Post on 28-Dec-2015
Nicotine DependenceNicotine Dependence
Laurie Zawertailo, PhD
Adjunct Research Scientist
Clinical Neuroscience, CAMH
Objectives
1. To review the main physiological and pharmacological aspects of nicotine use, abuse, and dependence.
2. To discuss the different treatments available for nicotine dependence.
Cigarette Smoking (Statistics)
• 47% worldwide• 47% men• 12% women• 25% North America• 1/3 - 1/2 of adolescents daily smoking• 15% - 25% success rate to quit smoking
– Spontaneous quit rates in adults 6-7%
Costs of Tobacco Dependence• 30% (males) and 17% (females) of all cancer deaths
in Canada are due to smoking.• Over 25% of cancer burden in Canada is
attributable to lung cancer.• 80 - 90% of lung cancers are directly attributable to
smoking• Smoking is also directly linked to
– Diabetes– Heart disease– Stroke– Respiratory diseases– CV disease
Factors Associated With Smoking
• Biological hereditary, psychiatric, psychological
• Environmental parties, bars
• Social predisposition family, friends, cultural
• Easy access • Socially acceptable?• Peer pressure
Factors
ENVIRONMENT
HOST AGENT
VECTOR
• Release of catecholamines increasing sympathetic tone (GI motility, cardiac stimulation), arginine-vasopressin, beta endorphins, ACTH, cortisol, GH, PL, etc.
• Enhanced memory, task performance, concentration, attention, and anxiety reduction.
?
Clinical conditions associated with smoking:• Respiratory• Cardiovascular
Comorbidity:• Psychiatric disorders
Schizophrenia, depression, anxiety• Other drugs of abuse
Alcohol abuse/dependence
Nicotine
• Psychoactive drug contained in tobacco• Likely responsible for the addictive
properties of cigarettes• Self-administered by animals and humans• Reinforcing and rewarding• Following continuous administration the
reinforcing effects of nicotine become prominent and the control over its use is lost
Nicotine content in cigarettes:
6 – 11 mg (1-3 mg are absorbed)
Pack a day = 20 – 40mg
Smokers adjust their nicotine intake
High yield nicotine – less cigarettes
Low yield nicotine – more cigarettes
Pharmacology of Nicotine
Absorption • Buccal and nasal mucosa, skin, GI tract• Blood flow, membrane permeability, surface area, and pH
Other factors known to modify the rate of absorption:• Degree and depth of inhalation• Number, duration, and volume of puffs• Use of a filter• Number of cigarettes smoked• Time spent smoking each cigarette
Distribution • 19 seconds to reach the brain• Half-life: 2 hours
Metabolism and eliminationLiver and kidneysMain metabolite: cotinine (70% - 80%)CYP 2A6
Peak nicotine concentrations are reached after completion of cigarette smoking
Pharmacokinetics of Nicotine After Smoking
0
2
4
6
8
10
12
14
16
18
0 20 40 60 80 100 120 140
time (min.)
pla
sma
[nic
oti
ne]
(n
g/m
l)
Neuropharmacology of Nicotine Dependence
• nAChR’s
• Dopaminergic system (reward)
• Tolerance, physical dependence
• MAO A and B
Cigarette
Active nAChRs
Dopaminerelease
Smoking initiation
Desensitized nAChRs
Nicotine
Reward
Pathological learning
Inactive nAChRs
Acute tolerance
Smoking continuation
Hyper excitable nAChRs
Chronic toleranceSmoking
discontinuationWithdrawal
Drive for the next cigarette
Increased no. of AChRsSmoking
relapse
Perpetuation of smoking behaviour
Tobacco as a Drug of AbuseDRUG % ever used % addiction % risk
Tobacco 75.6 24.1 31.9
Alcohol 91.5 14.1 15.4
Illicit Drugs 51.0 7.5 14.7
Cannabis 46.3 4.2 9.1
Cocaine 16.2 2.7 16.7
Anxiolytics 12.7 1.2 9.2
Analgesics 9.7 0.7 7.5
Psychedelic 10.6 0.5 4.9
Heroin 1.5 0.4 23.1
Goodman and Gilman, 2001
Nicotine Withdrawal Syndrome
Psychological• Irritability• Anxiety• Aggressiveness• Inability to
concentrate• Depressed mood
Physical
• Difficulty sleeping• Increased appetite• Headache
Drug (Nicotine) Dependence DSM IV Criteria
1. Inability to stop using the drug
2. Preoccupation about drug use
3. Use despite harmful consequences
4. Presence of symptoms accounting for brain adaptation resulting in persistence use of the drug
5. Use despite significant drug-related problems
Fagerström Test for Nicotine Dependence
Questions Answers Points 1. How soon after you wake up do you < 5 minutes 3 smoke you first cigarette 6 - 30 minutes 2 31- 60 minutes 1 After 60 minutes 0 2. Do you find it difficult to refrain from Yes 1 smoking in places where is forbidden No 0 e.g. in church, at the library, in cinema, etc.? 3. Which cigarette would you hate most to The first one in 1 give up? the morning All others 0
4. How many cigarettes/day do you smoke? 10 or less 0 11-20 1 21-30 2 31 or more 3 5. Do you smoke more frequently during the Yes 1 first hours after waking than during the No 0 rest of the day? 6. Do you smoke if you are so ill that you Yes 1 are in bed most of the day? No 0
Treatments for Nicotine Dependence
Behavioural Intervention Therapies
Individual behavioural counseling
Nicotine fading
Aversion treatments
Acupuncture
Hypnosis
Nicotine Replacement Therapies
Patch (7, 14, 21, 22mg) 6-12 wks
Gum (2 and 4mg) 8-12 wks
Inhaler (4mg/cartridge) 6 – 16/day 3-6 mo
Nasal spray (1-2/hr; 0.5mg each; max 40mg/day) 3-6mo
Low yield cigarettes
Bupropion150mg twice/day 8-12 wksRisk of seizures (>300mg)
Nortriptyline
Clonidine
Nicotine Blockade TherapyMecamylamine
Experimental approachesGABA agonists (vigabatrin)
Factors Associated With Low Quitting Success Rate
• Comorbid psychiatric conditions
• Alcohol or substance abuse
• High nicotine dependence
• Lack of social support for quitting
• Low self-confidence in ability to quit
Pharmacokinetics of NRT
0
2
4
6
8
10
12
14
16
18
0 100 200 300 400 500 600
time (min.)
pla
sma
[nic
oti
ne]
(n
g/m
l)
cigarette
gum
patch
Treating Tobacco Dependence
• Smoking is a complex human behaviour
• Often takes several quit attempts before one is successful
• NRT is most successful when combined with supportive care.
• Lapse and relapse is very common.