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  • Caffeine Toxicity

    Here's a brief article about the effects of caffeine, and it's prevalence in consumer drinks. Be aware, you'll find caffeine and its analogues in many TCM medicines also, something to consider when in China, and thinking about "experimenting" with the traditional Chinese medicines.

    Caffeine (1,3,7-trimethylxanthine) is the most widely consumed stimulant drug in the world. It is present in a variety of forms: medications, coffee, tea, soft drinks, and chocolate. About 80% of adults in the United States consume caffeine in the form of coffee or tea on a daily basis. In quantities found in food and beverages, caffeine is unlikely to cause acute medical problems. However, caffeine is present in concentrated forms in over-the-counter products, such as alertness-promoting medications (eg, NoDoz, Vivarin), menstrual aids (eg, Midol), analgesics (eg, Excedrin, Anacin, BC Powder), and diet aids (eg, Dexatrim). Caffeine is also a component of prescription medications (eg, Fioricet, Cafergot), energy drinks, and herbal preparations.

    In 1989, the US Food and Drug Administration (FDA) limited the amount of caffeine in OTC products to a maximum of 200 mg/dose. The ingestion of such concentrated sources of caffeine is the general cause of acute caffeine toxicity. See the image below for caffeine equivalents of common products.

    Caffeine has differing CNS, cardiovascular, and metabolic effects based on the quantity ingested. Average doses of caffeine (85-250 mg, the equivalent of 1-3 cups of coffee) may result in feelings of alertness, decreased fatigue, and eased flow of thought. High doses (250-500 mg) can result in restlessness, nervousness, insomnia, and tremors. In high doses, caffeine can cause a hyperadrenergic syndrome resulting in seizures and cardiovascular instability.

    Because caffeine overdoses, intentional or unintentional, are relatively common in the United States, physicians and other medical personnel must be aware of caffeine toxicity to recognize and treat it appropriately.

    Caffeine, a methylxanthine, is closely related to theophylline. Caffeine is rapidly and completely absorbed from the GI tract; it is detectable in the plasma 5 minutes after ingestion, with peak plasma levels occurring in 30-60 minutes. The volume of distribution in adults is approximately 0.5 L/kg. Caffeine is primarily metabolized by the cytochrome P450 (CYP) oxidase system in the liver. The plasma half-life of caffeine varies considerably from person to person, with an average half-life of 5-8 hours in healthy, nonsmoking adults. Caffeine clearance is accelerated in smokers; clearance is slowed in pregnancy, in liver disease, and in the presence of some CYP inhibitors (eg, cimetidine, quinolones, erythromycin). In addition, the hepatic enzyme system responsible for caffeine metabolism can become saturated at high levels, resulting in a marked increase in serum concentration with small additional doses.

    Various mechanisms mediate the effects of caffeine in the human body. Caffeine directly stimulates respiratory and vasomotor centers of the brain and acts as an adenosine antagonist, resulting in peripheral vasodilatation and CNS stimulation. Caffeine is a potent releaser of catecholamines (norepinephrine and, to a lesser extent, epinephrine) that increases cardiac chronotropic and inotropic activity, bronchodilation, and peripheral vasodilatation. Caffeine is also a phosphodiesterase inhibitor. However, because extremely high concentrations of caffeine are required to inhibit this enzyme, whether this effect contributes to the clinical effects of caffeine in vivo is unknown.

    In addition to its cardiovascular effects, caffeine induces a number of metabolic changes, including hyperglycemia (by stimulating gluconeogenesis and glycogenolysis), increased renal filtration, ketosis, and hypokalemia. Caffeine is a potent stimulator of gastric acid secretion and GI motility.

    Death from caffeine toxicity is rare, but it has been reported due to dysrhythmias, seizures, and aspiration of emesis. Oral doses of caffeine greater than 10 g can be fatal in adults. The average daily adult intake should generally be less than 500 mg/d.

    Death is an uncommon result of caffeine poisoning.
    • Death due to dysrhythmias, seizures, and aspiration of emesis is reported.
    • Oral doses of caffeine greater than 10 g can be fatal in adults.
    • Of the 3343 cases of caffeine poisoning reported to the AAPCC-NPDS in 2009, no deaths were noted.


