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PYB260 > Week 4 - Caffeine > Flashcards

Week 4 - Caffeine Flashcards

1
Q

What class of drugs does caffeine belong to?

A

Methylxanthines

  • occur naturally
  • most widely used psychoactive drug in the world
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2
Q

What are the sources of caffeine?

A
  • Coffee
  • Tea
  • Chocolate
  • Medication
  • Soft drinks and other foods
  • New forms - e.g. strips
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3
Q

What is caffeine’s route of administration?

A

o Normally taken orally, but can be i.m. or i.v.
o When given for medical reasons methylxanthines given as salts rather than alkaloids – more readily/quickly absorbed (e.g. Aminophylline as bronchodilator for asthma)

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4
Q

How is caffeine absorbed?

A

o Methylxanthines readily dissolve in any tissue & are quite lipid-soluble
o Typically absorbed from stomach & through intestinal walls; absorption occurs directly from digestive system with little first-pass metabolism

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5
Q

What is the pKa?

A

pH when 1/2 molecules are ionized

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6
Q

How does caffeine’s pKa effect it’s absorption

A

because it is a very low pKa it means that it would have to be very acidic to be ionized – so it gets absorbed very easily because it isn’t ionized

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7
Q

How is caffeine distributed?

A

o Caffeine crosses the blood-brain barrier and placental barriers (thus reaches all organs in the body)
o Present in all bodily fluids
o Theophylline & theobromine less lipid soluble vs. caffeine

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8
Q

When do caffeine levels peak and what can affect this ?

A

• Peak caffeine levels reached 30-60 minutes after oral admin
o Many factors can affect absorption time (e.g. coffee – 30 min; chocolate – 1.5-2 hrs – sugar and fat slows absorption)
• Stomach content is important

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9
Q

What is the half life of caffeine/

A

3.5 hrs, but may be dose dependent

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10
Q

How is caffeine excreted, and how much?

A
  • <2% excreted unchanged in urine in adults*; most caffeine is converted to different metabolites
  • Caffeine does not accumulate over long periods of time, if not consumed > 6pm
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11
Q

How does excretion change for newborns?

A

*Newborns (<7-9 months)
o Excrete – 85% of caffeine unchanged -> half-life of caffeine is approx. 4 days
o Remainder excreted following different metabolic pathways then adults

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12
Q

What are some factors that heighten caffeine metabolism?

A

Genetic differences (CYP1A2 gene)

  • Higher caffeine metabolism
  • Gender (hormones in women - pre-menstruation phase met faster)
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13
Q

What are some factors that may lower caffeine metabolism?

A 
o	Alcohol 
o	Grapefruit juice 
o	Oral contraceptives 
o	Pregnancy 
o	Some antibiotics
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14
Q

What is the effect of caffeine at usual doses?

A

o Methylxanthines primarily act as antagonist (blockers) of adenosine receptors – esp. A1 & A2A subtypes, which interact with dopamine (DA) receptors
o Adenosine: inhibits the firing of neurons; & blocks the release of many NTs (e.g., Ach, NE, DA, GABA, 5-HT)

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15
Q

What does caffeine do at usual doses?

A

causes release of epinephrine & other catecholamines from brain tissue & adrenal glands  may contribute to stimulating effect (SNS)

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16
Q

What does caffeine do at high doses?

A

blocks benzodiazepine receptions (may explain increased anxiety seen at high doses)

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17
Q

What does chocolate contain?

A

substances that resemble anandamide (endogenous substances that work at cannabinoid receptors)
o Other compounds in chocolate block its metabolism

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18
Q

What happens in the nervous system?

A

• Release of adrenalin -> stimulation of the sympathetic NS

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19
Q

What happens in the spinal cord?

A
  • At high levels spinal reflexes more excitable

* Higher doses -> convulsions (poss. Death)

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20
Q

What happens in the medulla?

