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Table 91-3

Cognitive and Behavioral Strategies for Tobacco Cessation

Cognitive Strategies

Focus on retraining the way a patient thinks. Often, patients will deliberate on the fact that they are thinking

about a cigarette, and this leads to relapse. Patients must recognize that thinking about a cigarette does not mean

they need to have one.

Review commitment to

quit

Each morning, say, “I am proud that I made it through another day without

tobacco!” Remind oneself that cravings and temptations are temporary and will

pass. Announce, either silently or aloud, “I am a nonsmoker, and the temptation will

pass.”

Distractive thinking Deliberate, immediate refocusing of thinking toward other thoughts when cued by

thoughts about tobacco use.

Positive self-talks, “pep

talks”

Say “I can do this” and remind oneself of previous difficult situations in which

tobacco use was avoided.

Relaxation through

imagery

Center mind toward positive, relaxing thoughts.

Mental rehearsal,

visualization

Preparing for situations that might arise by envisioning how best to handle them. For

example, envision what would happen if offered a cigarette by a friend—mentally

craft and rehearse a response, and perhaps even practice it by saying it aloud.

Behavioral Strategies

Involve specific actions to reduce risk for relapse. These strategies should be considered prior to quitting, after

determining patient-specific triggers and routines or situations associated with tobacco use. Below are strategies

for several of the common cues or causes for relapse.

Stress Anticipate upcoming challenges at work, at school, or in personal life. Develop a

substitute plan for tobacco use during times of stress (e.g., use deep breathing, take

a break or leave the situation, call a supportive friend or family member, or use

nicotine replacement therapy to manage situational cravings).

Alcohol Drinking alcohol can lead to relapse. Consider limiting or abstaining from alcohol

during the early stages of quitting.

Other tobacco users Quitting is more difficult when around other tobacco users. This is especially

difficult if there is another tobacco user in the household. During the early stages of

quitting, limit prolonged contact with individuals who are using tobacco. Ask

coworkers, friends, and housemates not to smoke or use tobacco in your presence.

Oral gratification needs Have nontobacco oralsubstitutes (e.g., gum, sugarless candy, straws, toothpicks, lip

balm, toothbrush, nicotine replacement therapy, bottled water) readily available.

Automatic smoking

routines

Anticipate routines that are associated with tobacco use and develop an alternative

plan.

Examples:

Morning coffee: change morning routine, drink tea instead of coffee, take shower

before drinking coffee, take a brisk walk shortly after awakening.

While driving: remove all tobacco from car, have car interior detailed, listen to an

audio book or talk radio, use oralsubstitutes.

While on the phone:stand while talking, limit call duration, change phone location,

keep hands occupied by doodling or sketching.

After meals: get up and immediately do dishes or take a brisk walk after eating, call

supportive friend.

Postcessation weight gain Do not attempt to modify multiple behaviors at one time. If weight gain is a barrier

to quitting, engage in regular physical activity and adhere to a healthful diet (as

opposed to strict dieting). Carefully plan and prepare meals, increase fruit and water

intake to create a feeling of fullness, and chew sugarless gum or eat sugarless

candies. Consider use of pharmacotherapy shown to delay weight gain (e.g.,

nicotine gum, lozenge, or sustained-release bupropion). Cravings for tobacco Cravings for tobacco are temporary and usually pass within 5–10 minutes. Handle

cravings through distractive thinking, take a break, do something else, take deep

breaths.

Reprinted with permission from Rx for Change: Clinician-Assisted Tobacco Cessation. Copyright 1999–2017. The

Regents of the University of California. All rights reserved.

FIRST-LINE AGENTS

Nicotine Replacement Therapy

NRT improves cessation rates by reducing the physical withdrawal symptoms

associated with tobacco cessation whereas the patient focuses on behavior

modification and coping with the psychological aspects of quitting. In addition,

because the onset of action for NRT is not as rapid as that of nicotine obtained

through smoking, patients become less accustomed to the nearly immediate,

reinforcing effects of inhaled nicotine. A meta-analysis found that all NRT

formulations result in statistically significant improvements in abstinence rates when

compared with placebo. Patients using NRT are 1.6 times as likely to quit smoking

than are those receiving placebo.

36 Figure 91-3 depicts the concentration–time curves

for the various NRT formulations, compared with a cigarette and snuff, a smokeless

form of tobacco.

