Transcript Nicotine dependence - University of Toronto

Nicotine 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)
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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
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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
VECTOR
HOST
AGENT
• Release of catecholamines increasing sympathetic
tone (GI motility, cardiac stimulation), argininevasopressin, 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
Peak nicotine concentrations are reached after
completion of cigarette smoking
Distribution
• 19 seconds to reach the brain
• Half-life: 2 hours
Metabolism and elimination
Liver and kidneys
Main metabolite: cotinine (70% - 80%)
CYP 2A6
plasma [nicotine] (ng/ml)
Pharmacokinetics of Nicotine
After Smoking
18
16
14
12
10
8
6
4
2
0
0
20
40
60
80
time (min.)
100
120
140
Neuropharmacology of Nicotine
Dependence
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nAChR’s
Dopaminergic system (reward)
Tolerance, physical dependence
MAO A and B
Smoking
initiation
Cigarette
Nicotine
Smoking
continuation
Smoking
discontinuation
Smoking
relapse
Active
nAChRs
Dopamine
release
Desensitized
nAChRs
Acute
tolerance
Inactive
nAChRs
Chronic
tolerance
Hyper excitable
nAChRs
Drive for the
next cigarette
Withdrawal
Increased no.
of AChRs
Reward
Pathological
learning
Perpetuation of
smoking
behaviour
Tobacco as a Drug of Abuse
DRUG
% ever used
% addiction
% risk
Tobacco
Alcohol
Illicit Drugs
Cannabis
Cocaine
Anxiolytics
Analgesics
Psychedelic
Heroin
75.6
91.5
51.0
46.3
16.2
12.7
9.7
10.6
1.5
24.1
14.1
7.5
4.2
2.7
1.2
0.7
0.5
0.4
31.9
15.4
14.7
9.1
16.7
9.2
7.5
4.9
23.1
Goodman and Gilman, 2001
Nicotine Withdrawal Syndrome
 Psychological
• Irritability
• Anxiety
• Aggressiveness
• Inability to
concentrate
• Depressed mood
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Physical
• Difficulty sleeping
• Increased appetite
• Headache
Drug (Nicotine) Dependence
DSM IV Criteria
1.
2.
3.
4.
Inability to stop using the drug
Preoccupation about drug use
Use despite harmful consequences
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
smoke you first cigarette
< 5 minutes
6 - 30 minutes
31- 60 minutes
After 60 minutes
3
2
1
0
2. Do you find it difficult to refrain from
smoking in places where is forbidden
e.g. in church, at the library, in cinema, etc.?
Yes
No
1
0
3. Which cigarette would you hate most to
give up?
The first one in
the morning
All others
1
0
4. How many cigarettes/day do you smoke?
10 or less
11-20
21-30
31 or more
0
1
2
3
5. Do you smoke more frequently during the
first hours after waking than during the
rest of the day?
Yes
No
1
0
6. Do you smoke if you are so ill that you
are in bed most of the day?
Yes
No
1
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
Bupropion
150mg twice/day 8-12 wks
Risk of seizures (>300mg)
Nortriptyline
Clonidine
Nicotine Blockade Therapy
Mecamylamine
Experimental approaches
GABA agonists (vigabatrin)
Factors Associated With
Low Quitting Success Rate
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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
plasma [nicotine] (ng/ml)
18
16
14
12
10
cigarette
gum
8
6
patch
4
2
0
0
100
200
300
time (min.)
400
500
600
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.