A

• Regulatory centers stimulated  increased rate & depth of breathing (medications for newborns who have trouble breathing)

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21
Q

What happens in the 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
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22
Q

What is the effect on the muscles?

A

• Most effects outside the CNS are due to effect in muscles
o Smooth muscles relax – theophylline & bronchi
o Striated muscles strengthen – increased fatty acids & decreases fatigue in muscles; caffeine in sport (banned in some that require endurance – doesn’t have as much of an effect for short burst sports)

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23
Q

What are the effects of caffeine on behaviour at low-moderate doses?

A

o Caffeine usually thought to increase alertness, concentration, endurance, sensory sensitivity ect. (Subjective perception)
o Mixed research results (? Due to methodological problems/poor experimental design)

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24
Q

What are some methodological considerations of caffeine research?

A 
o	Dose 
o	Time of consumption 
o	Nature of the task 
o	Individual differences 
	Personality 
	Age 
	Usual caffeine consumption 
	Tolerance ect.
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25
Q

What are the conditions needed for detection of positive effects?

A
  • Low doses (20-200 mg)
  • Non-habitual caffeine users (effects in such users suggest not due to alleviation of withdrawal symptoms)
  • If caffeine is a positive reinforcer for participants
26
Q

What are the effects of caffeine on sleep

A

fall asleep and decrease total sleep time

• People also wake more easily, as caffeine decreases acoustic arousal thresholds

27
Q

What drug does caffeine counter the effect of

A

Pentobarbital

28
Q

What is caffeine’s effects as a fat releaser?

A

 May be mechanism of breaking down fat into fuel to be used – but problem is that you need to engage in vigorous exercise to make that work

29
Q

What is caffeine’s effects as a metabolism activator?

A

 Possibly that because of increase in adrenaline – but effect size was incredible small

30
Q

What is caffeine’s effect as an appetite suppressant?

A

 Because of effect on thalamus – but no evidence yet

o BUT study was inconclusive – didn’t necessarily found effects

31
Q

What does caffeine stimulate?

A

• Stimulation of urination and defecation

o Kidneys and colon: adenosine receptors

32
Q

What does caffeine and theophylline increase in animals?

A

increases SMA (dose-dependent effect – max approx. 20-40 mg/kg), but long term treatment decreases SMA

33
Q

What is the LD50 for rats and mice?

A

250 mg/kg i.p.

34
Q

What may result from high dose in animals

A
  • Death may result from convulsions, but long term treatment decreases seizure sensitivity
  • Auto-mutilation can cause death in animals exposed to caffeine at larger doses (e.g. 185 mg/kg for 14 days
35
Q

What are caffeine’s effects on conditioned responses?

A
  • Pavlov (1927): caffeine increases responses to negative stimuli, therefore interrupting conditioning experiments
  • Caffeine appears to increase avoidance responding
  • Response profile of caffeine on operant conditioning is similar to those of amphetamine for some behaviors but v. different for others
36
Q

Can rats discriminate caffeine from saline?

A

At 32 mg/kg

37
Q

Can animals generalize caffeine

A

@ lower doses of caffeine & higher doses theophylline but not to nicotine
• Partial generalization to cocaine & amphetamines if trained to discriminate low doses =

38
Q

What are turkey drugs?

A

caffeine-based amphetamine look-alike drugs can mimic discriminative stimulus effects of cocaine

39
Q

Can humans discriminate caffeine?

A

• Humans can also discriminate caffeine at low doses, but this may not generalize to theobromine

40
Q

Do people get tolerance to caffeine?

A

• Chronic caffeine administration causes increases (up regulation) in adenosine receptors –> tolerance

41
Q

When does tolerance show for different effects?

A

o Cardiovascular: 2-5 days
o Increased urine output: never?
o Sleep: 7 days

42
Q

What are the withdrawal effects in humans?

