Caffeine Pharmacology

By Dr Ananya Mandal, MD

Caffeine is a stimulant of the central nervous system that occurs naturally in over 60 species of plants and is used in several foods, drinks and medications. The United States Food and Drugs Administration classes caffeine as both a food additive and a drug.

Pharmacokinetics

The half-life of caffeine (time taken for the body to eliminate one-half of the caffeine) varies widely between people, depending on factors such as age, body weight, pregnancy status, medication intake and liver health. In healthy adults, the half-life is approximately 5 to 6 hours. Heavy cigarette smoking can decrease the half-life of caffeine by up to a half and in pregnancy, the half-life may be increased by as much as 15 hours.

Caffeine is processed or metabolized in the liver by the cytochrome P450 oxidase enzyme system and broken down into three metabolic dimethylxanthines. These include:

  1. Paraxanthine (forms 84%), which breaks down fats and increases blood levels of glycerol and fats.
  2. Theobromine (forms 12%), which dilates blood vessels and also has a diuretic effect, increasing urination.
  3. Theophylline (forms 4%), which dilates the airways and is used in the treatment of asthma.

These metabolites are then further broken down and excreted in the urine.

Caffeine crosses the blood-brain-barrier, which is designed to separate the brain from the bloodstream. Once inside the brain, caffeine blocks the effects of adenosine, which plays an important part in energy transfer and sleep promotion. 

Caffeine’s effects on the body

The stimulatory effects of caffeine may begin as early as 15 minutes after ingesting the drug and last as long as six hours. In moderate doses, caffeine helps to increase alertness and reduces sleepiness. However, regular ingestion of excess amounts of caffeine can lead to problems such as poor concentration, nervousness, heartburn, constipation and diarrhea. Longer-term effects may include sleep deprivation, impaired judgement, emotional fatigue, mood swings, depression and anxiety.

Symptoms of excess caffeine use

Some examples of the symptoms that may occur in people who consume too much caffeine include:

  • Anxiety
  • Confusion
  • Irritability
  • Suppressed appetite
  • Sleeplessness
  • Dizziness
  • Blurred vision
  • Dry mouth
  • Increased thirst
  • Flushed skin
  • Cold sweats
  • Pale and clammy appearance
  • Rapid heart rate and palpitation
  • High blood sugar
  • Breathing difficulty
  • Tremors
  • Heartburn
  • Stomach ache
  • Nausea and vomiting
  • Diarrhea
  • Increased urination
  • Presence of ketones in the urine

Withdrawal symptoms

If stopped abruptly, caffeine may also give rise to withdrawal symptoms. Examples of these include:

  • Irritability
  • Headaches
  • Loss of concentration
  • Sleepiness in presence of insomnia
  • Stomach pain

These effects may appear within 12 to 24 hours after stopping caffeine intake and last for 5 to 7 days. Analgesics such as aspirin can help to relieve these symptoms.

Caffeine uses

Some examples of the benefits people experience with caffeine intake include:

  • Overcoming sleep deprivation – Caffeine can increase alertness and reduce sleepiness
  • Mental acuity – Caffeine is though to boost concentration and working memory
  • Physical performance – Caffeine can enhance physical performance, reducing perception of muscle pain and increasing energy.
  • Headache reliever – Blood vessels often dilate during a headache and as a vasoconstrictor, caffeine is thought to be useful for easing headaches.
  • Studies have demonstrated that the regular, moderate consumption of caffeine may prevent gallstones.
  • Caffeine may also play a preventative role in the development of Parkinson’s disease and Alzheimer’s disease.

When to avoid caffeine

Caffeine intake should be avoided by pregnant women. Excessive caffeine intake during pregnancy has been linked to low birth weight, premature delivery and miscarriage. The FDA advises that pregnant women should avoid or strictly limit caffeine-containing foods and drugs.

