Review uncovers synergistic molecular toxicity and metabolic saturation during caffeine overdose, indicating the need for hemodialysis in severe cases.
Key Points
To provide a comprehensive clinical and toxicological framework detailing the molecular mechanisms, toxicokinetics, and clinical outcomes of acute caffeine poisoning.
Conducted a comprehensive literature search across PubMed, Scopus, and Google Scholar utilizing AI-assisted search tools.
Prioritized clinical, forensic, toxicokinetic, and molecular mechanism studies, while excluding investigations focused on chronic moderate intake.
Fatalities occur with ingestions of 3–10 g, and serious clinical toxicity emerges at plasma concentrations ≥15 mg/L through progressive adenosine receptor antagonism, phosphodiesterase inhibition, calcium release, and GABA-A antagonism.
Overdose saturates the CYP1A2 metabolic pathway, prolonging elimination half-life up to 27 hours, with concurrent inhibitors like mexiletine sharply diminishing clearance.
Toxicity triggers severe neurological, cardiovascular, and metabolic complications, identifying hypokalemia as an actionable biomarker of poisoning severity.