Flashcards in Smoking Cessation Deck (47)
Labeled drugs for smoking cessation?
Bupropion, Varenicline, Nicotine
What does nicotine do to the body?
It activates nicotinic acetylcholine receptors (nAchRs), which are widely distributed in the brain, and induces the release of dopamine in the nucleus accumbens.
How much is life expectancy shortened in smokers?
What demographics have the highest risk for second hand smoke?
small, black, poor children, especially in rental housing
What are some symptoms of nicotine withdrawal?
How do nicotine concentrations differ with time in cigarettes vs. chewing tobacco/snuff?
cigarettes tend to produce a more rapid effect but non-cigarette products tend to last longer
Where does nicotine bind?
pentameric transmembrane spanning ion channels (these can take on many different conformations)
What kinds of nicotinic receptor conformations are found in the ventral segmental area of the brain?
a7, and a4b2 conformations
How does nicotine affect the ventral segmental area of the brain initially?
activation by nicotine of GABA neurons in the VTA
produces rewarding effects through a GABA-dependent system that projects to the tegmental pedunculopontine nucleus (TPP)
What are these 'rewarding' effects of nicotine binding?
1) Activation of presynaptic nicotinic acetylcholine receptors (nAChRs) that contain the alpha7 subunit (as blockade of this subunit interferes with the acute rewarding effects of nicotine, but leaves the aversive signal intact)
However, nicotine might also exert its motivational effects through direct actions on nAChRs containing the beta2
subunit and located on GABA or dopamine neurons, as pharmacological blockade or genetic deletion of this subunit blocks both the aversive and rewarding effects of nicotine.
In this model, nAChRs are distributed on both VTA neuronal populations, and nicotine-induced activation of these receptors can therefore regulate the motivational effects of nicotine through either non-DA or DA systems.
How is this changed with repeated nicotine exposure?
The GABA system that signals reward becomes desensitized, leading to a net shift in the action of nicotine to the DA neurons. This shift is mediated at least partly by increased glutamatergic input to the DA system. The shift in the functional balance between GABA and DA neuronal populations in the VTA might lead to a dysregulated DA signal in the VTA, which in turn leads to the aversive psychological effects of nicotine craving and withdrawal, and/or to the potentiation of the incentive salience of nicotine and its compulsive use.
So, again, what is responsible for addiction to nicotine?
increasing dopamine levels. Activity in the VTA is directly responsible for initiating these effects.
How addictive is nicotine compared to other addictive substances?
LESS addictive than amphetamine or cocaine, but MORE addictive than alcohol or bento-diazepines. On par with opiates.
How does Varenicline (Chantix) work?
partial agonist at the a4B2 nicotinic ACh receptor (this is the most effective single drug)
AEs of Varenicline?
-most common = mild self-limiting nausea
Other risks of using Chantix?
-nonfatal MI and stroke
How does Bupropion work?
Nor and DA re-utake inhibitor
Upsides of Bupropion?
decreases craving and withdrawal symptoms
T or F. Bupropion is better than nicotine replacement but less effective than varenicline
AEs of Bupropion?
How does Clonidine work?
an oral antihypertensive drug that seems to block many of the AEs of nicotine withdrawal (craving, anxiety, hunger)
AEs of Clonidine?
-sedation, dry mouth
-rebound HTN if rapidly withdrawn
What patients is Clonidine best for?
anxious, agitated ex-smokers who are likely to benefit from sedative effects
How does Mecamylamine work?
nicotine antagonist (ganglionic blocker)
T or F. Nicotine plus Mecamylamine may be superior to nicotine alone in promoting smoking cessation
When is Mecamylamine contraindicated?
-coronary or renal insufficiency
AEs of Mecamylamine?
-constipation, dry mouth
these adverse effects are associated with drug-induced
autonomic dysfunction or imbalance.
Mecamylamine can moderate ________ in smokers
smoking cue-induced emotional response
How does Naltrexone work?
opiate antagonist (maybe not all that effective for smoking cessation)