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Pharmacotherapy in Smoking Cessation
Burden of Smoking
Compared with nonsmokers, smoking is estimated to increase the risk of— coronary heart disease by 2 to 4 times stroke by 2 to 4 times men developing lung cancer by 23 times women developing lung cancer by 13 times dying from chronic obstructive lung
diseases by 12 to 13 times
Pharmacotherapy in Smoking Cessation
CDC: Health Effects of Cigarette Smoking
Pharmacotherapy in Smoking Cessation
Cost of Smoking..
0 10 20 30 40 50 60 70 80
Annual lost productivity
costs (1995–1999)
Medical expenditures
(1998)
Billions of dollars
Men, $55.4 billion
Ambulatory care, $27.2 billion
Prescription
drugs, $6.4
billion
Women, $26.5 billion
Nursing home,
$19.4 billion
Other care, $5.4 billion
Centers for Disease Control and Prevention. (2002). MMWR 51:300–303.
Hospital care, $17.1 billion
Societal costs: $7.18 per pack
Prevalence of Smoking among Saudi Population
Pharmacotherapy in Smoking Cessation
Current smoking among Saudi population ranges form 2.4-52.9% (median 17.5%) Male 13-38% (median=26%) Females 1-16% (Median=9%)
Risk of smoking was associated with being male, single and highly educated.
20-50% of smokers started at or before the age of 15
Common reasons for smoking: relief from psychological tension, boredom and imitating others.
Bassiony M. Smoking In Saudi Arabia. Saudi Med J 2009; 30(7): 876-881
Prevalence of Smoking among Saudi Population
Pharmacotherapy in Smoking Cessation
Pharmacotherapy in Smoking Cessation
Deadly Habit..
CigarsCigarettes Water pipe (shishah)
Bidis
Spit tobacco
Smokless tobacco:
SnuffChewing
Inhalation tobacco:
Types of Smoking
Is Shisha safer than cigarettes with less nicotine content?
Pharmacotherapy in Smoking Cessation
Shisha vs. Cigarette
A typical 1 hr session of water-pipe smoking involves inhaling 100-200x volume of smoke inhaled with one cigarette.
=
70 regular cigarettes
20 regular cigarettes
Nicotine in1 head
(Mua'sel)
Nicotine in1 head
(unflavored) =
Pharmacotherapy in Smoking Cessation
Pretty Flower…
Scientific classification of nicotine: Kingdom: Plantae Division: Magnoliophyta Class: Magnoliopsida Order: Solanales Family: Solanaceae Genus: Nicotine Species: Nicotiana tabacum
Pharmacotherapy in Smoking Cessation
What is in that cigarette…
Pharmacotherapy in Smoking Cessation
Pharmacological effects of Nicotine
Ganglionic cholinergic receptor agonist: Centrally, increases:
Increases cognitive functionPsychomotor activity sensorimotor
performanceAttention and memory
Peripherally, increases: respiratory rateHeart rateBlood pressureCoronary blood flow
Pharmacotherapy in Smoking Cessation
Pharmacological effects of Nicotine
low doses nicotine increases alertness and
cognitive functioning by stimulating the cerebral cortex.
High doses nicotine stimulates the “reward”
center in the limbic system of the brain.
Pharmacotherapy in Smoking Cessation
Tobacco Dependence..
Tobacco DependenceTobacco Dependence
Treatment should address the physiological and the behavioral
aspects of dependence.
PhysiologicalPhysiological BehavioralBehavioral
Treatment Treatment
The addiction to nicotine
Medications for cessation
The habit of using tobacco
Behavior change program
Pharmacotherapy in Smoking Cessation
Health benefits of Quitting Smoking..
Lung cilia regain normal function
Ability to clear lungs of mucus increases
Coughing, fatigue, shortness of breath decrease
Excess risk of CHD decreases to half that of a
continuing smokerRisk of stroke is reduced to that of people who have never smoked
Lung cancer death rate drops to half that of a
continuing smoker
Risk of cancer of mouth, throat, esophagus,
bladder, kidney, pancreas decrease
Risk of CHD is similar to that of people who have never smoked
2 weeks to
3 months
1 to 9 months
1year
5years
10years
after15 years
Circulation improves, walking becomes easier
Lung function increases up to 30%
If quitting is so beneficial why do people still smoke!!