37–39 Nicotine nasal spray reaches its peak concentration most

rapidly. The nicotine gum, lozenge, and oral inhaler have similar concentration

curves, and the nicotine transdermal patch has the slowest onset, but offers more

consistent blood levels of nicotine for a sustained period. Although ideally tobacco

use stops when NRT is initiated, some patients may continue to occasionally use

tobacco products after beginning NRT. This allows patients more flexibility with

continuing to use NRT if they slip and use tobacco products, or with initiating NRT

in an effort to decrease the number of cigarettes smoked prior to complete cessation.

(the “reduce to quit” method)

34,40,41

Initiating nicotine patch prior to a quit attempt

may be more effective than applying the patch on the quit date. However, data are

conflicting, and the evidence does not support using other forms of NRT prior to the

quit date.

41

p. 1910

p. 1911

Table 91-4

Pharmacologic Product Guide: FDA-Approved Medications for Smoking

Cessation

NRT Formulations Bupropion SR

Gum Lozenge

Transdermal

Patch Nasal Spray Oral Inhaler

Product

Nicorette,

a ZONNIC

b

generic

Nicorette

Lozenge

a

;

Nicorette Mini

Lozenge

a

,

(standard and

mini),

a generic

NicoDerm CQ,

a

generic

Nicotrol NS

c Nicotrol inhaler

c Zyban,

a generic

OTC OTC OTC

(NicoDerm CQ,

generic)

Rx Rx Rx

2 and 4 mg 2 and 4 mg Rx (generic) Metered spray 10-mg cartridge 150-mg sustainedrelease tablet

Original, cinnamon,

fruit, mint

Cherry, mint 7, 14, and 21 mg

(24-hour

release)

10 mg/mL

aqueous

solution

Delivers 4 mg of

inhaled nicotine

vapor

Precautions, Warnings, and Contraindications

Recent (≤2 weeks)

myocardial

infarction

Serious underlying

arrhythmias

Serious or worsening

angina pectoris

Temporomandibular

joint disease

Pregnancy

d and

breast-feeding

Adolescents (<18

years)

Recent (≤2

weeks)

myocardial

infarction

Serious

underlying

arrhythmias

Serious or

worsening

angina

pectoris

Pregnancy

d

and breastfeeding

Adolescents

(<18 years)

Recent (≤2

weeks)

myocardial

infarction

Serious

underlying

arrhythmias

Serious or

worsening

angina

pectoris

Pregnancy

d

(Rx

formulations,

category D)

and breastfeeding

Adolescents

(<18 years)

Recent (≤2

weeks)

myocardial

infarction

Serious

underlying

arrhythmias

Serious or

worsening

angina

pectoris

Underlying

chronic

nasal

disorders

(rhinitis,

nasal

polyps,

sinusitis)

Severe

reactive

airway

disease

Pregnancy

d

(category

D) and

breastfeeding

Adolescents

(<18 years)

Recent (≤2

weeks)

myocardial

infarction

Serious

underlying

arrhythmias

Serious of

worsening

angina pectoris

Bronchospastic

disease

Pregnancy

d

(category D)

and breastfeeding

Adolescents (<18

years)

Concomitant therapwith medications ormedical conditions

known to lower

seizure threshold

Hepatic impairmentPregnancy

C) and breastfeeding

Adolescents (<18

years)

Treatment-emergenneuropsychiatric

symptoms

ContraindicationsSeizure disorder

Concomitant

bupropion (e.g.,

Wellbutrin) therapyCurrent or prior

diagnosis of bulimiaor anorexia nervosaSimultaneous abrupdiscontinuation of

alcohol or sedatives(including

benzodiazepines)

Monoamine oxidaseinhibitor therapy in

previous 14 days

p. 1911

p. 1912

First cigarette

≤30 minutes

after

waking: 4 mg

First cigarette

>30 minutes

after

waking: 2 mg

Weeks 1–6:

1 piece every

1–2 hours

Weeks 7–9:

1 piece every

2–4 hours

Weeks 10–12:

1 piece every

4–8 hours

Maximum,

24

pieces/day

Chew each

piece

slowly

Park

between

cheek and

gum when

peppery

or tingling

sensation

appears

(∼15–30

chews)

Resume

chewing

when

tingle

fades

Repeat

chew and

park steps

until most

of nicotine

is gone

(tingle

does not

return;

generally

30

minutes)

First cigarette

≤30 minutes

after waking: 4

mg

First cigarette

>30 minutes

after waking: 2

mg

Weeks 1–6:

1 lozenge every

1–2 hours

Weeks 7–9:

1 lozenge every

2–4 hours

Weeks 10–12:

1 lozenge every

4–8 hours

Maximum, 20

lozenges/day

Allow to

dissolve

slowly (20–

30 minutes

for standard;

10 minutes

for mini)

Nicotine

release may

cause a

warm,

tingling

sensation

Do not chew

or swallow

Occasionally

rotate to

different

areas of the

mouth

No food or

beverages

15 minutes

before or

during use

Duration: up to

12 weeks

>10

cigarettes/day:

21 mg/day

× 4 weeks

(generic)

× 6 weeks

(NicoDerm

CQ)

14 mg/day × 2

weeks

7 mg/day × 2

weeks

≤10

cigarettes/day:

14 mg/day × 6

weeks

7 mg/day × 2

weeks

Rotate patch

application

site daily; do

not apply a

new patch

tot he same

skin site for

at least one

week.

