PYB260 > Week 4 - Caffeine > Flashcards

Week 4 - Caffeine Flashcards

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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
What are the conditions needed for detection of positive effects?
* 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
What are the effects of caffeine on sleep
fall asleep and decrease total sleep time | • People also wake more easily, as caffeine decreases acoustic arousal thresholds
27
What drug does caffeine counter the effect of
Pentobarbital
28
What is caffeine's effects as a fat releaser?
 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
What is caffeine's effects as a metabolism activator?
 Possibly that because of increase in adrenaline – but effect size was incredible small
30
What is caffeine's effect as an appetite suppressant?
 Because of effect on thalamus – but no evidence yet | o BUT study was inconclusive – didn’t necessarily found effects
31
What does caffeine stimulate?
• Stimulation of urination and defecation | o Kidneys and colon: adenosine receptors
32
What does caffeine and theophylline increase in animals?
increases SMA (dose-dependent effect – max approx. 20-40 mg/kg), but long term treatment decreases SMA
33
What is the LD50 for rats and mice?
250 mg/kg i.p.
34
What may result from high dose in animals
* 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
What are caffeine's effects on conditioned responses?
* 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
Can rats discriminate caffeine from saline?
At 32 mg/kg
37
Can animals generalize caffeine
@ lower doses of caffeine & higher doses theophylline but not to nicotine • Partial generalization to cocaine & amphetamines if trained to discriminate low doses =
38
What are turkey drugs?
caffeine-based amphetamine look-alike drugs can mimic discriminative stimulus effects of cocaine
39
Can humans discriminate caffeine?
• Humans can also discriminate caffeine at low doses, but this may not generalize to theobromine
40
Do people get tolerance to caffeine?
• Chronic caffeine administration causes increases (up regulation) in adenosine receptors --> tolerance
41
When does tolerance show for different effects?
o Cardiovascular: 2-5 days o Increased urine output: never? o Sleep: 7 days
42
What are the withdrawal effects in humans?
- Headache fatigue, drowsiness, lethargy, decreased motivation, irritability, decreased self-confidence, flu-like symptoms • Symptoms closely related to dose
43
What is a withdrawal effect in animals?
• Lower locomotor activity; disruption of ongoing operant responding
44
When does physical dependence occur and at what dose?
600 mg/day > 6-14 days; smaller doses over a longer period of time
45
When do withdrawal symptoms start? How long can they last?
< 12-24 hrs of abstinence and can last up to a week
46
What percentage of coffee drinkers who abstain experience withdrawal?
• 27-57%
47
What is the self administration tendency in animals?
• Self-administration is variable and inconsistent; with no tendency to increase dose over time
48
What is the self administration tendency in humans?
* Reinforcing properties vary considerably between individuals * Preference may be determined by level of dependence (i.e. withdrawal symptoms)
49
What is the self administration tendency in general?
- Caffeine s.a. related to state of physical dependence - High doses less reinforcing than lower doses - Preference may be context dependent
50
What is the common belief about caffeine's counteractive effects?
- Belief that caffeine can counteract the effects of sedative-hypnotic drugs
51
What is the truth about caffeine's counteractive effects?
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
What common drug does caffeine show interesting reactions to?
Nictoine
53
What are the interactions that caffeine has with nicotine?
- 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
What are the harmful effects of caffeine on reproduction?
* 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
What are the harmful effects of caffeine on the heart?
- Increased BP - Heart disease/attacks? - -> CP1A2 gene may slow metabolism - Boiled coffee may increase cholesterol
56
What are the harmful effects of caffeine to do with cancer?
* 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
What abnormal behaviour can caffeine cause?
• 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
What effects does caffeine have on bone density?
• Accelerated loss of bone density in postmenopausal women who consume less than recommended calcium dose
59
What dose of caffeine is lethal?
* Lethal dose is 30-80 cups of coffee (3-8 grams of caffeine) taken orally * Death results from respiratory collapse & convulsions
60
What can high caffeine intake cause to do with psychopathology?
• 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)
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