Pharmacotherapy in Smoking Cessation
Withdrawal Symptoms..
Most symptoms peak 24–48 hr after quitting and subside within 2–4 weeks.
Pharmacotherapy in Smoking Cessation
Weight Gain
In a study of 5247 patients age 35 and older people who had quit smoking
former smokers were on average 4.4 kg heavier than men who continued smoking.
Women who were former smokers were on average 5.0 kg heavier than women who continued smoking.
N Eng J Med 1995; 333: 1165-1175
Pharmacotherapy in Smoking Cessation
Nearly 41% of smokers try to quit smoking each year, relapse is common, and only about 10% achieve and maintain abstinence
MMWR Morb Mortal Wkly Rep. 2004;53:427-431.
Pharmacotherapy in Smoking Cessation
Pharmacologic MethodsFirst-Line Therapies..
Three general classes of FDA-approved drugs for smoking cessation: Nicotine replacement therapy (NRT)
Nicotine gum, patch, lozenge, nasal spray, inhaler
Psychotropics Sustained-release bupropion
Partial nicotinic receptor agonist Varenicline
Pharmacotherapy in Smoking Cessation
Pharmacologic Methods Second-Line Therapies..
Clonidine
Nortriptyline
Pharmacotherapy in Smoking Cessation
NRT: PRODUCTS..
Polacrilex gum Nicorette (OTC) Generic nicotine gum (OTC)
Lozenge Commit (OTC) Generic nicotine lozenge (OTC)
Transdermal patch Nicoderm CQ (OTC) Generic nicotine patches (OTC, Rx)
Nasal spray Nicotrol NS (Rx)
Inhaler Nicotrol (Rx)
Pharmacotherapy in Smoking Cessation
PLASMA NICOTINE CONCENTRATIONS for NICOTINE-CONTAINING PRODUCTS..
0
5
10
15
20
25
1/0/1900 1/10/1900 1/20/1900 1/30/1900 2/9/1900 2/19/1900 2/29/1900
Pla
sm
a n
ico
tin
e (
mc
g/l
)
Cigarette
Moist snuff
Nasal spray
Inhaler
Lozenge (2mg)
Gum (2mg)
Patch
Pharmacotherapy in Smoking Cessation
Considerations with NRT..
Patients with underlying cardiovascular disease: Recent myocardial infarction (within past 2 weeks) Serious arrhythmias Serious or worsening angina
Patients with other underlying conditions Active temporomandibular joint disease (gum only)
Pregnancy
Lactation
NRT products may be appropriate for these patients if they are under medical supervision.
Pharmacotherapy in Smoking Cessation
Considerations with NRT..
NRT is not FDA-approved for use in children or adolescents
Nonprescription sales (patch, gum, lozenge) are restricted to adults ≥18 years of age NRT use in minors requires a
prescription Patients should stop using all forms of
tobacco upon initiation of the NRT regimen
Pharmacotherapy in Smoking Cessation
Nicotine Gum ..
Resin complex Nicotine Polacrilin
Sugar-free chewing gum base
Contains buffering agents to enhance buccal absorption of nicotine
Available: 2 mg, 4 mg; regular, FreshMint, Fruit Chill, mint, & orange flavor
Pharmacotherapy in Smoking Cessation
Nicotine Gum ..
DISADVANTAGES Gum chewing may
not be socially acceptable.
Gum is difficult to use with dentures.
Patients must use proper chewing technique to minimize adverse effects.
ADVANTAGES Gum use may
satisfy oral cravings.
Gum use may delay weight gain.
Patients can titrate therapy to manage withdrawal symptoms.
Pharmacotherapy in Smoking Cessation
"Nicotine gum is not gum“..
Dosing is based on current smoking pattern:
# of cigarettes/d recommended strength<25 cigarettes/day 2 mg> 25 cigarettes/day 4 mg
week 1-6 week 7-9 week 10-121 q 1-2 h 1 q 2-4 h 1 q 4-8 h
Recommended usage schedule:
(not to exceed 24 pieces/d)
Pharmacotherapy in Smoking Cessation
"Nicotine gum is not gum“..
Pharmacotherapy in Smoking Cessation
Nicotine Lozenges..
