Caffeine and Methylxanthines Escandell caffeine and methylxanthines 1

Caffeine and Methylxanthines Escandell caffeine and methylxanthines 1

Caffeine • • Xanthine stimulants and methylxantines theophylline and theobormine Coffee, tea, and chocolate Soft drinks Pain killers Cold remedies Stimulant caffeine and methylxanthines 2

Sources of Methylxanthines • Coffea (genus) – Arabica – Canephora (robusta) 2 x caffiene of arabica caffeine and methylxanthines 3

caffiene • Caffeine concentration of the coffee bean • Method brewing • The size of the cup (5 oz or 20 oz. ) • 8 oz cup = 133 mg avg. caffeine and methylxanthines 4

Caffeine concentration caffeine and methylxanthines 5

TEA • Leaves of camellia sinensis • Best is bud and first two leaves; caffeine content goes down as move down the bush/tree. • Black tea: leaf is crushed, fermented (oxydized) • Oolong fermentation stoped and roasted • Green tea unfermented add aromatics (jasmine) • Average caffeine is 27 mg. per 5 oz. 8 -91 mg. caffeine and methylxanthines 6

cocoa • • • COCAO tree theobroma cacao Cocoa is term used to refer to the processed products of the bean. NOT COCA = cocaine Cultivated C and S America, Africa, W Indies Tree grows seedpods from trunk and main branches. 6 -10” long and 3 -4 “ in diameter with 20 -40 seeds and pulp. Ferments, germinates, dies and dried. Roasted crushed, and sold as unsweetened chocolate (high fat content). Alkalized to mix with water. caffeine and methylxanthines 7

Guarana & Holly cassina • Black drink, cassina tea, yaupon, • Guarana of Paullinia cupana is 2 -6% caffeine ( most potent of natural sources of caffeine). Amazon and Negro river made into paste. Shapes sweetened with sugar. Added to energy drinks. caffeine and methylxanthines 8

Ilex plant and cassina • Types of holly • Ilex paraguariensis Mate =5 cups of coffee. Vomit so not poisoned caffeine and methylxanthines 9

Cola • Southern Nigeria and western Africa • Into cola from edible nuts often chewed caffeine and methylxanthines 10

Caffeine added • • • For flavor analgesics Weight control Allergy relief Stimulants Respiratory stimulants Asthma caffeine and methylxanthines 11

Soft drinks and Energy Drinks • Caffeine in soft drinks 35 - 50 mg • Jolt has 71 mg. • Energy drinks or dietary supplements 50 -300 mg of caffeine • Add ginkgo, guarana, kola nut, mate and coca so amt is unknown. caffeine and methylxanthines 12

Tea • Cultivated in 780 A. D. • 1760 tea is 3 rd largest export in colonies caffeine and methylxanthines 13

Rank Country[78] 1 China 2 2008 2009 2010 2011 1, 274, 984 1, 375, 780 1, 467 1, 640, 310 India 987, 000 972, 700 991, 180 1, 063, 500 3 Kenya 345, 800 314, 100 399, 000 377, 912 4 Sri Lanka 318, 700 290, 000 282, 300 327, 500 5 Turkey 198, 046 198, 601 235, 000 221, 600 6 Vietnam 173, 500 185, 700 198, 466 206, 600 7 Iran 165, 717 162, 517 8 Indonesia 150, 851 146, 440 150, 000 142, 400 9 Argentina 80, 142 71, 715 88, 574 96, 572 10 Japan 96, 500 86, 000 85, 000 82, 100 Total World 4, 211, 397 4, 242, 280 caffeine and methylxanthines 4, 518, 060 4, 321, 011 14

Chocolate • Caffeine and theobromine • 1 oz of semisweet has 150 to 300 mg of methylxanthines • Cup hot chocolate has 75 to 100 mg caffeine and methylxanthines 15

Methylxanthines • Highly traded • Of agricultural and food it is fifth behind meat dairy and vegetables and slighly behind fish. • Average caffeine is 70 mg – 90% is tea or coffee. • Scandinavian drink 7 -9 kg of coffee beans • N. America Canada 6. 3 kg and USA 4. 1 kg • Elders= coffee and tea; younger= colas caffeine and methylxanthines 16

Route of administration • Orally without difficulty except children then suppository or IV caffeine and methylxanthines 17

Absorption • • Wall of intestine reduced by food Bases - Low p. Ka 0. 5 Lipid soluble and dissolves poorly in water Dissolved in alkaloid form • As medicine given as salts Aminophylliine for asthma • Completely absorbed within 30 minutes with peak at 1. 5 to 2. 0 hrs. caffeine and methylxanthines 18

Excretion • • • <2 % excreted in urine Converted to paraxanthine metabolite in liver. Half life is constant from 2. 5 to 4. 5 hrs The larger the dose the longer the half life. Individual genetic differences CYP 1 A 2 = rapid and slow metabolizers • Half life longer in lutreal phase (after ovulation) • Newborns cannot metabolize caffeine • Other species different from humans caffeine and methylxanthines 19

neurophysiology • Adenosine receptor blockers • Adenosine functions as neurotransmitter at postsynaptic synapses and Neuromodulators at presynaptic by inhibiting the release of neurotransmitters in many synapses of the brain. • Modulate dopamine in brain • Behavioral and reinforcing effects of methylxanthines • Block benzodiazepines receptors no r with drug’s effects on behavior. caffeine and methylxanthines 20

