Nicotine; Caffeine Flashcards
Plant of nicotine
Produced in plants of the nightshade family: insecticide properties
Nicotiana tabacum is most commonly cultivated
Juul and modern vaporizers
Nicotine salts (protonated nicotine) Earlier nicotine peak Tremendously potent
Tobacco use/exposure: Increased rates of cancer due to
nitrosamines in tobacco smoke
Tobacco use/exposure: Increased rates of
cancer, cardiovascular disease (CVD), pulmonary disease (Emphysema), pregnancy complications
Tobacco use/exposure: Teratogen
Increased pregnancy complications: malformation of embryo
First, second, third hand smoke
First - smoking
Second - through air
Third hand (smoke adhered to objects)
All convey risks
History of tobacco use
Mayans, incas, Toltecs, aztecs - religious purposes
First introduced to europe in 15th century. Mid 16th century = widespread
An important trade crop
Questions about safety date to early 17th century
The early 20th century saw researchers focus on adverse effects
Absorption of nicotine
Absorbed via mouth, nose, throat, lungs
Inhalation = most effective for nicotine delivery - exception: e-cigs
Peak absorption: 5-7 min for cigarettes (lungs)
20-30 Min for most other products
Biotransformation and elimination of nicotine
Blood brain barrier
Nicotine readily crosses blood-brain barrier
Biotransformation and elimination of nicotine
Metabolization
In liver
Active metabolite: cotinine
Mentholation slows metabolism (menthols)
Polymorphisms can affect rate of metabolism
Slower metabolizers are more likely to be light smokers
Half life nicotine
Half-life of nicotine: 2 hours (Less for chronic smokers)
Cotinine: 17 hours
Eliminated via urine
Nicotine agonist or antagonist?
Nicotine is a cholinergic agonist (increases the function of receptor)
What receptor does nicotine bind to?
nicotinic receptors = nAChRs acetylcholine receptors
Ionotropic receptors
When nicotine binds to acetylcholine receptors it creates an excitatory or inhibitory post synaptic potential?
EPSP
Nicotinic receptor desensitization
Desensitized state - Functional antagonism: high binding affinity - stays for a long time. Channel closes, molecule stays = blocks it in the long term. Becomes an antagonist.
Upregulation (acute tolerance) - first cigarette of the day feels better than second
Distribution of nicotinic receptors (AChRs)
Peripheral nervous system
Neuromuscular junction
Ganglia of autonomic nervous system
Distribution of nicotinic (AChRs) receptors
Central nervous system
Hippocampus and cerebral cortex
Basal ganglia
Ventral tegmental area (projecting to) nucleus accumbens (and other areas)
Rewarding (addictive) properties of nicotine
Indirect dopamine release
Nicotine receptors activated in the VTA or NA increase dopamine release in NA
Other constituents of tobacco enhance effects
Pharmacological effects
Wide ranging Sympathomimetic effects \+ Movement stability Cognitive enhancer (stroop test, memory test) Acute tolerance Hunger decreases
Habitual versus naive users
Naive users report negative subjective effects
Habitual users report positive subjective effects
+ build tolerance to negative subjective effects
Chippers
“social smokers” - common
Habitual users but unlikely to be addicted due to resistance to addictive effects of nicotine
Resistance bc of: genetic and environmental/social mechanisms
Why do people smoke?
Social pressures
Most chronic users will become addicted
Hard to quit
How do people quit?
Magic timeframe: 2 weeks - more about withdrawal
“Cold turkey” or with
- Nicotine replacement therapy
- nAChR agonists (Varenicline)
- Antidepressants (Bupropion, NDRI and nAChR antagonist)
Gender, ethnicity, and SES in quitting
Better rates of abstinence in men, european americans, higher socioeconomic status
Nicotine quitting studies
Groups usually don’t achieve higher than 50% quitting
Caffeine - type of drug, plant
Mild psychostimulant of the xanthine family
Found in many plants
The most used drug on earth
Found in kola nuts, cocoa tree nuts, tea leaves, coffee beans
Dark vs. light roast
The longer you roast, the less caffeine.
Light roast = more caffeine
Energy drinks
75mg of caffeine plus other xanthines
Fastest growing beverage market
alcohol mixed with energy drinks - dangerous because of different half lives
Caffeine pharmacokinetics
Administration: Oral Absorption: intestines Crosses BBB -> adenosine receptors Metabolized in liver Eliminated via urine (the metabolites)
Active metabolites
theobromine, theophylline, paraxanthine
Peak concentration and half life
40min after ingestion
Half-life varies tremendously
Cigarettes and coffee
Polydrug use
Smoking increases CYP-1A2 activity (which breaks down caffeine)
Smoking increases elimination of the caffeine
Caffeine Pharmacodynamics
A1 and A2 adenosine receptor antagonists
Adenosine receptors are omnipresent throughout entire body
Caffeinism
High doses of caffeine = can lead to caffeinism
Adverse effects of caffeine >500mg - start to emerge
Sweating, high HR anxiety, agitation and insomnia.
No tolerance towards physiological effects, just acute subjective
Physiological effects of caffeine
Increased heart rate
Blood vessel constriction
Increased breathing rate
Reduced appetite
Behavioral and subjective effects
Attention Alertness \+ Positive mood Elevated sense of wellbeing
Dependence - tolerance
We build tolerance with: mood alertness, anxiousness, acute subjective effects (feeling awake)
No tolerance: cardiovascular activity, blood vessel constriction, physiological effects
Dependence - withdrawal
Just mornings
Not considered a substance of concern by the DSM5 not “addictive”
But caffeinism and withdrawal are in the DSM-5
Why do people consume caffeinated products?
Increased sense of energy/mood (go away with chronic use)
Physical dependence
Incentive sensitization - dopamine
Products with caffeine taste good
Neuroprotection
Alzheimer’s: affects cholinergic neurons early - Potential therapeutic: nAChR agonists
Nicotine and schizophrenia
smoking is disproportionately high
Why is nicotine smoking disproportionately high in people with schizophrenia?
The self-medication hypothesis: nicotine administration may be instrumental
Smoking may lessen negative symptoms, improves sensory processing, speeds antipsychotic medication metabolism (take away side effects), act as cognitive enhancer
Smoking cigarettes and neurodegeneration
Smoking cigarettes associated with increased neurodegeneration (alzheimer’s, dementia)
Nicotine and neurodegeneration
Inversely correlated with risk of Parkinson’s disease. Nicotine without smoking may be neuroprotective.
Caffeine and neuroprotection
- Caffeine + parkinson’s causing chemical protects rodent from parkinson (Similar effects for amyotrophic lateral sclerosis and alzheimer’s)
- Delays age-related cognitive decline, especially in women
- 2-3 coffee cups a day = 25% lower risk of dementia/ stroke
Caffeine and neurodegeneration
May speed up the arrival of symptoms in huntington’s disease (genetic disease)
