Overdose caffeine

Forman, J., Aizer, A. and Young, C. Myocardial infarction resulting from caffeine overdose in an anorectic woman, Ann Emerg Med 29(1), 178-180, 1997. 

In this section, caffeine is discussed only briefly and the focus is on other stimulants that produce psychiatric disorders. Caffeine can lead to a withdrawal syndrome characterized by lethargy, irritability, and headache, but withdrawal appears to occur in less than 3% of regular coffee drinkers. Moreover, the morbidity associated with caffeine overdose, which can include disturbing effects on sleep and heart rhythm, is much less than the morbidity associated with other stimulants. 

Confirmed reports of caffeine overdose are rare. Postmortem concentrations of caffeine measured in femoral blood were 220 and 190 mg/1 in two adults who took unknown doses (40). In view of the extensive use of caffeine, the authors emphasized the forensic importance of measuring caffeine. 

Anderson BJ, Gunn TR, Hohord NH, Johnson R. Caffeine overdose in a premature infant clinical course and pharmacokinetics. Anaesth Intensive Care 1999 27(3) 307-ll. 

Caffeine is rapidly absorbed after an oral dose, with peak levels reached within 1-2 h at therapeutic doses. Onset of clinical effects occurs within 60 min. In adults, caffeine is extensively metabolized by the liver primarily by N-demethylation. It is excreted in the urine primarily as 1-methyluric acid and 1-methylxan-thine. Theophylline (1,3-dimethylxanthine) is a minor product of caffeine metabolism in adults (< 1%). After massive caffeine overdoses, serum levels of theophylline are measurable. The elimination half-life of caffeine is 3-6 h at therapeutic doses. The half-life is shorter in smokers and is prolonged by oral contraceptives, cimetidine, late pregnancy, and in overdose. The half-life of caffeine is much longer in infants and does not approximate that seen in adults until 6 months of age. The half-life of caffeine may exceed 100 h in preterm infants. Only 1-10% of caffeine appears unchanged in the urine in adults. Neonates may excrete up to 85% of caffeine unchanged. 

Caffeine can have profound effects on the cardiovascular system. At least four mechanisms have been proposed for the pro-arrhythmic potential of caffeine in overdose. First, caffeine increases circulating catecholamines. Second, caffeine inhibits phosphodiesterase. Increased circulating catecholamines after caffeine overdose increase jSl-receptor stimulation. Stimulation of jSl-receptors increases intracellular cAMP by G protein stimulation of adenylate cyclase. The activity of cAMP is prolonged due to its decreased metabolism as phosphodiesterase is inhibited by caffeine. Subsequently, jSl-receptor effects are exaggerated and tachydysrhythmias are induced. Third, caffeine increases myocardial intracellular calcium. Caffeine both induces release of calcium... 

Holstege CP and Hunter Y (2003) Massive caffeine overdose requiring vasopression infusion and hemodialysis. Journal of Toxicology Clinical Toxicology 41 1003-1007. 

Leson CL, McGuigan MA, and Bryson SM (1988) Caffeine overdose in an adolescent male. Clinical Toxicology 26 407-415. 

However, with chronic intoxication, severe toxicity may occur with levels of 40-60 mg/L. Note Acute caffeine overdose (see p 142) will cause a similar clinical picture and will produce falsely elevated theophylline concentrations with most commerci immunoassays. 

B. Reversal of hypotension and tachycardia caused by excessive beta-adrenergic activity resulting from theophylline or caffeine overdose. 

Drug overdose Hemodynamic instabOity and hypotension after massive caffeine overdose improved with loading doses followed by continuous infusions of both phenylephrine and lidocaine [93" ]. Hypotension in caffeine overdose is multifactorial P2-adrenoceptor agonism causes peripheral vasodilatation and Pj-adrenoceptor stimulation leads to profound tachycardia with incomplete diastolic fiUing. The authors suggested that both phenylephrine and lidocaine should be considered in the treatment of cardiovascular collapse secondary to methylxanthine poisoning. 

Kapur R, Smith MD. Treatment of cardiovascular collapse from caffeine overdose with lidocaine, phenylephrine and... 

Physical effects of high doses of ketamine include decreased respiration and heart rate, increased blood pressure, and the possibility of vomiting and convulsions. These can lead to cardiac and respiratory arrest, coma, and death. The risk of ketamine overdose is much greater when it is mixed with other drugs such as alcohol, Ecstasy, caffeine, or cocaine. Overdoses of ketamine have been reported when people boost the drug (take another dose before the first dose wears off) to prolong its psychedelic effects. 

