Pharmacodynamics and mechanism of action
Caffeine has a very wide range of effects, not all of which are medical. Caffeine stimulates the central nervous system (CNS), increasing alertness and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates contraction of the heart muscle, and to a lesser extent improves athletic performance. Caffeine stimulates gastric acid secretion and increases gastrointestinal motility. It also has a mild diuretic effect.
The exact mechanism of action of caffeine is extremely complex because it affects multiple body systems.
General effects at the cellular level
Caffeine exerts its effects on cells through several mechanisms, not all of which are fully understood. One important mechanism that partially explains the stimulatory effects of caffeine is the competitive inhibition of adenosine receptors. Adenosine is a messenger substance in nerve cells and a breakdown product of the cells' energy metabolism. When a large amount of energy is expended, the concentration of adenosine in the cells increases, which then binds to its receptor and signals the cell to expend less energy. This generally leads to fatigue and ensures that we get enough sleep. During sleep, adenosine can be broken down and the energy supply to the cells restored. Caffeine, due to its structural similarity to adenosine, has the ability to occupy the same receptor without activating it. This results in the suppression of fatigue.
Another important mechanism is the inhibition of a specific phosphodiesterase that catalyzes the breakdown of cyclic adenosine monophosphate (cAMP). cAMP is an important second messenger involved in many cellular processes. It activates the enzyme protein kinase A, which plays an important role in the release of glucose from the liver and the supply of energy to muscle cells. In addition, cAMP causes storage fat to become available by activating certain lipases. Caffeine inhibits phosphodiesterase, which increases the level of cAMP in cells and enhances the aforementioned effects of the neurotransmitter.
The exact mechanism of action of caffeine in the treatment of apnea associated with premature infants is not known, but several mechanisms have been considered. The most likely explanation is that by blocking adenosine receptors, respiratory drive is increased by a response of the brain medulla to carbon dioxide, and caffeine simultaneously causes increased contractility of the diaphragm.
Central nervous system
Caffeine exhibits antagonism of all 4 adenosine receptor subtypes in the central nervous system. The effects of caffeine on alertness and combating drowsiness are specifically associated with antagonism of the A2a receptor.
Caffeine has a diuretic effect due to its stimulating effect on renal blood flow, increasing glomerular filtration, and increasing sodium excretion.
Adenosine receptor antagonism at the A1 receptor by caffeine stimulates contractile (inotropic) effects in the heart. Blockade of adenosine receptors promotes the release of catecholamines, resulting in stimulatory effects in the heart and the rest of the body. In the blood vessels, caffeine exerts direct antagonism on adenosine receptors, causing vasodilation. It stimulates endothelial cells in the blood vessel wall to release nitric oxide, which increases blood vessel relaxation. However, the release of catecholamine counteracts this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. The vasoconstrictive effects of caffeine are beneficial for migraine and other types of headaches, which are usually caused by vasodilation in the brain.
Caffeine is rapidly absorbed after oral or parenteral administration, reaching maximum plasma concentrations within 30 minutes to 2 hours. After oral administration, the effect occurs within approximately 45 minutes. Food may delay the absorption of caffeine. Absolute bioavailability reaches nearly 100% in adults. Caffeine has the ability to rapidly cross the blood-brain barrier, which is why it can exert its wakefulness-inducing effects. It is water and fat soluble and is distributed throughout the body. The protein binding of the substance is about 10-36%. The metabolism of caffeine occurs mainly in the liver via the enzyme cytochrome CYP1A2. Products of caffeine metabolism include paraxanthine, theobromine, and theophylline. These metabolites are excreted mainly in the urine. In an average-sized adult, the half-life is approximately 5 hours, but may differ by more than 50% in smokers.
Interactions may occur with the following substances:
- Quinolones e.g., ciprofloxacin.
- preparations of ephedra herb or guarana