Caffeine intake should also be avoided in the following health conditions:

  • Sleep disorders
  • High blood pressure
  • Liver or kidney disease
  • Anxiety or depression
  • Gastroesophageal reflux disease

Reviewed by , BSc

Further Reading

Last Updated: May 2, 2014

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Comments
  1. Kari Luoto Kari Luoto Finland says:

    Caffeine is metabolized mostly to uric acids.
    www.genome.jp/dbget-bin/www_bget?pathway+hsa00232

    Caffeine accumulates in the body and if you use it on daily basis, you have caffeine and its active metabolites in the blood 24/7.
    35% of caffeine binds to proteins and is not in the blood circulation.
    http://www.ncbi.nlm.nih.gov/pubmed/2060564

    Because caffeine is metabolized mostly to uric acids and caffeine accumulates in the body, it is safe to assume that caffeine accumulates in the body as different caffeine uric acids.

    Why is it then that these caffeine uric acids are not being removed from the blood to urine? Isn't that what kidneys are supposed to do? What can stop kidneys from secreting uric acids from blood to urine?

    "Physiologically, the major factors that affect urate excretion are the tubular fluid pH, the tubular fluid flow rate, and renal blood flow. The first 2 factors primarily diminish uric acid and urate precipitation in the collecting ducts, while the third is important in urate secretion. In disorders such as sickle cell disease, hypertension, and eclampsia, hyperuricemia out of proportion with decreases in glomerular filtration result from decreased renal blood flow. Organic acids, such as lactic acid and ketoacids, also can impair the proximal secretion of uric acid."
    emedicine.medscape.com/.../244255-overview#a0104
    http://www.ncbi.nlm.nih.gov/pubmed/3721778

    The major factor is the effect of caffeine to blood circulation. Caffeine inhibits adenosine which is the most important neurotransmitter that dilates the blood vessels. Caffeine releases stress hormones that constrict blood vessels and reduce renal blood flow, inhibiting the secretion of uric acids to urine. The fact that caffeine's pharmacodynamic effects are mainly based on chronic elevation of stress hormones, makes it a systemic toxin that alters the chemical balance of every cell, and can thereby cause drastic changes in body's processes and organ functions.
    http://www.ncbi.nlm.nih.gov/pubmed/11815511

    Uric acids are poorly water soluble. When they enter tissues with reduced water flow, the concentration elevates locally and the acids start to crystallize. Such tissues are bone, connective tissue between skeletal muscles and bones and fat. When blood UA concentration gets too high, blood can no longer melt crystallized acids. It is known that caffeine lowers the blood uric acid concentration, but reason to this is not known.
    http://www.ncbi.nlm.nih.gov/pubmed/17530681

    This video shows two different modes of accumulation in big toe. First between the bone and soft tissue starting from the second joint to both directions. The second view is from the side of the toe, where uric acids have started to crystallize downward from the joint, forming a large blister under the toe. This is same mechanism applies in the whole body.
    http://www.youtube.com/watch?v=TB1un6xzlRI


    Caffeine metabolites stored in the body have very similar sympathomimetic effects with caffeine.
    http://www.ncbi.nlm.nih.gov/pubmed/8529334

    Crystallized uric acids are not stable. They can start melting from one point or another for various reasons, creating an acute caffeine poisoning that can be lethal. The problem with diagnosing the symptoms caused by these toxins is that they can cause systemic symptoms with high concentration and local peripheral symptoms close to an infected deposit, and central nervous system symptoms with two different mechanisms; generally elevated UA concentration, and locally elevated concentration in brain due to local melting in small scale. The latter one can create extremely bizarre physical symptoms depending on the location of meltdown.

  2. june buie june buie United States says:

    Thank you, thank you, thank you for the information on the effects of caffeine and what you call "TOT" episodes.  I am over 55 and I am an avid coffee drinker. I have been experiencing loss of words mid way through my sentences as well as having numerous loss of words, and remembering names.  I drink about 23 oz a day and then I'm through. I am going to lessen that amount each day and see what happens. I just can't STOP drinking it because I love it. I was looking really silly and I was worried. I'm relieved and now I know! Thank You!

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical.Net.
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