2. NICOTINE
• addictive drug
• causes mood-altering changes in the brain
• temporarily pleasing, making people want to use it
more and more
• When a person addicted to nicotine they have
unpleasant withdrawal symptoms, which temporarily
go away when they receive the nicotine
3. NICOTINE
• potent parasympathomimetic alkaloid found in the
nightshade family of plants (Solanaceae) and a stimulant
drug.
• nicotinic acetylcholine receptor agonist.
• It is made in the roots and accumulates in the leaves of
the plants. It constitutes approximately 0.6–3.0% of the
dry weight of tobacco and is present in the range of 2–
7 µg/kg of various edible plants.
• nicotine was widely used as an insecticide
4.
5. NICOTINE
• According to the American Heart Association,
nicotine addiction has historically been one of the
hardest addictions to break, while the
pharmacological and behavioral characteristics that
determine nicotine addiction are similar to those
determining addiction to heroin and cocaine.
10. E CIGARETTES
• benefits and health risk are uncertain.
• no evidence they are better than regulated medication for quitting
smoking
• safety risk is like that of smokeless tobacco
• US FDA approved products, such as nicotine inhalers, are
probably safer than e-cigarettes.
• While high voltage (5.0 V) e-cigarettes may generate formaldehyde
agents at a greater level than smoking when above a standard
setting.
• Nicotine is associated with cardiovascular disease,
potential birth defects, and poisoning.
15. . . . to relax; for the taste; to fill the time; something to
do with my hands
. . . . But, for the most part, people continue to smoke
because they find it too uncomfortable to quit’’
Philip Morris, 1984
Philip Morris. Internal presentation. 1984, 20th March; Kenny et al. Pharmacol Biochem Behav. 2001;70:
531-549.
16. The use of no
substance
Non-user
Trying a
substance a
few times
Experimental
use
• Once and
awhile
• Not regularly
done
• Not getting
drunk very
time
Occasional
use
•Routine
•Part of a design
ie every end of
the week,every
other weekend
•Doesn’t get
intoxicated
whenever
Regular
use
•Uses interferes
with functioning
•Loss of control
over amount
ones
uses/intends to
use
•Loss of control
of behaviour
ABUSE
•Routine
•Part of a style ie
every end
weekly
DEPENDANCY
S TA G E S O F S U B S TA N C E
D E P E N D A N C Y
17. Tobacco smoke
contains ~ 7000
compounds, most
of which are
highly toxic to the
human body
Tobacco is
extremely
addictive
20. Mechanism of Action of Nicotine in the Central
Nervous System
• The 42 nicotinic receptor in the VTA (Ventral Tegmental Area)
mediates the effects of nicotine in the central nervous system
• After nicotine binds to the 42 nicotinic receptor in the VTA, it
results in a release of dopamine in the nAcc, which is believed to
be linked to reward
nAcc= Nucleus Accumbens. Adapted from Picciotto et al. Nicotine Tob Res. 1999;1:S121-S125.
Nicotine -
Dopamine -
4 2
2
2
4
42
Nicotinic
receptor
nAcc
Ventral
tegmental area
(VTA)
NIC
23. T H E B R A I N H A S
N I C O T I N E R E C E P T O R S .
B U T U N L E S S Y O U
S M O K E , T H E S E A R E
“ A S L E E P ” .
Nicotine Receptor
24. W H E N Y O U S M O K E T H E
N I C O T I N E AT TA C H E S T O
T H E N I C O T I N E R E C E P T O R
Nicotine Receptor
Nicotine
25. T H I S R E S U L T S I N T H E R E L E A S E
O F D O P A M I N E W H I C H G I V E S A
G O O D F E E L I N G F O R A F E W
M I N U T E S
Nicotine Receptor
Nicotine
Dopamine
26. T H E M O R E O N E S M O K E S , T H E M O R E
N I C O T I N E R E C E P T O R S A R E
“ A W A K E N E D ” , M U L T I P L Y I N G T H E
G O O D F E E L I N G .