    According to the most recent AAPCC-NPDS data available, 1249 caffeine poisoning cases were in children younger than 6 years, with the remainder of the cases distributed almost evenly between patients aged 6-19 years (942 cases) and patients older than 19 years (985 cases).[1]

    Serum caffeine clearance is greatly decreased during the first 6 months of life.

    Caffeine doses of 78 mg/kg have caused serious adverse effects in young children.

    If acute caffeine ingestion is suspected, patients or their family members should be questioned about their use of prescription medications, OTC drugs, and illicit drugs. Patients and family members should be queried about the use of cocaine, amphetamines, methamphetamine, phencyclidine (PCP), antidepressants, asthma medications, thyroid medications, or anticholinergics (eg, OTC allergy medications).

    The patient and his or her family members or friends may be able to give a history of recent caffeine ingestion (ingestion of alertness-promoting OTC medications, caffeinated beverages, or diet medications) or a history of recent behavior compatible with such use (eg, the patient was trying to lose weight or taking stimulants to aid in working or studying). In an acute overdose, pill bottles found at the scene may provide a clue to what the patient ingested.

    When ingested chronically in excessive amounts, caffeine produces a specific toxidrome (caffeinism), which consists of primarily CNS, cardiovascular, and GI hyperstimulation.

    CNS features
    • Headache Lightheadedness

    • Anxiety, agitation

    • Tremulousness, perioral and extremity tingling (resulting from tachypnea-induced respiratory alkalosis)

    • Confusion, psychosis

    • Seizures

    • Cardiovascular features

    • Palpitations or racing heart rate

    • Chest pain

    • GI features

    • Nausea and vomiting

    • Abdominal pain

    • Diarrhea, bowel incontinence

    • Anorexia


    CNS findings
    • Anxiety, agitation

    • Tremors

    • Seizures

    • Altered mental status

    • Head, eyes, ears, nose, and throat findings

    • The pupils are dilated but reactive to light.

    • The thyroid should be examined because thyrotoxicosis may mimic caffeine toxicity.

    Cardiovascular findings
    • Characteristic finding is widened pulse pressure due to positive inotropic effect as well as vasodilatory effect of caffeine.

    • Sinus tachycardia, dysrhythmias (eg, premature ventricular contractions, supraventricular tachycardias [SVTs], ventricular rhythms)

    • Hypotension

    Respiratory finding
    • Tachypnea

    GI findings
    • Vomiting

    • Abdominal cramping

    • Hyperactive bowel sounds


    Chronic toxicity is generally encountered in people who have ingested higher doses of caffeine-containing compounds (alone or in combination) for various reasons. Patients may be unaware that some products contain caffeine or that high doses of caffeine can be harmful. Patients may ingest caffeine-containing analgesics for headaches, OTC caffeine-containing medications for dieting, or OTC medications for improving alertness while studying or working. In addition, people may drink caffeine in beverages such as coffee, tea, soft drinks, or energy drinks (eg, Red Bull, AMP Energy Drink, Rockstar, Monster) or take caffeine in herbal preparations.

    Acute toxicity can occur after intentional or unintentional ingestion. OTC alertness-promoting medications are often implicated in intentional overdoses.
    Certain medications, such as CYP inhibitors (eg, cimetidine) and oral contraceptives, impair caffeine metabolism.
    Caffeine clearance is reduced in patients with chronic liver disease, in pregnant women, and in infants.
    Caffeine clearance is increased in smokers. With a stable amount of ingestion, serum caffeine concentrations can double in patients who stop smoking.


    David Yew, MD;
    Experienced Community organizer. Yeah, let's choose him to run the free world. It will be historic. What could possibly go wrong...

    "You're just a jaded cynical mother****er...." Jeffpeg

    (more comments in my User Profile)
    russbo.com



  • #2
    Tremulousness, perioral and extremity tingling (resulting from tachypnea-induced respiratory alkalosis)




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