Most authorities believe caffeine and other analeptics should not be used in overdose with CNS depressants and recommend other supportive therapy... 

In low and moderate doses, the methylxanthines—especially caffeine—cause mild cortical arousal with increased alertness and deferral of fatigue. The caffeine contained in beverages—eg, 100 mg in a cup of coffee—is sufficient to cause nervousness and insomnia in sensitive individuals and slight bronchodilation in patients with asthma. The larger doses necessary for more effective bronchodilation commonly cause nervousness and tremor in some patients. Very high doses, from accidental or suicidal overdose, cause medullary stimulation and convulsions and may lead to death. 

Although rare, it is possible to overdose on caffeine. In the late 1990s, a North Carolina community college student swallowed almost 90 caffeine pills (equivalent to about 250 cups of coffee) and later died as a result. 

Caffeine cannot sober a drunk or save someone who is lethargic or unconscious from an overdose of a sedating drug. However, because caffeine lowers stomach pH, it can affect the absorption of other substances. Other drugs such as oral contraceptives, cimetidine, disulfiram, and alcohol can delay the body s ability to rid itself of caffeine. 

Brown CR. Caffeine. In Olson KR, Becker CE, Benowitz NL, Buchanan JF, Mycroft FJ, Osterloh J, Woo OF, eds. Poisoning and Drug Overdose. Norwalk, CT Appleton Lange, 1990 100-102. 

Tolerance and dependence. The regular, frequent use of caffeine-containing drinks is part of normal social life and mild overdose is common. Slight tolerance to the effects of caffeine (on all systems) occurs. Withdrawal symptoms, attributable to psychological cmd perhaps mild physical dependence... 

Chronic overdose. Excessive prolonged consumption of caffeine causes anxiety, restlessness, tremors, insomnia headache, cardiac extrasystoles and confusion diarrhoea may occur with coffee and constipation with tea. The cause can easily be overlooked if specific enquiry into habits is not made including children regarding cola drinks. Of coffee drinkers, up to 25% who complain of anxiety may benefit from reduction of caffeine intake. An adult heavy user may be defined as one who takes more than 300 mg caffeine/day, i.e. 4 cups of 150 ml of brewed coffee, each containing 80 20 mg caffeine per cup or 5 cups (60 20) of instant coffee. The equivalent for tea would be 10 cups at approximately 30 mg caffeine per cup and of cola drinks about 2.01. Plainly, caffeine drinks brewed to personal taste of consumer or vendor must have an extremely variable concentration according to source of coffee or tea, amormt used, method and duration of brewing. There is also great individual variation in the effect of coffee both between individuals and sometimes in the same individual at different times of life (see Sleep, above). 

The hypotension that has been noted with overdoses of caffeine is primarily due to two mechanisms. First, caffeine-induced tachydysrhythmias lead to inadequate filling of the heart and subsequent decrease in cardiac output. Second, caffeine augments S2-effects and causes subsequent vasodilation with resulting hypotension. 

Caffeine in overdose also acts as a nonselective antagonist of neuronal adenosine receptors that may lead to seizures. Caffeine is also a mild diuretic and it stimulates gastric acid secretion, respiration, and lipolysis. 

Systemically it is a stimulant to all parts of the central nervous system including the brain, the spinal cord, and the medulla. Its effects upon the brain are shown by an exaltation of the intellectual faculties similar to that which is produced by caffeine. In overdose it produces a delirium somewhat suggesting that of atropine, to which it is chemically related Its action upon the spinal cord is shown by increased activity of the reflexes but the convulsions which are seen in cocaine poisoning both in the lower animals and in man seem to be due to an action upon... 

The half-life of caffeine in humans is approximately 3.5 to 5 hours. It is metabolized extensively according to a complex metabolic pathway occurring primarily in the liver. Serious problems rarely result from overdoses of caffeine. In fact, the amount of caffeine needed to cause death in an average adult male is 5 to 10 g, the equivalent of 50 to 100 cups of regular brewed coffee. Thus the risk of overdose from dietary sources of caffeine is virtually nonexistent. 

Garriott JC, Simmons LM, et al. Five cases of fatal overdose from caffeine-containing "look-alike" drugs. J Analyt Toxicol 1985 9 141-3. 

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