May wear

patch for 16

hours if

patient

experiences

sleep

disturbances

(remove at

bedtime)

Duration: 8–

10 weeks

1–2 doses/hour

(8–40

doses/day)

One dose = 2

sprays (one in

each nostril);

each spray

delivers 0.5 mg

of nicotine to

the nasal

mucosa

Maximum

–5 doses/hour

or

–40 doses/day

For best

results,

initially use

at least 8

doses/day

Do not sniff,

swallow, or

inhale

through the

nose as the

spray is

being

administered

Duration: 3–6

months

6–16

cartridges/day

Individualize

dosing; initially

use 1 cartridge

every 1–2 hours

Best effects

with

continuous

puffing for 20

minutes

Initially use at

least 6

cartridges/day

Nicotine in

cartridge is

depleted after

20 minutes of

active puffing

Inhale into back

of throat or

puff in short

breaths

Do NOT inhale

into the lungs

(like a

cigarette) but

“puff” as if

lighting a pipe

Open cartridge

retains

potency for

24 hours

No food or

beverages 15

minutes

before or

during use

Duration: 3–6

months

150 mg PO

every morning ×

3 days, then

increase to 150

mg PO BID

Do not exceed

300 mg/day

Begin therapy

1–2 weeks

before quit

date

Allow at least

8 hours

between

doses

Avoid bedtime

dosing to

minimize

insomnia

Dose tapering

is not

necessary

Duration: 7–12

weeks, with

maintenance

up to 6

months in

selected

patients

Days 1–3:

0.5 mg PO evemorning

Days 4–7:

0.5 mg PO BIDWeeks 2–12:

1 mg PO BID

Begin theraweek

quit date.

Take dose eating and

with a full

glass of waDose tapernot necessaDosing

adjustment recommendfor patientswith severerenal

impairmentDuration: 12weeks; an

additional 1week coursmay be usein selected

patients

May initiateto 35 days

before targquit date ORmay reducesmoking ova 12-week

period of

treatment

prior to

quitting andcontinue

treatment fan additiona12 weeks.

Park in

different

areas of

mouth

No food or

beverages

15

minutes

before or

during use

Duration: up

to 12

weeks

p. 1912

p. 1913

Adverse Effects

Mouth or jaw soreness

Hiccups

Dyspepsia

Hypersalivation

Effects associated

with incorrect

chewing technique:

Lightheadedness

Nausea or

vomiting

Throat and mouth

irritation

Nausea

Hiccups

Mouth

Irritation

Heartburn

Headache

Sore throat

dizziness

Localskin

reactions

(erythema,

pruritus,

burning)

Headache

Sleep

disturbances

(insomnia,

abnormal or

vivid

dreams);

associated

with

nocturnal

nicotine

absorption

Nasal or

throat

irritation

(hot,

peppery,

or burning

sensation)

Rhinitis

Tearing

Sneezing

Cough

Headache

Mouth or

throat

irritation

Cough

Headache

Rhinitis

Dyspepsia

Hiccups

Insomnia

Dry mouth

Nervousness or

difficulty

concentrating

Rash

Constipation

Seizures (risk is

∼0.1%)

Neuropsychiatric

symptoms (rare;

see

PRECAUTIONS)

aMarketed by GlaxoSmithKline.

bMarketed by Niconovum USA (a subsidiary of Reynolds American, Inc.).

cMarketed by Pfizer.

dThe US Clinical Practice Guideline states that pregnant smokers should be encouraged to quit without medication basedevidence of effectiveness and theoretic concerns with safety. Pregnant smokers should be offered behavioral counseling intexceed minimal advice to quit.

e

In July 2009, the FDA mandated that the prescribing information for all bupropion- and varenicline-containing products incboxed warning highlighting the risk of serious neuropsychiatric symptoms, including changes in behavior, hostility, agitation, desuicidal thoughts and behavior, and attempted suicide. Clinicians should advise patients to stop taking varenicline or bupcontact a healthcare provider immediately if they experience agitation, depressed mood, and any changes in behavior that arnicotine withdrawal, or if they experience suicidal thoughts or behavior. If treatment is stopped because of neuropsychiapatients should be monitored until the symptoms resolve.Based on results of a mandated clinical trial, the FDA removed this in December 2016.

fFor complete prescribing information, refer to the manufacturers’ package inserts.

