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Pharmacokinetics of Caffeine

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Caffeine is a naturally occurring alkaloid found in more than 60 plants 23. Methylxanthine caffeine is one of the most widely consumed stimulants in the world. It is a mild central nervous system stimulant, a vasodilator, and a diuretic 22. Caffeine is present in wide range of dietary products such as coffee, tea, coca, candy bars, soft drinks and energy drinks. In addition, a number of prescription and over-the-counter drugs (OTCs), which are used for headache, cold, allergy, and pain relief and alerting drugs, are often combined with caffeine. Some examples of these drugs are as follows: No-Doz, No-Doz Plus and Cafergot 24, 25.

After oral ingestion, caffeine is rapidly and almost completely absorbed from the gastrointestinal tract and reaches peak plasma concentrations in about 30-60 mins after consumption. The volume of distribution is 0.6L/Kg and 36% is protein bound. It passes through the blood brain barrier and all biological membranes. It is metabolized in the liver by the cytochrome P450 (CYP) system to dimethylxanthine stimulants theobromine and theophylline. The elimination half-life is 4.5 hours in healthy nonsmoking adults.

Mechanism of Action

Adenosine A1 and A2A receptors are present in the basal ganglia. Basal ganglia are a group of structures which help in various motor controls. As shown in Table 1, adenosine A1 receptors are present in all brain areas whereas A2A receptors are found more in the dopamine rich regions of the brain. There is evidence that A2A receptors interact with the dopamine system, which is involved in reward and arousal effects 27.

Caffeine acts as an antagonist to both types of the receptors. The overall psychostimulant properties of caffeine in brain are mediated by its ability to interact with neurotransmission in different regions of the brain. It has been indicated that caffeine particularly affects a group of projection neurons located in the striatum, which is the main receiving area of the basal ganglia 29. Thus, caffeine blocks the inhibitory neurotransmitter adenosine, inhibits phosphodiesterase and increases intracellular cyclic adenosine monophosphate (cAMP) 28. At low concentration, it blocks adenosine receptors however, at higher concentration, it is found to inhibit phosphodiesterase and calcium mobilization 27.Physiological effects

In a literature review by Glade, caffeine at moderate amounts was found to increase energy, decrease fatigue, enhance physical, motor and cognitive performances, increase alertness, decrease mental fatigue, increase the accuracy of reaction and enhance cognitive functioning capabilities and neuromuscular coordination 30. The author did not specify the effective dose in the study. However, the medical website Rx-list has mentioned that doses of 100-200 mg caffeine can increase alertness, relieve drowsiness and improve thinking and at doses of 250-700 mg/day, caffeine can cause anxiety, insomnia, nervousness, hypertension, and insomnia 31. Moreover, an article by Pohler mentions that caffeine can affect all the organ systems in the body if taken in excess amounts (Table 2) 32.

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Pharmacokinetics of Caffeine. (2019, February 11). GradesFixer. Retrieved December 7, 2022, from
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