Nicotine Receptor
Nicotine Receptor Nicotine Receptor Nicotine Receptor
Nicotine
Nicotine
Nicotine
Nicotine
Dopamine
Dopamine
Dopamine
Dopamine
The number of
these receptors
increases after the
second dose of
nicotine
28. T H E “ L O W F E E L I N G ” C A N
S H I F T T O A N X I E T Y,
I R R I T A B I L I T Y, A N G E R ,
U N E A S I N E S S , H U N G E R …
Nicotine Receptor
Loss of
Dopamine
29. W H E N S E V E R A L R E C E P T O R S
F E E L L O S S O F D O P A M I N E , T H I S
R E S U L T S I N “ C R A V I N G ” F O R
N I C O T I N E .
Nicotine Receptor
Nicotine Receptor Nicotine Receptor Nicotine Receptor
Loss of
Dopamine
30. B Y S M O K I N G M O R E C I G A R E T T E S ,
M O R E D O P A M I N E I S R E L E A S E D
A N D T H E G O O D F E E L I N G I S
R E S T O R E D , B U T M O R E N I C O T I N E
R E C E P T O R S A R E N O W A C T I V A T E D .
Nicotine Receptor
Nicotine Receptor Nicotine Receptor Nicotine Receptor
Nicotine
Nicotine
Nicotine
Nicotine
Dopamine
Dopamine
Dopamine
Dopamine
Ksir C, Hakan R, Hall
DP, Kellar KJ (1985)
Exposure to nicotine
enhances the
behavioral stimulant
effect of nicotine and
increases binding of
[3H]acetylcholine to
nicotinic receptors.
Neuropharmacology
24:527–53
31. The Cycle of Nicotine Addiction
• Nicotine binding causes an increase in
release of dopamine
• Dopamine gives feelings of pleasure
and calm
• The dopamine decrease between
cigarettes leads to withdrawal
symptoms of irritability and stress
• The smoker craves nicotine to restore
pleasure and calmness
• Smokers generally titrate their smoking
to achieve maximal stimulation and
avoid symptoms of withdrawal and
craving
Jarvis. BMJ. 2004;328:277-279; Picciotto et al. Nicotine Tob Res. 1999;1:S121-S125.
Dopamine
Nicotine
32. • Developed tolerance and withdrawal
W I T H C H R O N I C U S E … .
DRUGS = REDUCE WITHDRAWAL
SYMPTOMS
DRUGS EUPHORIC EFFECT
33. M O D E L O F I M PA I R E D C O N T R O L
Addiction
Dopamine
Serotonin
Endorphins
GABA
Glutamate
Acetylcholine
34. Impulsivity
(automaticity)
Decision making
Neurobiological Basis for Relapse
Adinoff. Harv Rev Psychiatry. 2004;12:305-320.
Compulsive Drive
Circuits
Inhibitory Control
Deficits
Priming
Drug cues
Obsessive thoughts
(craving)
Stress
35. Nicotine Dependence: DSM-IV-TR Criteria
• 3 or more of the following symptoms within a 1-year time
span:
– Tolerance to nicotine with decreased effect and
increasing dose to obtain same effect
– Withdrawal symptoms with cessation
– Persistent desire to smoke despite efforts to decrease
intake
– Extensive time spent smoking or purchasing tobacco
– Postponing work, social, or recreational events in order
to smoke
– Continuing to smoke despite health hazards
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision. Washington, DC:
American Psychiatric Association; 2000; http://www.intox.org/databank/documents/supplem/supp/sup2.htm. Accessed October 19,
2007.
36. Role of Environmental Stimuli in Nicotine
Dependence
• Environmental/social stimuli associated with smoking play a
role in reinforcing nicotine dependence
• Non-nicotine stimuli are important in both motivating and
maintaining smoking behavior
• Role of environmental vs. pharmacologic stimuli in nicotine
dependence varies between men and women
Direct pharmacologic effects of nicotine are necessary but
not sufficient to explain tobacco dependence; these
effects must take into account the environmental/social
context in which the behavior occurs
Caggiula et al. Physiol Behav. 2002;77:683-687.
