Adenosine: Effects, Uses & Risks

Adenosine is a building block essential for the energy metabolism of the human body. Therapeutically, adenosine is used in particular to regulate cardiac arrhythmias and to lower blood pressure.

What is adenosine?

Therapeutically, adenosine is used in particular to regulate cardiac arrhythmias as well as to lower blood pressure. Adenosine is an endogenous nucleoside that is indispensable for energy metabolism and is composed of the purine base adenine and β-D-ribose. It is the basic building block of adenosine triphosphate (ATP), an important energy supplier for all tissue cells of the human organism. During all energy-consuming cell processes, ATP is broken down to meet energy requirements and its building block adenosine is released. The concentration of adenosine in the blood rises sharply under physical stress. In addition, adenosine is a component of ribonucleic acids (DNA building block), coenzymes as well as nucleoside antibiotics. Adenosine has a similar molecular structure to caffeine and occupies the same receptors, but without stimulating them. The physiological half-life is extremely short, a few seconds.

Pharmacological effects

Adenosine performs significant functions in the human organism. For example, as an important building block of ATP, it serves to regenerate the main energy store involved in all cellular processes. Adenosine is always released from the nerve cells when the energy supply of the neurons is no longer sufficiently ensured. This is the case, among other things, in ischemia (reduced blood flow). In contrast to neurotransmitters (biochemical messengers), the release is not mediated by exocytosis of storage vesicles, but by transport proteins. The transport proteins subsequently also remove the released adenosine from the extracellular space. In ischemia, there is an increased concentration of adenosine in the intracellular space, which causes transport reversal. If released ATP is degraded by ectoenzymes (enzymes acting outside the cell), the extracellular adenosine concentration also increases. In the nervous system, adenosine occupies the receptors provided for caffeine and the neurotransmitters dopamine, norepinephrine and acetylcholine, thus blocking their action. The more active the nerve cells are, the higher the concentration of ATP and thus adenosine. By occupying the receptors, the function of the nerve cells is slowed down and the nervous system is protected from overexertion. As a result of this neurotransmitter blockade, the blood vessels are dilated. There is a consecutive drop in blood pressure (blood pressure reduction) as well as a slowing of the heart rate. Furthermore, via activation of G-protein-modulated potassium channels (via A1 adenosine receptors), the excitation conduction time in the AV node (atrioventricular node) is prolonged. As the secondary pacemaker of the heart, the AV node is the only connection between the atrium and the ventricle (heart chamber) and regulates the conduction of excitation to the heart chambers. Delayed conduction of excitation ensures coordinated contraction of the ventricle and atrium. Because adenosine concentration increases during physical exertion and oxygen deprivation, increased release is thought to prevent inefficient tachycardia and arrhythmias under stress.

Medical application and use

Adenosine is used primarily as an antiarrhythmic agent for the drug treatment of cardiac arrhythmias. Because of its very short half-life in the blood, adenosine can be administered intravenously as a short infusion to control blood pressure (blood pressure reduction) and cardiac rhythm (3, 6, or 12 mg). In this case, adenosine leads to dilatation of the coronary arteries in addition to dilatation of the peripheral vessels. Adenosine can terminate AV node-dependent tachycardias by blocking AV conduction, which is why it is the first-choice drug for supraventricular tachycardias such as AV node reentry tachycardias. In addition, atrial tachycardias such as paroxysmal tachycardias (seizure-like acceleration of heart rate) can be treated with adenosine. Similarly, adenosine is applied within diagnostics during stress examinations for dilatation of the cardiac vessels (imaging of the heart).

Risks and side effects

Locally increased adenosine concentration in the heart due to ischemia may cause bradycardic arrhythmias (bradycardia).Theophylline, as an antidote, inhibits adenosine action at the corresponding receptor of the heart. In addition, therapeutically applied adenosine can cause short-term asystole (lack of myocardial contraction) due to its negative dromotropic effect (slowing of excitation transmission). In these cases, adenosine administration should be discontinued immediately. Due to the short half-life, the pharmacological effect subsides very rapidly. As a result of the vasodilatory effect, flushing symptoms characterized by a brief reddening of the skin may occur. Furthermore, short-term breathing difficulties, a feeling of pressure in the chest area, headache, dizziness, nausea and a tingling sensation may occur with injected adenosine. The use of adenosine is contraindicated in bronchospasm, COPD, and bronchial asthma.