Nicotine (Final Exam) Flashcards
What is the psychoactive ingredient in tobacco (natural source)?
Nicotine
Why were cigarettes the dominate form of tobacco consumption in the 20th century?
It was due to new curing methods and invention of cigarette machine
What percentage of US adults use some tobacco product?
About 20%
What are the three routes of nicotine administration?
Smoking/Vaping, By mouth, By nose
What is the quickest way to get nicotine into your system? Why?
Smoking because it is absorbed via the lungs
What are the names of the methods for oral administration of nicotine?
chew, dip, snus
What is the name of the method for nasal administration of nicotine?
snuff
True or False: E-cigarettes are safer than cigarettes
False! There are harmful additives in the E-cigarette cartirages
Smoking/Vaping causes nicotine to hit brain very fast. How quickly does nicotine get to the brain?
7 seconds
Which is a faster route of administration: smoking or IV?
Smoking
Nicotine is mostly metabolized into ______ by a cytochrome P450 enzyme
Cotinine
Individual variation in the expression of this cytochrome P450 enzyme (metabolizes nicotine):
- Half-life of nicotine averages at 2 hours, but varies among individuals
-People with reduced nicotine metabolism are less likely to become smokers
nicotine is a (agonist or antagonist) at nicotinic acetylcholine receptors (nAChRs)
agonist
nicotine is an agonist at nicotinic acetylcholine receptors (nAChRs), which are ionotropic receptors found in the…?
-Brain and spinal cord
-autonomic nervous system
- neuromuscular junction
Acetylcholine is implicated in cortical function related to what 2 things? (ref. nicotine effects on cognition)
sustained attention and memory
True or False: Nicotine can enhance performance of attention demanding tasks
True
What type of animal showed enhanced performance on cognitive tasks with nicotine?
Rat
What does smoking do for mood according to smokers?
relaxes them, alleviates stress, and helps concentration
The mood effects reported by smokers are hypothesized to be partially associated with relief from what?
Withdrawal
What causes a high dose of nicotine to produce unpleasant symtpoms?
Largely due to autonomic actions of nicotine, but strong tolerance to these actions
Lethal doses of nicotine are rare, but what is the mechanism of death of nicotine?
It kills through depolarization block of muscles involved in respiration (similar to nerve gas)
Are withdrawal symptoms of nicotine the same or opposite to acute drug effects?
Opposite
What do regular smokers feel when they don’t smoke?
irritability, stress, and difficulty concentrating
What is acute tolerance of nicotine due to?
Desensitization of nicotinic receptors (nAChR)
Chronic tolerance lasts a long or short time after smoking cessation?
a long time
Pharmacodynamic tolerance of nicotine:
nAChRs have decreased funciton
Harmful effects of chronic use of nicotine:
- premature death
-increased risk for lung disease, cardiovascular diseases, and cognitive deficits
What is the precursor of Acetylcholine?
Choline (vitamin found in many foods)
What enzyme synthesizes Acetylcholine?
Choline acetyl-transferase (ChAT)
What happens during the degredation of ACh?
acetylcholinesterase (AChE) metabolizes ACh into choline and acetic acid
What is the vesicular transporter of ACh called?
vesicular acetylcholine transporter (VAChT)
How is ACh inactivated?
First by Metabolism and THEN Uptake
Inactivation of ACh process:
ACh undergoes rapid degradation/metabolism by AChE, converting it back to choline. Then, choline is then taken up by the choline transporter and is used to make more ACh
Types of receptors for ACh:
Muscarinic and Nicotinic
Are muscarinic ACh receptors (mAChRs) ionotropic or metabotropic?
Metabotropic (GPCRs)
Are nicotinic ACh receptors (nAChRs) ionotropic or metabotropic?
ionotropic (ion channels)
What makes up a Nicotinic ACh receptor?
It is a pentameric ligand-gated cation channel, so 5 subunits
Brain nAChRs:
-consist of 2 alpha subunits and 3 beta subunits OR just 5 alpha subunits
-binds to nicotine with higher affinity
Muscle nAChRs:
have 2 ACh binding sites
What type of cation channels do nicotinic ACh receptors have?
mostly Na+ in the periphery; NA+ and Ca2+ in the brain
Effect of nicotinic ACh receptors presynaptically and postsynaptically
Postsynaptically: rapid depolarization (EPSPs) that increase neuronal firing or contract muscle
Presynaptically: enhance release of neurotransmitters
Desensitization of nicotinic ACh receptors
nAChRs desensitize with continuous exposure to agonist (the channel closes); this is reversible. Causes acute tolerance to nicotine
Is nicotine self-administered by animals?
yes
Nicotine (increases /decreases) firing activity of DA cells in VTA. Does this cause more or less DA release at terminals in the nucleus accumbens?
increases; more
What are the nAChr subtypes?
alpha4Beta2 and alpha7
what are the different effects of the nAChR subtypes alpha4Beta2 and alpha7?
alpha4Beta2: contains receptors involved in rewarding effects of nicotine
alpha7: contains receptors involved in cognitive (attention) effects of nicotine
What route of administration leads to occupancy of alpha4Beta2 nAChRs?
smoking
The knockout of which nAChR subunit does not impair the desire to self-administer nicotine intravenously?
the knockout of alpha7
(alpha4, alpha6, and Beta2 all impaired self administration)
alpha7-containing receptors are important for nicotine effects on ________.
attention
Menthol effects on nicotine:
- menthol intensified nicotine withdrawal symptoms
-menthol increased alpha4Beta2 nAChRs (even without nicotine)
What two factors contribute to nicotine addiciton?
Psychological (cue-induced craving) and pharmacological (dependence)
NRT helps treat dependence and withdrawal. What does NRT stand for?
Nicotine Replacement Therapy
What treatment options target withdrawal AND craving?
-Buproprion (weak nAChR antagonist)
- Varenicline (partial agonist at alpha4/Beta2 receptors & is the most effective treatment)