Nicotine polacrilex formulation Delivers ~25% more nicotine than
equivalent gum dose Sugar-free, mint or cherry flavor
(boxed or POP-PAC) Contains buffering agents to
enhance buccal absorption of nicotine
Available: 2 mg, 4 mg
Pharmacotherapy in Smoking Cessation
Nicotine Lozenges..
Dosage is based on the “time to first cigarette” (TTFC) as an indicator of nicotine addiction
Pharmacotherapy in Smoking Cessation
Nicotine Lozenges..
week 1-6 week 7-9 week 10-121 lozenges 1 lozenges 1
lozengesq 1-2 h 1 q 2-4 h 1 q 4-8 h
at least 9 Lozenges/day during the first 6 weeks
no more than 5 lozenges in 6 hrs, 20 lozenges/day
Stop using at the end of 12 weeks
Pharmacotherapy in Smoking Cessation
Nicotine Lozenges..
DISADVANTAGES
Gastrointestinal side effects (nausea, hiccups, and heartburn) may be bothersome.
ADVANTAGES Lozenge use
may satisfy oral cravings.
The lozenge is easy to use and conceal.
Patients can titrate therapy to manage withdrawal symptoms.
Pharmacotherapy in Smoking Cessation
Transdermal Nicotine Patch..
Nicotine is well absorbed across the skin
Delivery to systemic circulation avoids hepatic first-pass metabolism
Plasma nicotine levels are lower and fluctuate less than with smoking
Pharmacotherapy in Smoking Cessation
Transdermal Nicotine Patch..
Pharmacotherapy in Smoking Cessation
Transdermal Nicotine Patch..
Product Light smoker Heavy smoker
Nicotrol < 10 cig/dNot indicated
>10 cig/dStep 1 (15mg x 6 wks)Step 2 (10 mg x 2 wks)Step 3 (5 mg x 2 wks)
Nicoderm CQ
< 10 cig/dStep 2 (14 mg x 6 wks)Step 3 (7 mg x 2 wks)
>10 cig/dStep 1 (21 mg x 6 wks)Step 2 (14 mg x 2 wks)Step 3 (7 mg x 2 wks)
Generic (Habitrol)
< 10 cig/dStep 2 (14 mgx 6 wks)Step 3 (7 mg x 2 wks)
>10 cig/dStep 1 (21 mg x 6 wks)Step 2 (14 mg x 2 wks)Step 3 (7 mg x 2 wks)
Pharmacotherapy in Smoking Cessation
Transdermal Nicotine Patch..
DISADVANTAGES Patients cannot titrate the dose.
Allergic reactions to the adhesive may occur.
Should not used in patients with dermatologic conditions
ADVANTAGES The patch provides consistent nicotine levels.
The patch is easy to use and conceal.
Fewer compliance issues are associated with patch use.
Pharmacotherapy in Smoking Cessation
Nicotine Nasal Spray..
Aqueous solution of nicotine in a 10-ml spray bottle
Rapid absorption across nasal mucosa
faster onset of action:(tmax 11–13 minutes) compared to other NRT
Pharmacotherapy in Smoking Cessation
Nicotine Nasal Spray..
One dose = 1 mg nicotine (2 sprays, one 0.5 mg spray in each nostril)
Start with 1–2 doses per hour Increase prn to max 5 doses/hr or 40
mg (80 sprays; ~½ bottle) daily For best results, use at least 8 doses
daily for the first 6–8 weeks Termination: gradual tapering over
an additional 4–6 weeks
Pharmacotherapy in Smoking Cessation
Nicotine Nasal Spray..
DISADVANTAGES Nasal/throat irritation may be bothersome.
Nasal spray has higher dependence potential.
Should not use in patients with chronic nasal disorders or severe reactive airway disease.
ADVANTAGES Easy to titrate therapy to rapidly manage withdrawal symptoms.
Pharmacotherapy in Smoking Cessation
Nicotine Inhaler..
Nicotine inhalation system consists of: Mouthpiece Cartridge with porous plug
containing 10 mg nicotine Delivers 4 mg nicotine
vapor, absorbed across buccal mucosa
May satisfy hand-to-mouth ritual of smoking
Pharmacotherapy in Smoking Cessation
Nicotine Inhaler..
Start with 6 cartridges/day Increase prn to max of 16
Cartridges/day Use for min of 3 weeks, max of 12
weeks Gradual dosage reduction: if
needed over additional 6–12 weeks
Pharmacotherapy in Smoking Cessation
Nicotine Inhaler..
