycardia [16].

Mechanism of action of Adenosine

Adenosine works through G-protein-coupled receptors. Once activated, they promote many intracellular pathways. There are four known types of adenosine receptors: A1, A2A, A2B, and A3 [17, 18].

Adenosine's mechanism of action on the heart is not fully understood. However, it exerts cardioprotective properties, especially in stressful events. During ischemia (lack of oxygen) in the heart, it is released in large amounts. Its action on the myocardial cells leads to slower action in the heart, which lowers the oxygen demand [19].

Side effects of Adenosine

The most common side effects of adenosine include:

  • difficulty breathing [20],
  • warm flushes [20]
  • chest pain [21]
  • headache [20]
  • nausea [22]

In some cases, adenosine can lead to more serious side effects. For instance, it can cause bronchospasm, making breathing very difficult for the affected [22].

Adenosine can also cause heart side effects. One in ten can experience a first-degree atrioventricular block, and in some cases, second- or third-degree AV blocks can also occur [21]. In rare cases, adenosine administration can cause ventricular arrhythmias [23].

What is Atropine?

Atropine is an anticholinergic drug that blocks the action of acetylcholine. The inhibition of the action of this neurotransmitter can relieve, for example, muscle cramps. From a chemical point of view, atropine is a tropane alkaloid with potent bioactive properties. It can be extracted from the seeds of the Datura plant, which is native to North America [24, 25].

In medicine, atropine is mostly used in cardiology and ophthalmology, but also in surgery for gland secretion control [26]. In the heart, it helps to increase the heartbeat. In ophthalmology, atropine is used in the treatment of conditions like mydriasis, cycloplegia, and amblyopia [27]. After or during an operation, a few drops of this anticholinergic drug can reduce salivation and bronchial secretions, making the surgery easier to perform [26].

Indication for Atropine

In clinical applications, atropine is indicated in many situations, among the most important are:

  • asymptomatic and symptomatic bradycardia [28]
  • mouth and respiratory surgeries [28]
  • poising with carbamate or organophosphate insecticides, nerve agents, and muscarine-containing mushrooms [28]
  • mydriasis, amblyopia, and cycloplegia [28]
  • chronic sialorrhea [28]
  • heart stress test in poor heart response and exercise capacity [29]

Mechanism of action of Atropine

The main mechanism by which atropine works is by blocking the calming part of the autonomic nervous system. The inhibition allows the heart to increase its rate and beat faster. This normally leads to tachycardia, a heartbeat above 100 beats per minute [30].

Another effect atropine has is the inhibition of phosphodiesterase type 4, an intracellular pathway receptor. This also leads to an increase in heart rate as well as an increase in contractility [30]. The effect on internal heart cell modulation potentiates the effect of the neuronal modulation of the autonomic nervous system. Additionally, it shows the potent arrhythmogenic effect this drug can have on the heart [30].

In addition to its effects on the heart, atropine also induces the peripheral vessels, leading to their dilation. The increased perimeter of the blood-transporting tubes is achieved by increased calcium release from the smooth muscles of the peripheral arteries. Lower internal levels of calcium in those muscles lead to relaxation and dilation [31].

Side effects of Atropine

Atropine can cause a range of side effects. They vary in severity and depend on the way atropine is administered. In cardiological use, the side effects include:

  • fever,
  • fast heartbeat
  • arrythmia
  • urination difficulties [32].

Topical administration on the eyes can cause:

  • irritation and redness,
  • light sensitivity,
  • swelling of the eyelids,
  • dry mouth,
  • blurred vision [32].

However, patients receiving ophthalmic atropine can also suffer from dysrhythmias like atrial fibrillation and supraventricular tachycardia [33].

In children, especially common are fever and flushed faces [34]. In some patients with asthma, atropine can cause prolonged gastric emptying [35].

In rare cases, atropine can cause poisoning. Toxic effects of this condition include high fever, flushing, racing heartbeat, dry mouth, dry skin, and difficulty urinating [36].

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Jakub Gwiazdecki

Jakub Gwiazdecki

Jakub is in his fifth year as a medical student at Comenius University in Bratislava, Slovakia. He has special interested in cardiology and in patient-centered medicine. His love for heart health isn't just book-smarts; he wants to know how it works, what it means for our feelings, and how key it is for health and happiness. Jakub thinks real good health care comes from always putting the patient at the centre, treating each person as a whole.