Caffeine

Caffeine
ATC Code D11AX26, N06BC01
Formula C8H10N4O2
Molar Mass (g·mol−1) 194,19
Physical State solid
Density (g·cm−3) 1,23
Melting Point (°C) 236
PKS Value 14
CAS Number 58-08-2
PUB Number 2519
Drugbank ID DB00201
Solubility wenig löslich in Wasser

Basics

Caffeine is a substance found naturally in many stimulants such as coffee and tea, and as an additive in products such as energy drinks and pharmaceuticals. Caffeine stimulates alertness and concentration and is the most widely consumed psychoactive substance in the world.

Applications and indications

Caffeine is used in medicine for several purposes.

  • In tablet form and as a monopreparation, it can be used to suppress symptoms of fatigue for short periods of time. In this form, it is available without a doctor's prescription as an "over-the-counter" product.
  • Caffeine in combination with certain painkillers, such as paracetamol or acetylsalicylic acid, can increase the analgesic effect by a factor of about 1.5.
  • Caffeine in the form of the salt caffeine citrate can be used as an infusion solution to treat respiratory arrest in newborns. In addition, it is used in this form to prevent bronchopulmonary dysplasia, which occurs mainly in premature infants.

History

In its natural form as an ingredient in tea leaves and coffee beans, caffeine has been used for thousands of years for its stimulating and stimulating effects. As early as 3000 BC, black tea leaves were reportedly used in China to prepare stimulating drinks. Other plants, such as the coffee bean or the kola nut, have also been processed and consumed for their effects in various cultures.

Caffeine in its pure form was first isolated from coffee beans in 1820 by German pharmacist Friedlieb Ferdinand Runge. About 15 years later, the sum formula of the substance was determined. The complete elucidation of the chemical structure and the complete synthesis was achieved by the German chemist Emil Fischer at the end of the 19th century.

Originally, it was thought that the caffeine found in black tea, formerly called tein, was a completely different substance, since the effects of coffee and tea are slightly different. This is due to the fact that the caffeine in black tea is bound to certain substances (polyphenols), which delays its release and makes the effect last much longer than after drinking coffee.

Caffeine was first used medicinally in the early 20th century, when it was discovered that caffeine has a mild bronchodilator effect, which is why it was used in the treatment of asthma.

Pharmacology

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.

Respiration

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.

Renal System

Caffeine has a diuretic effect due to its stimulating effect on renal blood flow, increasing glomerular filtration, and increasing sodium excretion.

Cardiovascular system

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.

Pharmacokinetics

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.

Drug Interactions

Interactions may occur with the following substances:

  • Quinolones e.g., ciprofloxacin.
  • Theophylline
  • Duloxetine
  • preparations of ephedra herb or guarana
  • Rasagiline
  • Tizanidine

Toxicity

Contraindications

Patients with cardiac arrhythmias should avoid especially high doses of caffeine. Patients with gastrointestinal ulcers should not take caffeine. Administration to children is also not recommended.

Side effects

  • Gastrointestinal problems
  • Heartburn
  • nervousness
  • restlessness
  • irritability
  • high blood pressure
  • irregular heart rhythm
  • nausea
  • zanh discoloration

Dependence

Regular consumption can lead to dependence and tolerance symptoms. With abrupt discontinuation, withdrawal symptoms such as caffeine withdrawal headache and irritability may occur.

Pregnancy and lactation

The World Health Organization recommends that pregnant women should not exceed 200-300 mg of caffeine per day. Recent studies suggest that even this dose may already be too high for some women. A lower dose or avoidance of caffeine is therefore recommended.

Sources

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