37. Nicotine Withdrawal
Restlessness
or impatience
Increased appetite
or weight gain
Withdrawal Syndrome
Anxiety
(may increase
or decrease
with quitting)
Dysphoric or
depressed mood
Irritability,
frustration,
or anger
Difficulty concentrating
Insomnia/sleep
disturbance
Nicotine withdrawal syndrome consists of both somatic and affective
symptomatology
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision. Washington, DC:
American Psychiatric Association; 2000.
38. 3.91
16.29
21.81
6.28 6.42
0
10
20
30
40
50
60
70
Severity of Withdrawal and Psychiatric
Disorders
aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.
Madden. Addiction. 1997;92(7): 889-902.
Smokers with a history of psychiatric disorders have a higher
likelihood of experiencing severe withdrawal
Alcohol
Dependence
Conduct
Disorder
Agoraphobia
Major
Depression
Social
Phobia
Odds
Ratio
(95%
CI)
a
42. K A E D A H R AWATA N
1.Nilai tahap kesediaan untuk berubah dan beri intervensi mengikut fasa
2.Strategi 5A atau 3A
3.Saringan Fagerstrom
4.Tetapkan Tarikh untuk berhenti
5.Persediaan mental, fizikal dan persekitaran
6.Petua 10 M
7.Langkah pencegahan relapse 5R
43.
44.
45. M U Z A K A R A H J A W A T A N K U A S A
F A T W A M A J L I S K E B A N G S A A N B A G I
H A L E H W A L U G A M A I S L A M
M A L AY S I A K A L I K E - 3 7 YA N G
B E R S I D A N G P A D A 2 3 M A C 1 9 9 5
T E L A H M E M B I N C A N G K A N H U K U M
M E R O K O K D A R I P A N D A N G A N
I S L A M . M U Z A K A R A H T E L A H
M E M U T U S K A N B A H A W A M E R O K O K
A D A L A H H A R A M D A R I P A N D A N G A N
I S L A M K E R A N A P A D A N YA
T E R D A P A T K E M U D H A R A T A N .
Editor's Notes
18
Schematic diagram of the human brain that highlights some of the main brain areas and neurotransmitter pathways implicated in reward processe.The ventral tegmental area, or VTA, is in the midbrain, situated adjacent to the substantia nigra. Although it contains several different types of neurons, it is primarily characterized by its dopaminergic neurons, which project from the VTA throughout the brain. The VTA is considered an integral part of a network of structures, together known as the reward system, that are involved in reinforcing behavior
The 42 nicotinic receptor in the VTA mediates the effects of nicotine in the central nervous system
After nicotine binds to the 42 nicotinic receptor in the VTA, it results in a release of dopamine in the nAcc, which is believed to be linked to reward
Nicotine causes an increase in the number of high affinity nicotinic cholinergic receptors in the brain structures associated with the reward pathway in both humans and rodents.30-33 The number of these receptors increases after the second dose of nicotine.31The increase parallels the development of tolerance, and receptor numbers decline after the drug is stopped coinciding with the withdrawal syndrome.30 33 That these high affinity receptors might play a role in dependence is also suggested by experiments with genetically altered mice.
Relapse occurs in response to stimulation by compulsive drive circuits and deficits in inhibitory restraint
Nicotine dependence is a well-defined addictive disorder
Nicotine’s effects on the 42 receptors in the Ventral Tegmental Area (VTA) results in
Acute dopamine release and short-term reward
Chronic receptor activation, desensitization, and up-regulation
The dopaminergically mediated physical and psychological rewards of smoking reinforce repeat behavior. Environmental/social stimuli associated with smoking play a role in reinforcing nicotine dependence
Nicotine withdrawal syndrome consists of both somatic and affective symptomatology
Smokers experiencing severe withdrawal have the most pronounced symptoms of depression
Smokers with a history of psychiatric disorders have a higher likelihood of experiencing severe withdrawal