DISADVANTAGES Bothersome throat or mouth irritation.
Cartridges should not be stored in very warm conditions or used in very cold conditions.
Use with caution in patients with underlying bronchospastic disease.
ADVANTAGES Easy to titrate therapy to manage withdrawal symptoms.
Inhaler mimics the hand-to-mouth ritual of smoking.
Pharmacotherapy in Smoking Cessation
NRT Summary …
Compliance highest with the patch. Smoking cessation is similar with
continuous abstinence rates at 12 weeks : odds ratio for abstinence with NRT vs. control
was 1.77 (95% CI 1.66-1.88) with odds ratio: 1.66 for gum (at least 48 trials) 1.81 for patches (at least 30 trials) 2.35 for nasal spray (at least 4 trials) 2.14 for inhaled nicotine (at least 4 trials) 2.05 for nicotine sublingual tablet/lozenge (at
least 2 trials)
Pharmacotherapy in Smoking Cessation
BUPROPION SR Zyban (GlaxoSmithKline); generic
Non nicotine cessation aid Sustained-release Antidepressant Oral formulation Pregnancy Category C
Pharmacotherapy in Smoking Cessation
BUPROPION SR
Clinical effects
craving for cigarettes
symptoms of nicotine withdrawal
Pharmacotherapy in Smoking Cessation
Bupropion Contraindications:
Seizure disorder Patients taking
Wellbutrin, Wellbutrin SR, Wellbutrin XL MAO inhibitors in preceding 14 days
Current or prior diagnosis of anorexia or bulimia nervosa
Patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines)
Pharmacotherapy in Smoking Cessation
Bupropion Dosing..
Initial treatment 150 mg po q AM x 3 days
Then… 150 mg po bid Duration, 7–12 weeks
Patients should begin therapy 1 to 2 weeks PRIOR to their quit date to ensure that
therapeutic plasma levels of the drug are achieved.
If no significant progress toward abstinence by 7th
week, D/C treatment
Reevaluate and restart at later
date
Pharmacotherapy in Smoking Cessation
Bupropion Side Effects
Common: Insomnia (avoid bedtime dosing) Dry mouth
Less common: Tremor Skin rash
Pharmacotherapy in Smoking Cessation
Bupropion..
DISADVANTAGES Increased seizure risk
Several contraindications and precautions preclude use.
ADVANTAGES Convenient, an oral formulation with twice-a-day dosing.
Beneficial for patients with depression.
Pharmacotherapy in Smoking Cessation
VARENICLINE Chantix (Pfizer)
Nonnicotine cessation aid
Partial nicotinic receptor agonist
Oral formulation
Pregnancy Category C
Pharmacotherapy in Smoking Cessation
VARENICLINE
Binds with high affinity and selectivity at 42 neuronal nicotinic acetylcholine receptors
Partial agonists at nAChR stimulate the release of sufficient dopamine to reduce craving and withdrawal
simultaneously acting as a partial antagonist by blocking the binding and consequent reinforcing effects of smoked nicotine.
Clinical effects symptoms of nicotine withdrawal
Blocks dopaminergic stimulation responsible for reinforcement & reward associated with smoking
Pharmacotherapy in Smoking Cessation
Clinical Efficacy
JAMA 2006 Jul 5;296(1):47
Pharmacotherapy in Smoking Cessation
Varenicline Dosing
Patients should begin therapy 1 week PRIOR to their
quit date. The dose is gradually increased to minimize treatment-related nausea and
insomnia.Treatment Day Dose
Day 1 to day 30.5 mg qd
Day 4 to day 70.5 mg bid
Day 8 to end of treatment*1 mg bid
Initial dose titration
* Up to 12 weeks
Pharmacotherapy in Smoking Cessation
Varenicline in renal impairment
Doses should not exceed 0.5 mg twice daily in patients with substantial renal dysfunction
(creatinine clearance <30 mL/min or 0.5 mg per day) in patients on hemodialysis
Pharmacotherapy in Smoking Cessation
Varenicline Side Effects
Common side effects: Nausea (30%) Sleep disturbance (insomnia 18%;
abnormal dreams 13%) Constipation (8%) Flatulence (6%) Vomiting (5%)
Pharmacotherapy in Smoking Cessation
Varenicline
FDA advises clinicians to monitor patients due to reports of varenicline (Chantix) possibly associated with suicidal thoughts, aggressive and erratic behavior, and excessive drowsiness.
http://www.fda.gov/medwatch/safety/2008/safety08.htm#Varenicline
Pharmacotherapy in Smoking Cessation
Varenicline
DISADVANTAGES May induce nausea
in up to one third of patients.
