Download this Outline - Alcohol Medical Scholars Program

Jill Williams, MD
UMDNJ-Robert Wood Johnson Medical School
Alcohol Medical Scholars Program
Revised March 26, 2007
Assessment and Pharmacological Treatment of Tobacco Dependence
< Slide 1>
I. Introduction
A. Tobacco use is common and has many devastating effects < Slide 2>
1. ~70 million cigarette smokers in US
2. Number one preventable cause of morbidity/ mortality in US
3. > 500,000 premature deaths/year from tobacco
4. 50,000 deaths (in nonsmokers) from environmental tobacco smoke
5. Tobacco and nicotine differ - Tobacco is the harmful part of smoking, not
nicotine. It’s the smoke that kills
B. Many smokers want to quit and treatments improve outcomes < Slide 2>
1. 41% of smokers try to quit each year
2. Assessment guides treatment
3. Brief advice from a physician increases quitting
4. Treatments double success rates
C. This lecture will cover < Slide 3>
Epidemiology and consequences
Nicotine pharmacology
Assessment
Pharmacological treatments
II. Epidemiology and consequences of tobacco use < Slide 4>
A. Epidemiology
1. >1 billion tobacco users worldwide
a. ↑ in developing regions (China, India, Africa, S. America)
b. Stable or ↓ in developed nations
2. ~23% of US population smokes cigarettes < Slide 5>
a. 3% of physicians
b. 70% with mental illness or SUD ,
c. Smoking prevalence ↓ 1960s, but stable~ last 15 years
3. Tobacco forms
a. Cigarettes > 95% of all tobacco use
b. Cigar smoking
1). Non-daily use patterns
2). ~5% prevalence; increased > 50 percent since 1990s
3). ↑ in youth, women, minority groups
c. Chewing tobacco
1). Loose leaf or snuff
2) 3.5% prevalence (Men use 7x > women)
4. Prevalence ↑ in lower SES
5. Males > females; women ↑since 1950s (lung cancer deaths > breast cancer
deaths since 1987) < Slide 6>
6. Recent ↑ in youth smoking (“Pediatric epidemic”) < Slide 7>
a. Initiation during grades 6-9 (ages 11-15).
90% of all smokers start before age 18
If begin < 16, 1.6x be dependent
5 million US smokers aged 12-17 years
B. Morbidity and mortality < Slide 8>
1. Half of smokers die from a tobacco-caused disease (~ 1 in 5 US deaths)
2. Cancer
a. ~90% of lung cancers from smoking
1). #1 cause of cancer deaths in US
2). 15% 5-year survival rate
b. Other types < Slide 9>
{SOURCE: 2004 Surgeon General Report on the Health Consequences of Smoking}
1). Oral cancers (lip, tongue, mouth, and larynx)
2). Esophagus, cervix, bladder, pancreas, and kidney
3. Causes ~100% COPD
2x ↑ death from stroke/ coronary heart disease
C. Other consequences
1. Costs > $100 billion annually
a. $50 billion in medical costs
b. $50 billion lost productivity
2. Primary cause of fatal house fires
III. Assessment and treatment
A. Components of tobacco smoke < Slide 10>
1. Smoke > than 4000 chemicals
a. Carbon monoxide
b. Other toxins
1). Hydrogen cyanide
2). Formaldehyde
3). Ammonia
2. Smoke > 60 carcinogens (benzene, cadmium, nitrosamines, polycyclic aromatic
hydrocarbons (PAH))
3. Environmental Tobacco Smoke (ETS) < Slide 11>
a. Smoke from cigarettes of others
b. Class1A carcinogen, same class as asbestos
c. 50,000 additional deaths/ year in non-smokers (3000 lung cancer)
Nicotine pharmacology depends on delivery route < Slide 13>
Short half-life (2 hours)
Best absorption when smoked
1). Cigarettes (smoking) “perfect” drug delivery device
2) Reaches brain in 10 sec
3). Most reinforcing form
c. Binds to nicotinic cholinergic receptors
d. Arterial levels 6-10x higher than venous
e. Metabolized to cotinine in liver
5. Nicotine researched for possible therapeutic effect < Slide 15>
a. Ulcerative colitis
b. Alzheimer's disease
c. Parkinson's disease
d. Tourette's syndrome
e. Attention deficit disorder
f. Schizophrenia
6. Nicotine safety < Slide 16>
a. Not a carcinogen
b. Not a risk factor for cardiovascular events, even in people with
cardiovascular disease , ,
c. Risk-benefit ratio supports of using nicotine products over using
tobacco
