Smoking Cessation

Smoking Cessation !! How to become a real option ???? Dr. Assem Fouad El Esssawy Lecturer of Chest Diseases Fayoum University. www.smokerclinic.com

Why people smoke / Is smoking a life style choice?
Smoking a cigarette for a beginner is a symbolic act of rebellion
Smoking is not a life style choice
Creates a dependent state
Nicotine addiction is a complex process
Quitting smoking leads to decrements in attention and cognition
Impaired concentration, thinking, and performance associated with nicotine deprivation are strong motivating factors to smoke
M.J Jarvis, BMJ 2004;328:277-279 Heishman SJ. Nicotine Tob Res. 1999;1:S144 www.smokerclinic.com

Mechanism of Action of Nicotine in the Central Nervous System
Nicotine binds preferentially to nicotinic acetylcholinergic (nACh) receptors in the central nervous system; the primary is the  4  2 nicotinic receptor in the Ventral Tegmental Area (VTA)
After nicotine binds to the  4  2 nicotinic receptor in the VTA, it results in a release of dopamine in the Nucleus Accumbens (nAcc) which is believed to be linked to reward
 4  2  2  2  4  4  2 Nicotinic Receptor

Smoking is a Chronic disease
The therapeutic approach is based on:
Motivation of patients and their willingness to quit
Reinforce the motivation of the patient to initiate smoking cessation
Ease the withdrawal period and
Prevent relapse
Success is often obtained only after several attempts
Clinicians should adopt the same attitude as they would with other chronic disorders.
www.smokerclinic.com

Efficacious approaches for smoking cessation
Two types of approaches have demonstrated their efficacy for smoking cessation:
Counseling
Pharmacotherapy
The best results are obtained by combining the two approaches
Fiore MC. Treating tobacco use and dependence. Resp Care 2000;45:1200 West R. Smoking cessation guidelines for health professionals: an update. Thorax 2000;55:987 Simon JA. Smoking cessation counseling (intensive vs minimal). Am J Med 2003;114(7):555 www.smokerclinic.com

Practical steps www.smokerclinic.com

“ 1” Ask: The smoking history
Age started smoking
Number of cigarettes smoked daily
How soon after waking does the patient smoke
Previous attempts/success/aides used
Previous withdrawal symptoms experienced
Reasons for failure
Any smokers in the home
Motivation e.g. health, finance

“ 2” Assess: measurements of smoking intensity
(Modified) Fagerstr ̈ om Test for Nicotine Dependence
Biochemical - serum, urine or salivary cotinine - exhaled carbon monoxide
www.smokerclinic.com CO measure is useful for reinforcing patient’s motivation to quit

Modified Fagerstrom 1991 www.smokerclinic.com

Preparing the quitting day
A personalized action plain must be
prepared in association with the patient
Potential causes to relapse and how to
cope with them
A smoking cessation date should be prepared, allowing arrangements for follow-up
It is important to see the patient the first day
or week of smoking cessation
Most relapse occurs within a few days of cessation
Provide behavioral support
Adjust the pharmacological treatment

Arrange
Arrange follow-up session within 7 days

For patients unwilling to quit
Clinicians should provide a brief intervention that is designed to promote the motivation to quit (the 5Rs)
Relevance
Risks
Rewards
Roadblocks
Repetition
Anderson J. Treating Tobacco Use and Dependence. An evidence-based clinical practice guideline. Chest 2002; 121:932-41 www.smokerclinic.com

Pharmacological therapy www.smokerclinic.com

Transdermal systems Acute systems www.smokerclinic.com Nicotine Replacement Therapy

NRT prescribing advice for 6 weeks
Indications
Reduction of withdrawal symptoms
Temporary abstinence
Reduced smoking to quit
NOT
Relapse prevention (yet?)
Long term maintenance
Side effects
Local (skin, mouth,nose)
GIT
Rarely AF, sleep disturbances
Contraindications
NONE
Cautions
Unstable CVS
Pregnancy / breastfeeding

Antidepressants
Bupropion SR: dopaminergic and noradrenergic profile
Mechanism of action for smoking cessation unknown
Possibly works via multiple mechanism
Efficacy comparable to NRT or even slightly superior
Nortriptylline
A tricyclic antidepressant with mostly noradrenergic properties
Effective but the limited number of trials and the side effects make it second-line intervention
Grade B Grade A Dose: 150mg/day (3-6 days) 150mg twice daily thereafter SOS : never >300mg/day 75mg/day www.smokerclinic.com