Post-marketing surveillance data not yet available.
ADVANTAGES An oral
formulation with twice-a-day dosing.
New mechanism of action for persons who previously failed using other medications.
Pharmacotherapy in Smoking Cessation
LONG-TERM (6 month) QUIT RATES for AVAILABLE CESSATION MEDICATIONS
0
5
10
15
20
25
30
Nicotine gum Nicotinepatch
Nicotinelozenge
Nicotinenasal spray
Nicotineinhaler
Bupropion Varenicline
Active drugPlacebo
Data adapted from Silagy et al. (2004). Cochrane Database Syst Rev; Hughes et al., (2004). Cochrane Database Syst Rev.; Gonzales et al., (2006). JAMA and Jorenby et al., (2006). JAMA
Per
cen
t q
uit 19.5
14.6
11.5
8.6
16.4
8.8
23.9
11.8
17.1
9.1
20.0
10.29.3
22.4
Pharmacotherapy in Smoking Cessation
Comparative Daily Costs of Pharmacotherapy
0 2 4 6 8
Nasal spray
Patch
Varenicline
Cigarettes (1 pack/ day)
Lozenge
Bupropion SR
Gum
Inhaler $6.07
$5.81
$5.73
$5.26
$3.91
$3.67
$4.22
$4.26
Pharmacotherapy in Smoking Cessation
The RESPONSIBILITY of HEALTH PROFESSIONALS
It is inconsistent
to provide health care and
—at the same time—
remain silent (or inactive)
about a major health risk.TOBACCO CESSATION
is an important component of THERAPY.
Pharmacotherapy in Smoking Cessation
Barriers ..
Some clinicians question the effectiveness of smoking cessation pharmacotherapies
Many clinicians lack basic knowledge on how to identify smokers quickly and easily which treatments are efficacious, how such treatments can be delivered the relative efficacy of different treatment modalities.2
Clinicians may be unaware of the availability of effective treatment methods
Inadequate clinic or institutional support for routine assessment and treatment of tobacco use
Al-Doghether. Annals of Saudi Medicine, Vol 21, Nos 1-2, 2001
Pharmacotherapy in Smoking Cessation
The 5 A’s
ASK about tobacco USE
ADVISE tobacco users to QUIT
ASSESS READINESS to make a quit attempt
ASSIST with the QUIT ATTEMPT
ARRANGE FOLLOW-UP care
Pharmacotherapy in Smoking Cessation
The 5 A’s (cont’d)
Ask about tobacco use “Do you ever smoke or use any type of tobacco?”
“I take time to ask all of my patients about tobacco use—because it’s important.”
“Medication X often is used for conditions linked with or caused by smoking. Do you, or does someone in your household smoke?”
“Condition X often is caused or worsened by smoking. Do you, or does someone in your household smoke?”
ASK
Pharmacotherapy in Smoking Cessation
The 5 A’s (cont’d)
tobacco users to quit (clear, strong, personalized, sensitive) “It’s important that you quit as soon as possible,
and I can help you.”
“I realize that quitting is difficult. It is the most important thing you can do to protect your health now and in the future. I have training to help my patients quit, and when you are ready, I will work with you to design a specialized treatment plan.”
ADVISE
Pharmacotherapy in Smoking Cessation
The 5 A’s (cont’d)
Assess readiness to make a quit attemptASSESS
Assist with the quit attempt Not ready to quit: provide motivation
Ready to quit: design a treatment plan
Recently quit: relapse prevention
ASSIST
Pharmacotherapy in Smoking Cessation
Arrange follow-up careARRANGE
The 5 A’s (cont’d)
Number of sessions
Estimated quit rate*
0 to 1 12.4%
2 to 3 16.3%
4 to 8 20.9%
More than 8 24.7%* 5 months (or more) postcessation
Fiore et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS.
PROVIDE ASSISTANCE THROUGHOUT THE QUIT PROVIDE ASSISTANCE THROUGHOUT THE QUIT ATTEMPTATTEMPT