d. Smokers misinformed re: safety/efficacy of nicotine
B. Assessment guides treatment
1. DSM IV criteria < Slide 18>
a. Nicotine dependence
1). DSM not list abuse: Clinically significant psychosocial
problems rare
2). ≥ 90% smokers meet dependence criteria
3). 3 or more of 7 DSM dependence criteria
a). Persistent desire or unsuccessful efforts to cut down or
control use
b) Activities given up or reduced
c). Use despite a physical or psychological problem
d). Tolerance
e). Withdrawal
b. Nicotine withdrawal < Slide 19>
1) Symptoms
a). Dysphoric or depressed mood
b). Insomnia
c). Irritability, frustration or anger
d). Anxiety
e). Difficulty concentrating
f). Restlessness
g). Decreased heart rate
h). Increased appetite or weight gain
2). Duration
a). Most severe 1-3 days after quitting
b). Can last 4 weeks
2. Heaviness of smoking index = measure dependence severity < Slide 20>
a. Number of cigarettes per day (cpd) smoked
b. Time to first cigarette (TTFC)
1). Smokers awaken in nicotine withdrawal
2). Smoking ≤ 30 minutes of awakening = moderate dependence
3). Smoking ≤ 5 minutes of awakening = severe dependence
C. Motivation to quit < Slide 21>
1. 70% of smokers want to quit
2. Few quit successfully without treatment
a. 33% of self-quitters remain abstinent for 2 days
b. < 5% successful
D. Provider’s role in treatment < Slide 22>
{SOURCE: PHS Guidelines, Treating Tobacco Use and Dependence: Clinical Practice Guidelines,
US Dept Health and Human services}
Use 5As for primary care settings (ask, advise, assess, assist, and arrange)
a. Ask—identify all tobacco users at every visit
b. Advise—urge users to quit
c. Assess—determine willingness to quit
d. Assist—aid in quitting
e. Arrange—follow-up
Brief physician advice ↑ quitting
More physician counseling is better
a. 10% quit rates with < 3 minutes
b. 20% quit rates >10 minutes
E. Treatments ↑ long-term abstinence
Tobacco dependence = chronic condition
a. < 25% quit successfully on their first attempt
b. Usually 8 quit attempts before successful
2. Pharmacotherapy a first line treatment
a. Doubles success
b. Recommended for all who try to quit, unless contraindications
c. Works even without psychosocial treatments
d. Best outcomes: meds + psychosocial
IV. Rationale for pharmacotherapy < Slide 24>
A. ↓ or eliminate withdrawal
B. ↓ reinforcement by nicotine ,
C. ↓ weight gain when quitting
D. Unlearn smoking behaviors
E. Manage negative mood
F. Cost-effective ,
1. Treatment cost per smoker $165 17
2. More cost-effective than mammography, anti-HTN drugs
V. First-line/ FDA approved pharmacological treatments
A. Poor absorption from nicotine replacement medication (NRT), < Slide 26>
1. Nicotine absorption is pH dependent
2. Lower dose delivered
3. Less reinforcing than smoking
4. Poorly absorbed orally
5. Poor compliance and under dosing common
6. Relative contraindications to NRT 11 < Slide 27>
a. Few unable to take nicotine
b. With caution in selected populations
1). Recent MI
2). Uses < 10 cigarettes per day
3). Pregnant/breastfeeding
4). Adolescents (Not FDA approved)
Side effects NRT
a. Usually mild
b. Local irritant at site of use
c. Systemic side effects less common
1).Dizziness
2). Nausea
3). Headache
8. Start NRT on the quit date (QD)
B. Nicotine patch
< Slide 28>
Slow onset of action
30 min to onset
6 h to peak
Continuous delivery
24 or 16 hour dosing
Night wearing relieves morning craving but disturbs sleep
Given with gradual taper
Passive dosing
Easy to use
Best compliance44
No response to acute craving
Side effects
Skin
1). Itching, tingling at patch site
2). True rash rare
Sleep disturbance, abnormal dreaming
Availability and cost
OTC
$50 for 2 week supply
Nicotine gum < Slide 29>
Buccal absorption
20-30 min onset of action
Reduced with acidic beverages (soda, coffee)
Bite and park method improves absorption and reduces side effects
Side effects
Mild- peppery taste
Throat irritation
Dyspepsia
Jaw soreness
Dosing
1 piece an hour
