Sweatman - Smoking Cessation Flashcards
1
Q
What drugs are labeled for smoking cessation?
A
- Bupropion (Wellbutrin)
- Nicotine
- Varenicline
2
Q
What drugs are used off-label for smoking cessation?
A
- Clonidine
- Mecamylamine
- Naltrexone
3
Q
Nicotine withdrawal
A
- Nicotine: potent psychoactive drug that causes physical dependence and tolerance
- Gains access to CNS after uptake in the alveoli
- Intent of tx is to avoid the withdrawal symptoms listed in the attached chart
4
Q
Interventions to promote tobacco use cessation
A
- Quit/avoid second-hand smoke
- Assess pt willingness to attempt to quit: try to move pts along 1 stage if ready to quit
1. Pre-contemplation, contemplation, prep, action, maintenance, relapse (stages of change) - Establish quit date
- Provide self-help materials
- Offer nicotine replacement tx and o/non-nicotine meds
- Recommend a smoking cessation program -> combo of meds and program shown to be more effective
- Underlined things show the greatest potential benefit
5
Q
Tobacco-related mortality
A
- 3x higher mortality for smokers
- 1/5 deaths in the US every year -> leading cause of preventable death in the US
1. Affects smoker and second-hand - Life expectancy at least 10 years shorter than for non-smokers
- Quitting before 40 reduces risk of dying from smoking-related disease by about 90%
6
Q
Nicotine concentrations
A
- Rapid increases in nicotine
- Sustained delivery by non-cigarette products
-
Rapid INC in nicotine in brain is essential in triggering the physiological changes associated w/addiction
1. Speed of decline dictates time of onset and severity of nicotine withdrawal symptoms
7
Q
Nicotinic acetlycholine receptor
A
- Pentameric transmembrane-spanning ion channels
- PARA nicotinic receptors
- Different structural conformations involving association of different subunits, alpha and beta
8
Q
Nicotinic receptor structural diversity
A
- Various assemblies of nicotinic acetylcholine receptor subtypes broadly distributed in the brain
- Focus on ventral tegmental area, which contains alpha-7 and alpha-4, beta-2 nicotinic receptor confirmations
9
Q
Ventral tegmental area
A
-
Acute stage (a): activation of GABA (or dopamine) by nicotine = reward via tegmental pedunculopontine nucleus (TPP) -> might involve nAChR’s w/alpha-7 or beta-2
1. Blocking alpha-7 blocks rewarding effects
2. Blocking beta-2 blocks rewarding & aversive - Repeated exposure (b): GABA system desensitized, so shift to DA (mediated in part by INC glutamatergic input) -> dysregulated, so cravings and withdrawal
- VTA implicated in rewarding motivational effects of a # of addictive drugs, incl. cocaine, alcohol, and opiates
10
Q
Addictive drugs
A
- Work in modulating dopamine levels by one of a # of processes, incl. ion modulation (like w/nicotine)
1. Dopamine levels responsible for dependence and addiction with nicotine -> activity in the VTA initiates these effects - Also via activation of G-protein coupled receptors and modulation of amine transporter processes (3 mechs)
- Nicotine is highly addictive (on par w/opiates), less so than cocaine, but more than alc or benzodiazepines
11
Q
Varenicline (Chantix)
A
- Partial agonist: alpha-4, beta-2 nicotinic Ach receptor
1. Blocks effect of add’l nicotine challenge while causing release of mesolimbic dopamine - CT’s show Varenicline is most effective single drug
- Most common AE: mild, self-limiting nausea
- Depression, suicidal ideation, and emo lability have been reported -> monitor pts for behavior/mood changes (withdrawal can also cause depression)
- CV-related death and nonfatal MI and stroke more freq in pts using Varenicline than placebo
12
Q
Bupropion (Wellbutrin SR)
A
- NE and dopamine reuptake inhibitor
1. DEC cravings and withdrawal symptoms, while interacting w/pathways underlying addiction
2. Thought to DEC depressive symptoms of nicotine withdrawal b/c nicotine itself can cause anti-depressant effects that Bup helps maintain - CT’s indicate Bupropion is better than nicotine replacement, but less effective than Varenicline
- AE’s: insomnia, dry mouth, nausea
- Neuropsych effects, incl. INC risk of suicidal ideation in pts with/w/o pre-existing psych disorders
1. Monitor for adversity after and during therapy
13
Q
What two drugs are the best interventions for smoking cessation?
A
- Varenicline
- Bupropion
- Both better than nicotine replacement
- Both are associated with adverse psych effects, so pts need to be monitored during and following tx
14
Q
Clonidine
A
- Oral dosing or patch delivery (oral anti-HTN drug)
- Blocks cravings, anxiety, restlessness, tension and hunger
- AE’s: sedation, dry mouth, dizziness
- Potential utility for anxious, agitated ex-smokers who are likely to benefit from sedative side effects
15
Q
Mecamylamine
A
- Nicotine antagonist (ganglionic blocker)
- 2 small studies: nicotine + mecamylamine may be better than nicotine alone in promoting smoking cessation
- Can moderate smoking cue-induced emo response in smokers
- Contraindicated in: coronary or renal insufficiency, glaucoma, uremia
- Common AE’s: orthostatic hypotension, fatigue, sedation, constipation, N/V, dry mouth (typical signs of drug-induced autonomic dysfunction/imbalance)
17
Q
NRT
A
- Nicotine replacement therapy: alternative delivery prevents withdrawal symptoms
- Levels high enough to prevent withdrawal, but not high or rapid enough to produce dependence
- Gradually taper off consumption
-
5 forms: gum, transdermal skin patch, oral lozenge sold w/o prescription; nicotine nasal spray and oral vapor are prescription-only
1. Patch produces most constant nicotine level in the blood -> image: note that gum and patches both fulfill criteria of slower accumulation to lower overall levels, and more gradual decline, avoiding impulse to seek another nicotine “hit”
22
Q
E-cig
A
- Uses heated element to vaporize a nicotine solution for immediate inhalation
- Don’t deliver same amt of nicotine delivered by a cig (about 1/3rd or 1/4th the amount)
1. Significant acute DEC in cigarette use not sustained over 6 months (no lg CT yet) - Fewer AE’s and higher adherence than w/patches
1. Concerns about: acute poisoning, esp in peds and adolescent pops w/concurrent use of other nicotine products - Current proposal (by FDA) to bring these products under regulatory control