NRT, nicotine replacement therapy; OTC, over-the-counter (nonprescription); Rx, prescription; SR, sustained-release.

Adapted with permission from Rx for Change: Clinician-Assisted Tobacco Cessation. Copyright © 1999–2017. The RUniversity of California. All rights reserved.

p. 1913

p. 1914

Sustained-release Bupropion

Sustained-release bupropion is an atypical antidepressant medication hypothesized to

promote smoking cessation by blocking the reuptake of dopamine and norepinephrine

in the central nervous system7 and possibly by acting as a nicotine receptor

antagonist.

42 These neurochemical effects are believed to modulate the dopamine

reward pathway and reduce cravings for nicotine and symptoms of withdrawal.

7 Use

of sustained-release bupropion approximately doubles the long-term abstinence rate

when compared with placebo.

7,43

Varenicline

Varenicline is a partial agonist that binds with high affinity and selectivity at α4β2

neuronal nicotinic acetylcholine receptors.

44 The efficacy of varenicline in smoking

cessation is believed to be the result of sustained, low-level agonist activity at the

receptor site combined with competitive inhibition of nicotine binding. The partial

agonist activity induces modest receptor stimulation, leading to increased dopamine

levels, which attenuates the symptoms of nicotine withdrawal. In addition, by

blocking the ability of nicotine to activate α4β2 nicotinic acetylcholine receptors,

varenicline inhibits the surges of dopamine release that are believed to be

responsible for the reinforcement and reward associated with smoking.

44,45 Use of

varenicline more than doubles the chances of quitting when compared to placebo.

7,46

Patients should be monitored for neuropsychiatric symptoms, including changes in

behavior, mood, or suicidal thoughts and behavior.

47

SECOND-LINE AGENTS

Although not FDA-approved specifically for smoking cessation, the prescription

medications clonidine and nortriptyline are recommended as second-line agents.

7

Lack of an FDA-approved indication for smoking cessation and less desirable sideeffect profiles currently prohibit these agents from achieving first-line classification.

7

PHARMACOTHERAPY FOR TREATING

TOBACCO USE AND DEPENDENCE

Transdermal Nicotine Patch

CASE 91-1

QUESTION 1: T.B. is a 32-year-old woman who is enrolled in a worksite smoking-cessation program. During

the previous group session, the cessation counselor discussed the various medications for cessation. T.B. has

set her quit date for 1 week from today, and she is interested in starting the nicotine transdermal patch. She is

currently smoking 1.5 packs/day (PPD), which is a reduction from the 2 PPD she had been smoking for the

past 10 years. T.B. reports she smokes several cigarettes in succession immediately after waking in the

morning. She takes no medications and has no medical problems. Which nicotine transdermal product should

T.B. select, and how should it be used?

Figure 91-3 Plasma nicotine concentrations for various nicotine-containing products. (Reprinted with permission

from Rx for Change: Clinician-Assisted Tobacco Cessation. Copyright © 1999–2017. The Regents of the

University of California. All rights reserved. Plasma nicotine concentration curves derived from ChoiJH et al.

Pharmacokinetics of a nicotine polacrilex lozenge. Nicotine Tob Res. 2003;5(5):635; Schneider NG et al. The

nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet.

2001;40(9):661; and Fant RV et al. Pharmacokinetics and pharmacodynamics of moist snuff in humans. Tob

Control. 1999;8(4):387.)

p. 1914

p. 1915

Transdermal nicotine delivery systems consist of an impermeable surface layer, a

nicotine reservoir, an adhesive layer, and a removable protective liner. Although the

transdermal delivery technology varies by manufacturer, nicotine is well absorbed,

with 68% to 82% of the dose released from 24-hour patch formulations systemically

bioavailable across the skin. Plasma nicotine concentrations from the patch rise

slowly during 1 to 4 hours and peak within 3 to 12 hours after application.

14 Levels

of nicotine achieved with the transdermal patch are lower and fluctuate less than do

those achieved with tobacco products or other NRT formulations (Fig. 91-3).

The transdermal nicotine patch exhibits significantly improved abstinence rates

relative to placebo.

7,35 A meta-analysis of 25 randomized, controlled trials found

treatment with the nicotine patch (6–14 weeks) approximately doubled the likelihood

of long-term abstinence compared with placebo.

7

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