A
  • Headache
    fatigue, drowsiness, lethargy, decreased motivation, irritability, decreased self-confidence, flu-like symptoms
    • Symptoms closely related to dose
43
Q

What is a withdrawal effect in animals?

A

• Lower locomotor activity; disruption of ongoing operant responding

44
Q

When does physical dependence occur and at what dose?

A

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

45
Q

When do withdrawal symptoms start? How long can they last?

A

< 12-24 hrs of abstinence and can last up to a week

46
Q

What percentage of coffee drinkers who abstain experience withdrawal?

A

• 27-57%

47
Q

What is the self administration tendency in animals?

A

• Self-administration is variable and inconsistent; with no tendency to increase dose over time

48
Q

What is the self administration tendency in humans?

A
  • Reinforcing properties vary considerably between individuals
  • Preference may be determined by level of dependence (i.e. withdrawal symptoms)
49
Q

What is the self administration tendency in general?

A
  • Caffeine s.a. related to state of physical dependence
  • High doses less reinforcing than lower doses
  • Preference may be context dependent
50
Q

What is the common belief about caffeine’s counteractive effects?

A
  • Belief that caffeine can counteract the effects of sedative-hypnotic drugs
51
Q

What is the truth about caffeine’s counteractive effects?

A

o Empirical evidence is equivocal
o Still have lack of co-ordination
o And complex decision making is still impaired
o But has some effects to make you feel better

52
Q

What common drug does caffeine show interesting reactions to?

A

Nictoine

53
Q

What are the interactions that caffeine has with nicotine?

A
  • May enhance reinforcing and subjective stimulant qualities of nicotine in humans
  • Smokers metabolise caffeine quicker than nonsmokers
  • Smoking cessation –> caffeine consumption increase by greater than 200%
54
Q

What are the harmful effects of caffeine on reproduction?

A
  • Chromosomal damage at v. high doses
  • Increased chromosomal damage caused by other agents (e.g., radiation)
  • Retards growth in the fetus and lowers birth weight
  • Increased risk of miscarriage???
  • Possible adverse effects on sperm motility/morphology
  • Potentiates effect of smoking
  • Rate of metabolism slows with pregnancy – baby gets higher and higher doses of caffeine
  • Methylxanthines in breast milk can reach toxic levels (v. slow metabolism in newborns)
55
Q

What are the harmful effects of caffeine on the heart?

A
  • Increased BP
  • Heart disease/attacks?
  • -> CP1A2 gene may slow metabolism
  • Boiled coffee may increase cholesterol
56
Q

What are the harmful effects of caffeine to do with cancer?

A
  • Animal studies do not support association
  • May increase effect of other agents which cause cancer
  • Duration of use rather than amount used may be crucial
  • May interact with smoking to cause pancreatic cancer
57
Q

What abnormal behaviour can caffeine cause?

A

• Caffeinism: results at 5-10 cups per day
o Sensory disturbance, delirium, fever, insomnia, irritability, irregular heartbeat, psychomotor agitation
• DSM-V: “caffeine intoxication” & “caffeine withdrawal”
• Panic attacks & increased anxiety
o From caffeine blocking benzodiazepine receptors
o Caffeine may also decrease effectiveness of some antipsychotics (e.g., chlorpromazine)

58
Q

What effects does caffeine have on bone density?

A

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

59
Q

What dose of caffeine is lethal?

A
  • Lethal dose is 30-80 cups of coffee (3-8 grams of caffeine) taken orally
  • Death results from respiratory collapse & convulsions
60
Q

What can high caffeine intake cause to do with psychopathology?

A

• High caffeine intake:
o May be misdiagnosed as an anxiety disorder
o Can cause agitation & hyposomnia which can lead to diagnosis of bipolar disorder
o Reported to exacerbate psychosis
• Caffeine may be a complicating factor in anorexia nervosa
• Caffeine may interact with psychotropic medications incl. antidepressants (tricyclics & SSRIs)

PYB260 (9 decks)

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