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PYB260 > Week 4 - Caffeine > Flashcards

Week 4 - Caffeine Flashcards

1
Q

What is the family of drugs that caffeine belongs to?

A

methylxanthines (xanthine stimulants)
- occur naturally
- most widely used psychoactive drugs in the world

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2
Q

Commonly self-administered methylxanthines

A
  • caffeine
  • theophylline (tea)
  • theobromine (chocolate)
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3
Q

less commonly self-administered methylxanthines

A
  • Ilex plant (amazon; mate)
  • guarana (south america)
  • kola nuts (west africa)
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4
Q

what year was caffeine first isolated from coffee

A

1820

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5
Q

sources of caffeine

A
  • coffee
  • tea
  • chocolate
  • medication
  • soft drinks & other foods
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6
Q

History of caffeine use

coffee

A
  • Ethiopia (12th and 15th centuries)
  • spread to europe
  • 1st english coffeehouse opened in Oxford in 1650
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7
Q

History of caffeine use

tea

A
  • china (780 A.D.)
  • europe imports (1606)
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8
Q

History of caffeine use

cocoa

A
  • mayas, aztecs, incas (pre-columbian)
  • cortez introduced chocolate drink to spain in 1520
  • 1728: 1st chocolate factory in england
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9
Q

Route of administration

A
  • orally, i.m. or i.v.
  • medically, given as salts rather than alkaloids - quickly absorbed
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9
Q

Caffeine content in food and drink

A

espresso - 145mg/50mL cup
energy drinks - 80mg/250mL can
instant - 80mg/ 250mL cup
tea - 50mg/220mL cup
coke - 36.4mg/375mL can
chocolate - 20mg/100g bar
no-doz - 100mg/tablet

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10
Q

absorption

A
  • methylxanthines dissolve in tissue (are lipid soluble)
  • absorbed from stomach & intestinal walls (little first-pass metabolism due to absorption from digestive system)
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11
Q

distribution

A
  • caffeine cross BBB & placental barrier (reaches all organs)
  • present in bodily fluids
  • theophylline & theobromine less lipid soluble vs caffeine
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12
Q

when are peak caffeine levels reached?

A

45-75 minutes after oral administration

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13
Q

excretion

A
  • half-life ~ 5 hours (dose dependent)
  • ~1% excreted unchanged in adult urine - most caffeine converted to different metabolites
  • caffeine does not accumulate over long periods of time, if not consumed >6pm
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14
Q

excretion

newborns

A
  • ~85% of caffeine unchanged
  • half life is 4 days
  • remained excreted following different metabolic pathways than adults
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15
Q

Factors that mediate caffeine metabolism

A
  • genetic differences - CYP1A2 gene: 1A = rapid, 1F = slow
  • increased caffeine metabolism:
  • > smoking
  • > broccoli
  • > hormone levels (in women)
  • decreased caffeine metabolism:
  • > alcohol
  • > grapefruit juice
  • > oral contraceptives
  • > pregnancy
  • > some antibiotics
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16
Q

Methylxanthines are antagonist to what?

A

adenosine receptors - esp. A1 & A2A subtypes, which interact with dopamine receptors

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17
Q

adenosine

A

inhibits the firing of neurons & blocks the release of many neurotransmitters

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18
Q

neurophysiological effects of caffeine at usual and high doses

A

usual: causes release of epinephrine & other catecholamines from brain tissues & adrenal glands - may contribute to stimulating effect (SNS)
high: blocks benzodiazephine receptors (may explain increased anxiety seen at high doses)

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19
Q

neurophysiological effects from chocolate

A

anandamide - endogenous substance that works at cannabinoid receptors - creating a ‘high’

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20
Q

physiological effects

nervous system

A

release of epinephrine - stimulation of sympathetic nervous system

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21
Q

physiological effects

spinal cord

A
  • at high levels spinal reflexes more excitable
  • higher doses - convulsions (possibly death)
22
Q

physiological effects

medulla

A

regulatory centres stimulated - increased rate and depth of breathing (medications for newborns)

23
Q

physiological effects

blood vessels

A
  • various effects depending on part of the body
  • constricts brain blood vessels, but dilates vessels in the rest of the body
  • headaches & headache tablets
24
Q

physiological effects

muscles

A

most effects outside the CNS are due to effect in muscles
- smooth muscles relax - theophylline & bronchi
- striated muscles strengthen - increased fatty acids and decrease fatigue in muscles; caffeine in sport

25
Q

caffeine on behaviour

A

caffeine is thought to increase alertness, concentration, endurance, sensitivity but there are mixed results. Some accounts reflect expectancies rather than genuine caffeine effects

26
Q

methodological considerations of caffeine research

A
  • dose
  • time of consumption
  • nature of the task
  • individual differences (personality, age, usual caffeine consumption, tolerance)
27
Q

conditions for detecting positive effects

A
  • low doses (20-200mg)
  • non-habitual caffeine users
  • if caffeine is a positive reinforcer for participants
28
Q

caffeine on sleep

A
  • methylxanthines can produce insomnia by increased time taken to fall asleep
  • people wake easily as caffeine decreases acoustic arousal thresholds
  • caffeine can counter the effects of pentobarbitual (sedative)
29
Q

caffeine on weightloss

A
  • correlation between amount of caffeine consumed and eating disorder patients
  • hypothesised caffeine is a fat releaser, metabolism activator and appetite suppressant
30
Q

caffeine on urination and defecation

A

stimulates due to antagonistic effects on adenosine receptors found in the kidneys and colon