Effects on body • Release adrenal gland epinephrine therefore sympathetic nervous system arousal. • Caffeine effect on muscles. Smooth (involuntary) tend to relax and striated voluntary muscles are strengthened. • Therefore dilation of bronchi of lungs and decrease in airway resistance Theophylline most potent • Reduce striated muscle fatigue caffeine and methylxanthines 21

Caffeine differential blood flow • Brain restricted : . Lessens HA • Dilation in rest of body • High levels stimulate the spinal cord. • Increase in excitability of spinal reflexes, convulsions increase in rate and depth of breathing caffeine and methylxanthines 22

Human performance • • Improved cognitive function at low dose Improves mood and makes tasks easier Subjects assessment not r with behavior Reverses decrements caused by boredom and fatigue, drug caffeine withdrawal and common cold. • Improve alertness, attention, working memory, caffeine and methylxanthines 23

Athletic performance • Improve performance in submaximal effort as cross country skiing, running, cycling. • Lowers threshold for exercise induced beta endorphin and cortisol release on exercise endurance • Was banned in Olympics until 2004 caffeine and methylxanthines 24

Effects on sleep • Methylxanthine produces insomnia • Reduces time to fall asleep and reducing total sleep time, feel less rested. caffeine and methylxanthines 25

Unconditioned behavior • Decrease spontaneous motor activity (SMA) • Chronic tx with caffeine decreases sma • automutilation caffeine and methylxanthines 26

Operant and respondent • Increases avoidant responding caffeine and methylxanthines 27

Subjective effects • Positive effects in coffee abstainers • More likely to be seen at low doses • Increase (178 Mg) in well being, magnitude of drug effect, energy, affection for loved ones, motivation at work, self confidence, social disposition, alertness, and concentration and decreases in sleepy and muzzy feelings. For 30’ to 8 hours. caffeine and methylxanthines 28

tolerance • Chronic administration produces up regulation of adenosine receptors after exposure to caffeine, a six fold increase in dose was required to produce the same effect as before the exposure. • Individuals who are resistant to effects of caffeine are ones who become heavy drinkers. caffeine and methylxanthines 29

withdrawal • Decrease in locomotor activity and disruption of ongoing operant responding. • HA most common sx • Decreased motivation, decreased energy, impaired concentration, decreased feelings of well being and self confidence, hot and cold spells and heavy feelings. caffeine and methylxanthines 30

Dependence • Dose 600 mg per day after only 6 - 14 days or 100 mg day for longer periods. • No placebo effect caffeine and methylxanthines 31

Self administration • Not able to show consistent reinforcing effect of caffeine and methylxanthines 32

Harmful effects • At high levels damages chromosomes • Low levels damage both fetus and retard growth or lower birth weight by 161 g. • Cardiac disease heart attack increased by caffeine. • Bone density • Caffeinism and anxiety sensory disturbances, ringing in th ears, and seeing flashes of light as well s mild delirium and excitement. • Caffeine induces anxiety caffeine and methylxanthines 33

Beneficial effects • Protective against Parkinson's disease • Weight loss • Lobbyists groups fake evidence caffeine and methylxanthines 34

methylxanthines • Studies reported in 2008, based on 12 C/13 C isotopic ratios of organic compounds found in the Murchison meteorite, suggested that xanthine and related chemicals, including the RNA component uracil, were formed extraterrestrially. [3][4] In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting xanthine and related organic molecules, including the DNA and RNA components adenine and guanine, were made in outer space. [5][6][ caffeine and methylxanthines 35

Selected Xanthines Name R 1 R 2 R 3 R 8 IUPAC nomenclature Xanthine H H 3, 7 -dihydro. Plants, animals purine-2, 6 -dione H 1, 3 dimethyl 7 H-purine 2, 6 -dione Tea, Cacao (chocolate), Yerba mate, Kola H 3, 7 -dihydro -3, 7 dimethyl 1 H-purine 2, 6 -dione Cacao (chocolate), Yerba mate, Kola, Guayusa, Yaupon holly H 1, 7 dimethyl 7 H-purine 2, 6 -dione Animals that have consumed caffeine Coffee, Guarana, 1, 3, 7 Yerba trimethylmate, Tea, 1 H-purine. Kola, 2, 6(3 H, 7 H)Guayusa, dione Yaupon holly Theophyllin CH 3 e Theobromi ne Paraxanthi ne Caffeine H CH 3 H H CH 3 CH 3 H 8 Chlorotheo CH 3 phylline CH 3 H Cl caffeine and methylxanthines Found In Dimenhydri nate 36

references • Mckim, W. A. , and Hancock S. D. (2012) Drugs and Behavior. Boston: Pearson caffeine and methylxanthines 37