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      The clinical toxicology of caffeine: A review and case study

      review-article
      *
      Toxicology Reports
      Elsevier
      Caffeine, Case reconstruction, Clinical toxicology, Adenosine antagonism, Energy drinks

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          Abstract

          Caffeine is a widely recognized psychostimulant compound with a long history of consumption by humans. While it has received a significant amount of attention there is still much to be learned with respect to its toxicology in humans, especially in cases of overdose. A review of the history of consumption and the clinical toxicology of caffeine including clinical features, pharmacokinetics, toxicokinetics, a thorough examination of mechanism of action and management/treatment strategies are undertaken. While higher (i.e., several grams) quantities of caffeine are known to cause toxicity and potentially lethality, cases of mainly younger individuals who have experienced severe side effects and death despite consuming doses not otherwise known to cause such harm is troubling and deserves further study. An attempted case reconstruction is performed in an effort to shed light on this issue with a focus on the pharmacokinetics and pharmacodynamics of caffeine.

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          Most cited references166

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          Pharmacology of Adenosine Receptors: The State of the Art.

          Adenosine is a ubiquitous endogenous autacoid whose effects are triggered through the enrollment of four G protein-coupled receptors: A1, A2A, A2B, and A3. Due to the rapid generation of adenosine from cellular metabolism, and the widespread distribution of its receptor subtypes in almost all organs and tissues, this nucleoside induces a multitude of physiopathological effects, regulating central nervous, cardiovascular, peripheral, and immune systems. It is becoming clear that the expression patterns of adenosine receptors vary among cell types, lending weight to the idea that they may be both markers of pathologies and useful targets for novel drugs. This review offers an overview of current knowledge on adenosine receptors, including their characteristic structural features, molecular interactions and cellular functions, as well as their essential roles in pain, cancer, and neurodegenerative, inflammatory, and autoimmune diseases. Finally, we highlight the latest findings on molecules capable of targeting adenosine receptors and report which stage of drug development they have reached.
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            Effects of caffeine on human behavior.

            A. Smith (2002)
            The literature suggests that the following effects on behavior of adult humans may occur when individuals consume moderate amounts of caffeine. (1) Caffeine increases alertness and reduces fatigue. This may be especially important in low arousal situations (e.g. working at night). (2) Caffeine improves performance on vigilance tasks and simple tasks that require sustained response. Again, these effects are often clearest when alertness is reduced, although there is evidence that benefits may still occur when the person is unimpaired. (3) Effects on more complex tasks are difficult to assess and probably involve interactions between the caffeine and other variables which increase alertness (e.g. personality and time of day). (4) In contrast to the effects of caffeine consumption, withdrawal of caffeine has few effects on performance. There is often an increase in negative mood following withdrawal of caffeine, but such effects may largely reflect the expectancies of the volunteers and the failure to conduct "blind" studies. (5) Regular caffeine usage appears to be beneficial, with higher users having better mental functioning. (6) Most people are very good at controlling their caffeine consumption to maximise the above positive effects. For example, the pattern of consumption over the day shows that caffeine is often consumed to increase alertness. Indeed, many people do not consume much caffeine later in the day since it is important not to be alert when one goes to sleep. In contrast to effects found from normal caffeine intake, there are reports that have demonstrated negative effects when very large amounts are given or sensitive groups (e.g. patients with anxiety disorders) were studied. In this context caffeine has been shown to increase anxiety and impair sleep. There is also some evidence that fine motor control may be impaired as a function of the increase in anxiety. Overall, the global picture that emerges depends on whether one focuses on effects that are likely to be present when caffeine is consumed in moderation by the majority of the population or on the effects found in extreme conditions. The evidence clearly shows that levels of caffeine consumed by most people have largely positive effects on behavior. Excessive consumption can lead to problems, especially in sensitive individuals.
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              G protein coupled receptor structure and activation.

              G protein coupled receptors (GPCRs) are remarkably versatile signaling molecules. The members of this large family of membrane proteins are activated by a spectrum of structurally diverse ligands, and have been shown to modulate the activity of different signaling pathways in a ligand specific manner. In this manuscript I will review what is known about the structure and mechanism of activation of GPCRs focusing primarily on two model systems, rhodopsin and the beta(2) adrenoceptor.
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                Author and article information

                Contributors
                Journal
                Toxicol Rep
                Toxicol Rep
                Toxicology Reports
                Elsevier
                2214-7500
                03 November 2018
                2018
                03 November 2018
                : 5
                : 1140-1152
                Affiliations
                [0005]EuSci LLC, Gretna, NE, USA
                Author notes
                [* ]Correspondence to: EuSci LLC, 1309 S 204 th St, #293, Elkhorn, NE, 68022, USA. cmwillson@ 123456gmail.com
                Article
                S2214-7500(18)30327-5
                10.1016/j.toxrep.2018.11.002
                6247400
                30505695
                200b255f-fc3d-4938-9b81-1c726ea97880
                © 2018 The Author

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 28 April 2018
                : 9 October 2018
                : 1 November 2018
                Categories
                Article

                caffeine,case reconstruction,clinical toxicology,adenosine antagonism,energy drinks

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