pharmacotherapy in smoking cessation

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


CDC: Health Effects of Cigarette Smoking


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


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



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?


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) =


Pretty Flower…

Scientific classification of nicotine: Kingdom: Plantae Division: Magnoliophyta Class: Magnoliopsida Order: Solanales Family: Solanaceae Genus: Nicotine Species: Nicotiana tabacum


What is in that cigarette…


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


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.


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


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!!


Withdrawal Symptoms..

Most symptoms peak 24–48 hr after quitting and subside within 2–4 weeks.


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


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.


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


Pharmacologic Methods Second-Line Therapies..

Clonidine

Nortriptyline


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)


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


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.


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


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


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.


"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)


"Nicotine gum is not gum“..


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


Nicotine Lozenges..

Dosage is based on the “time to first cigarette” (TTFC) as an indicator of nicotine addiction


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


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.


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



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)



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.


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



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



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.


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


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


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.


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)


BUPROPION SR Zyban (GlaxoSmithKline); generic

Non nicotine cessation aid Sustained-release Antidepressant Oral formulation Pregnancy Category C


BUPROPION SR

Clinical effects

craving for cigarettes

symptoms of nicotine withdrawal


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)


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


Bupropion Side Effects

Common: Insomnia (avoid bedtime dosing) Dry mouth

Less common: Tremor Skin rash


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.


VARENICLINE Chantix (Pfizer)

Nonnicotine cessation aid

Partial nicotinic receptor agonist

Oral formulation

Pregnancy Category C


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


Clinical Efficacy

JAMA 2006 Jul 5;296(1):47


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


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


Varenicline Side Effects

Common side effects: Nausea (30%) Sleep disturbance (insomnia 18%;

abnormal dreams 13%) Constipation (8%) Flatulence (6%) Vomiting (5%)


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


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.


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


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


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.


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


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


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



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



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


Arrange follow-up careARRANGE


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

pharmacotherapy in smoking cessation

Documents

pipe smoking

risk of smoking

smoking cessationshisha

smoking cessationcdc

smoking cessationwhat

smoking cessationdeadly

smoking cessationtobacco

saudi arabia