Smoking Cessation

Smoking Cessation !! How to become a real option ????

Dr. Assem Fouad El EsssawyLecturer 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:S144www.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 42 nicotinic receptor in the Ventral Tegmental Area (VTA)

• After nicotine binds to the 42 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 2224

42Nicotinic 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.


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


Practical steps


“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


CO measure is useful for reinforcing patient’s motivation to quit

Modified Fagerstrom1991


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 cessationProvide 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


Pharmacological therapy


Transdermal systems Acute systems


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/daywww.smokerclinic.com

Bupropion prescribing

Indications – Reduction of withdrawal

symptoms– 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 Receptorsn-ACh antagonists


Varenicline: A Highly Selective 42 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 42 nicotinic receptor in the VTA is believed to cause release of dopamine at the nAcc

Champix is an 42 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 42 receptors.

Nicotine Chantix

Varenicline prescribing for 12 weeksIndications – Reduction of withdrawal

symptoms

– Relapse prevention in abstinent individuals

Side effects– GIT– Sleep disturbances– Abnormal dreams

Contraindications•Pregnancy

Cautions•Psychiatric•Renal impairment


Varenicline prescribing

quit

500mcg1500mcg2

3 days 4 days

1mg2*

reassess

11 weeks

*reduce to 500 mcg2 if side-effects but avoid abrupt withdrawal


4-Week Continuous Abstinence Response Weeks 9–121

30

0

10

20

40

50

60

VAR1 mg bid(n=352)

44.0%

BUP150 mg bid

(n=329)

30.0%

Pbo(n=344)

17.7%

ORVAR vs Pbo 3.85 P<0.0001VAR vs BUP 1.89 P<0.0001

OR VAR vs Pbo 3.91 P<0.0001VAR vs BUP 1.96 P<0.0001

VAR1 mg bid(n=344)

44.4%

BUP150 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 DELIGHTTHE NECTAR OF DELIGHT


Weight and Smoking !!


• Rimonabant is a CB1 receptor antagonist

• Blocks nicotine-induced reinforcement and self admin in animals (Cohen 2002)



Modifiers ofnicotine metabolism


Modifiers of nicotine metabolism

• Inhibitors of CYP2A6

Nicotine Cotinine

3-hydroxycotinine

CYP2A6

CYP2A6


Cytochrome CYP2A6

• CYP2A6 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



• ‘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!



Health & Medicine

Smoking Cessation