Bupropion prescribing
Indications
Reduced smoking to quit
NOT
Relapse prevention (yet?)
Long term maintenance
Side effects
Insomnia (40%)
Dry mouth (12%)
Hypertension
Urticaria
Seizure (1 in 1000)
Contraindications
Eating disorder
Seizure (FH)
Many drugs (steroids, theophyllines, antidepressants)
Pregnancy
Breast feeding

New Medications for Smoking Cessation
Nicotine Acetylcholine Receptors
n-ACh antagonists

Varenicline: A Highly Selective  4  2 Receptor Partial Agonist 1. Coe JW et al. Presented at the 11th Annual Meeting and 7th European Conference of the Society for Research on Nicotine and Tobacco. 2005. Prague, Czech Republic. 2. Picciotto MR et al. Nicotine Tob Res. 1999; Suppl 2:S121-S125. Binding of nicotine at the  4  2 nicotinic receptor in the VTA is believed to cause release of dopamine at the nAcc Champix is an  4  2 nicotinic receptor partial agonist, a compound with dual agonist and antagonist activities. This is believed to result in both a lesser amount of dopamine release from the VTA at the nAcc as well as the prevention of nicotine binding at the  4  2 receptors. Nicotine Chantix

Varenicline prescribing for 12 weeks
Indications
Relapse prevention in abstinent individuals
Side effects
GIT
Sleep disturbances
Abnormal dreams
Contraindications
Pregnancy
Cautions
Psychiatric
Renal impairment

Varenicline prescribing quit 500mcg 1 500mcg 2 3 days 4 days 1mg 2* reassess 11 weeks *reduce to 500 mcg 2 if side-effects but avoid abrupt withdrawal www.smokerclinic.com

4-Week Continuous Abstinence Response Weeks 9–12 1 30 0 10 20 40 50 60 VAR 1 mg bid (n=352) 44.0% BUP 150 mg bid (n=329) 30.0% Pbo (n=344) 17.7% OR VAR vs Pbo 3.85 P <0.0001 VAR vs BUP 1.89 P <0.0001 OR VAR vs Pbo 3.91 P <0.0001 VAR vs BUP 1.96 P <0.0001 VAR 1 mg bid (n=344) 44.4% BUP 150 mg bid (n=342) 29.5% Pbo (n=341) 17.7% 30 0 10 20 40 50 60 CA Response rate (%) Study 1 Study 2 VAR=varenicline, Pbo=placebo, BUP=bupropion; OR = Odds ratio. 1. Champix Summary of Product Characteristics. Pfizer Ltd, Sandwich, UK. 2006. Nausea was reported by 28.6% of patients treated with varenicline 1 mg bid. The discontinuation rate for this adverse event was 2.7%. Nausea was generally described as mild or moderate. CA Response rate (%)

New Treatments for Smoking Cessation
Cannabinoids Receptors Inhibitors (rimonaband ??)
Modifiers of nicotine metabolism (CYP2A6 inhibitors)
Nicotine Vaccines

Cannabinoid Receptor
Antagonists

Cannabinoid Receptors
The primary psychoactive constituent of marijuana, is related to the action on two cannabinoid receptors :
CB(1) and CB(2)
THE NECTAR OF DELIGHT www.smokerclinic.com

Weight and Smoking !! www.smokerclinic.com

Rimonabant is a CB 1 receptor antagonist
Blocks nicotine-induced reinforcement and self admin in animals (Cohen 2002)

Modifiers of
nicotine metabolism

Modifiers of nicotine metabolism
Inhibitors of CYP2A6
Nicotine Cotinine 3- hydroxycotinine CYP2A6 CYP2A6 www.smokerclinic.com

Cytochrome CYP2A6
CYP2A 6 Polymorfism (26 alleles)
Is Related with
Nicotine metabolism
Lower smoking initiation rate and lower smoking depedence
Lower smoking habit
Reduced risk for lung cancer

Other New Approaches for Smoking Cessation
Vaccination ????

Vaccines
Antibodies
bind to nicotine
Prevent nicotine
passing the
blood-brain barrier

Vaccines contd
TA-NIC, NicVax, Nicotine-Qbeta
Phase I and II complete, phase III expected 2008
Advantages: Not daily, few SEs, can be given alongside other medications?
But
Cost, variability, frequency dosing, slow onset, need high antibody titres, immune adaptation, ethical issues

Further Questions on New Treatments
More clinical trials and real phase studies to assess :
Effectiveness
Long term use
Relapse Prevention
Weight gain
Combined use

Sunrise in Nicotine Addiction Treatment www.smokerclinic.com

‘ True hope is like the crouched tiger, which will jump only when the moment for jumping has come. ’ Erich Fromm
For global tobacco control movement in every country of the world, the moment for jumping has come! www.smokerclinic.com

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Smoking Cessation

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