Sweatman - Smoking Cessation Flashcards Preview

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Flashcards in Sweatman - Smoking Cessation Deck (25):
1

What drugs are labeled for smoking cessation?

- Bupropion (Wellbutrin) 

- Nicotine

- Varenicline 

2

What drugs are used off-label for smoking cessation?

- Clonidine 

- Mecamylamine 

-Naltrexone

3

Nicotine withdrawal

- 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

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4

Interventions to promote tobacco use cessation

- 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

Tobacco-related mortality

- 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

Nicotine concentrations

- 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

Nicotinic acetlycholine receptor

- Pentameric transmembrane-spanning ion channels

- PARA nicotinic receptors 

- Different structural conformations involving association of different subunits, alpha and beta 

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8

Nicotinic receptor structural diversity

- 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

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9

Ventral tegmental area

- 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

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10

Addictive drugs

- 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

Varenicline (Chantix)

- 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

Bupropion (Wellbutrin SR)

- 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

What two drugs are the best interventions for smoking cessation?

- 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

Clonidine

- 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

Mecamylamine

- 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) 

16

Naltrexone

- Opiate antagonist 

- 8 trials (over 1200 pts): no evidence of an effect of Naltrexone alone or as adjunct to NRT on long-term smoking abstinence 

- May be useful in treating other forms of addiction 

17

NRT

- 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" 

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18

Nicotine patch

- Vary in dose and duration of delivery 

- 12-wk course w/step-down titration 

- AE's: application site rxns, headaches, cold and flu-like symptoms common

- Caution: underlying CV disease, diabetes, mod-severe hepatic impairment, peptic ulcers, pheochromo-cytoma, uncontrolled hyperthryoidism (b/c can stimulate both branches of ANS)

1. Smoking while on patches may increase risk of CV events (bc nicotine doses will be addictive)

19

Nicotine gum

- 2 mg doses; do not exceed 24 pieces/day (12-wks)

- Avoid eating/drinking 15 minutes prior to gum 

- Jaw pain/orodontal problems from chewing 

- Headache, indigestion, nausea common 

- Pts may transfer nicotine addiction from cigs to gum (esp. if more than suggested dose consumed)

20

Nicotine inhaler/spray

- Inhaler: 12-wk course 

- Spray: minimum 3-mo course 

- Localized irritation in mouth or nostrils 

- Mild symptoms: headache, nausea, heartburn, hiccoughs 

21

Which NRT has best track record?

- All produce a comparable beneficial effect 

- Largest databases exist for patches and gum, but still not as good as Varenicline

- Evidence also looks good for spray and inhaler, but not as much out there (may be the best)

22

E-cig

- 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 

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23

Potential harms of quitting?

- Nicotine withdrawal symptoms 

- Exacerbation of depression among pts w/prior hx of affective disorder 

- Altered PK's of certain psych drugs 

1. Monitor closely the actions or side effects of psych meds (OTC or prescribed) in smokers and tobacco users who are attempting to quit

2. Would be most problematic during early stages of quitting 

24

Pregnancy

- Smoking in pregnancy = growth restriction, preterm delivery, and stillbirth 

- Psych interventions should be considered as first line of treatment 

- Oral NRT can be considered for pregnant women

- Evidence for safety of other pharm smoking cessation txs during pregnancy or while breastfeeding is lacking

25

Mind-body practices

- Research suggests mind-body interventions (like meditation) have potential to help reduce smoking, and aid cessation 

- However, study design flaws, lack of adherence, and other issues hinder drawing any definitive conclusions