31
Q

animal studies on caffeine

A
  • caffeine & theophylline increase spontaneous motor activity (dose dependent - max 20-40mg/kg), long term treatment decreases spontaneous motor activity
  • LD50 for rats and mice = 250mg/kg when administered intraperitoneal
  • death may results from convulsions, long term treatment decrease seizure sensitivity
  • auto-mutilation can cause death in animals exposed to caffeine at larger doses (185mg/kg for 14 days)
32
Q

conditioned responses

A
  • Pavlov - caffeine increases responses to negative stimuli, therefore interrupting conditioning experiments
  • caffeine increases avoidance responding
  • response profile of caffeine on operant conditioning is similar to those of amphetamine for some behaviours
33
Q

discriminative properties

A
  • rats can discriminate caffeine & saline at 32mg/kg
  • generalisation at lower doses of caffeine & higher doses of theophylline but not to nicotine
  • partial generalisation to cocaine & amphetamines if trained to discriminate low doses
  • Turkey drugs: caffeine based amphetamine look alike drugs can mimic discriminative stimulus effects of cocaine
  • humans can also discrimiate caffeine at low doses, but this may not generalise to theobromine
34
Q

Tolerance

A
  • chronic caffeine administration causes increased upregulation in adenosine receptors
  • many studies have shown that caffeine has less effect on heavy coffee drinkers
35
Q

tolerance at different rates

A

cardiovascular: 2-5 days
increased urine output: never
sleep: 7 days
subjective effects: 4 days

36
Q

withdrawal

in humans

A
  • most common, headache
  • fatigue
  • drowsiness
  • lethargy
  • decreased motivation
  • irritability
  • deceased self-confidence
  • flu-like symptoms
37
Q

withdrawal

in animals

A

caffeine withdrawal effects can be demonstrated
- decreased locomotor activity; disruption of ongoing operant responding

38
Q

how many mgs and days can cause physical dependence

A

600mg for >6-14 days; smaller doses over a longer period of time

39
Q

when do withdrawal symptoms start

A

<12-28 hours of abstinence, peak ~20-50 hrs, can last up to a week

40
Q

what percentage of coffee drinkers report withdrawal symptoms

A

27-57% who abstain for 24 hours

41
Q

what can withdrawal explain?

A
  • headaches, irritability
  • weekend headaches & feelings of illness on holidays/weekends
42
Q

Self-administration in animals

A
  • caffeine is not a robust reinforcer
  • variable and inconsistent; with no tendency to increase dose over time
  • does potentiate reinforcing effects of cocaine and will act as a primer for cocaine
43
Q

self-administration in humans

A
  • reinforcing properties vary considerably between individuals
  • preference may be determined by level of dependence
    generally:
  • self-administration related to state of physical dependence
  • high doses less reinforcing than lower doses
  • preference may be context dependent
44
Q

caffeine interaction with sedative-hypnotic drugs

A

evidence is equivocal on whether caffeine can counteract effects of sedative hypnotic

45
Q

caffeine interaction with nicotine

A
  • may enhance reinforcing & subjective stimulant qualities of nicotine in humans
  • smokers metabolise caffeine quicker than nonsmokers (smoking cessation increases caffeine levels when consumed)
46
Q

harmful effects

reproduction

A
  • chromosomal damage at very high doses
  • increased chromosomal damage caused by other agents
  • 200mg dose decreases placental blood flow by 25%
  • slows growth in the fetus & decreases birthweight (esp 1st trimester)
  • increases risk of miscarriage
  • potentiates effect of smoking
  • rate of metabolism slows with pregnancy
  • mathylxanthines in breast milk can reach toxic levels
47
Q

harmful effects

cardiac disease

A
  • increased blood pressure
  • heart disease
  • boiled coffee may increase cholesterol
48
Q

harmful effects

cancer

A
  • animal studies do not support association
  • may increase effect of other agents which cause cancer
49
Q

abnormal behaviour: caffeinism

A

results at 5-10 cups a day
sensory disturbance, delirium, fever, insomnia, irritability, irregular heartbeat, psychomotor agitation

50
Q

abnormal behaviour: panic attacks and anxiety

A
  • from caffeine blocking benzodiazepine receptors
  • caffeine may also decrease effectiveness of some antipsychotics
51
Q

harmful effects

Bone density

A

accelerated loss of bone density in postmenopausal women who consume less than recommended calcium dose

52
Q

harmful effects

lethality

A
  • lethal dose ~150-200mg/kg of body weight (30-80 cups of coffee taken orally
  • death results ffrom respiratory collapse and convulsions
  • australia has banned caffeine powders and highly concentrated caffeine products
53
Q

Psychopathology of caffeine use

A
  • High caffeine intake can be misdiagnosed as an anxiety disorder, can cause agitation and hyposomnia leading to diagnosis of bipolar disorder, can exacerbate psychosis
  • complicating factor in anorexia nervosa
  • interacts with psychotropic medications

PYB260 (10 decks)

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