↑ for cravings (up to 24 pieces/ day)
6 weeks than taper
Longer more helpful
Dose: 2mg < 25 cpd; 4 mg> 25 cpd
Limitations
TMJ
Dental problems, edentulous
Availability and cost
OTC
$50 for 2 week supply
Generics available ($25-$35)
Nicotine lozenge < Slide 30>
Buccal absorption (similar to gum, more discreet)
Reduced with acidic beverages
Dissolve; don’t chew (15 min)
Side effects
Mild
Throat irritation
Dosing
1 piece an hour, ↑ for cravings
Max 20 per day
6 weeks than taper
Dose based on TTFC instead of number of cpd
Dose: 2mg if > 30 mins TTFC ; 4 mg< 30 mins TTFC
Availability and cost
OTC
$80 for 2 week supply
No generics
Limitations: none
Nicotine inhaler < Slide 31>
Buccal absorption
Oral puffer; inhaler misnomer
Reduced with acidic beverages
Hand to mouth activity helpful for some
Side effects
Mild
Throat irritation
Cough
Dosing
6-16 cartridges per day
Puff for 20 min
Limitations - frequent and continuous puffing (80 puffs =1 cigarette)
Availability and cost
a. Prescription
b. Packaged #42 or #168 cartridges (approx $1/cartridge)
c. Not covered by all insurance
Nicotine nasal spray < Slide 32>
Rapid delivery though nasal mucosa
Onset in minutes
Modest peak in 10 minutes
Side effects
Moderate- can lead to discontinuation
Sneezing
Runny nose, watery eyes
Burning in nasal mucosa
Risk for bronchospasm (h/o asthma)
Tachyphylaxis- remit with continued use
Dosing
One spray each nostril = 1 dose (2 sprays)
Minimum 8 doses/day
1-2 doses/ hr
40 doses/ day max
Limitations
Side effects
High early discontinuation
Dependence in 30% + using >6 months ,
Availability and cost
a. Prescription
b. Packaged as 4 -10mL bottles
c. Cost: $5/day; $45/ bottle
d. Not covered by all insurance
Bupropion < Slide 33>
Pharmacology
Zyban SR= Wellbutrin SR
Accidental discovery as smoking aid
Activating, non-sedating antidepressant
Effects on DA and NE
Effects as nicotinic receptor antagonist ,
Side effects
Mild to moderate
Headache
Anxiety, agitation
Dry mouth
Insomnia
Dosing
150 mg x 3-7 days, then ↑ up to 300mg daily
Start 2 weeks before quit date
7-12 weeks maintenance up to 6 months
300 mg dose associated with least weight gain (1-2 lbs at 6 mos)
Limitations/ contraindications
Seizure
Eating disorder
Current use of Wellbutrin or MAO inhibitors
Availability and cost
Prescription
Reimbursable as Wellbutrin, often not as Zyban
Cost $3 per day
Efficacy < Slide 34>
Nicotine replacement
Doubles the likelihood of success in stopping smoking as compared with placebo or no NRT 23
Meta-analysis of 110 randomized trials, 35,000 patients. Odds ratio of 6 months abstinence
compared to placebo 25
1). Overall 1.74
2). Gum 1.66
3). Patch 1.74
4). Inhaler 2.08
5). Nasal spray 2.27
6). Lozenge 2.08
Success rates 25-30% at 12 weeks
No differences in outcomes in a randomized trial of 4 types of NRT (gum= patch= nasal spray=
inhaler)
Bupropion
Efficacy comparable to NRT or ? slightly higher
Efficacy independent of antidepressant properties ,
Patient preference, cost, tolerability
Combination therapy may improve outcomes
Nicotine combinations
1). Sustained plus immediate acting for craving relief
2). Improves abstinence outcomes
3). Greater withdrawal relief
Nicotine plus bupropion
1). No medication interactions/ precautions
2). Commonly given clinically
3). Efficacy unknown, not well studied
Varenicline < Slide 35>
Partial nicotine agonist
Eliminate reward from smoking
Prevent withdrawal symptoms
Not addicting
2. 1mg BID dose superior to placebo or bupropion in 12 week trials,
3. Additional 12 weeks prevented relapse in continuation study
4. Most common side effects
a. Nausea
b. Headache
c. Insomnia
d. Abnormal dreams
VI. Conclusions < Slide 36>
1. All practitioners should treat tobacco
2. Pharmacotherapy doubles the success rates in making a quit attempt and should be
used in all smokers trying to quit
3. Six FDA approved treatments are effective and well tolerated
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