4. DEPENDENCE
• Strong desire to take the drug
• Difficulties in controlling its use
• Persistent use despite harm
• Higher priority to drug rather than other activities
• Increased tolerance
• Withdrawal symptom after stoppage
(International Classification of Disease - 10)
• Recent concept : Drugs addiction is a chronic
disease of brain
5. Addiction
"a chronic relapsing disease characterized by compulsive
drug-seeking and abuse and by long-lasting chemical
changes in the brain" (NIDA-2002)
Being abnormally tolerant & dependent on
something that is psychologically or physically
habit forming.
(WHO-2oo8)
(it is scientifically used for other than the Substances e .g:
TV, Money & Power, Cyber etc)
(WHO-1964)
6. Substance Abuse & Intoxication
Abuse: Recurrent use of Substances
despite of physiological hazards with social,
interpersonal and legal problems.
Intoxication: Clinically Significant
maladaptive behavioral or psychological
changes that are due to the effect of the
substance on the CNS and develop during
or transiently after use of the Substance.
7. Definition of Tolerance
Need for markedly increased amounts of the
substance to achieve desired effect.
Or reversely we can consider it –
Markedly diminished effect with continued use
of the same amount of
Substance.
Cross Tolerance:
Development of tolerance of
to one substance as the result
of using another one.
(i. e: Max pt. of our M/W)
8. Withdrawal
• Adaptive changes become fully apparent/focused
once drug exposure is terminated.
This state is called withdrawal and is observed to
varying degrees after chronic exposure to most
drugs of abuse or dependence.
(Globally w . syndrome has different panicky
Synonyms among the Abusers, i.e- Bera, Raadha)
9.
10. Genetic component of
common traits
Trait Heritability
Type II (adult-onset) diabetes 0.31
Type I (insulin-dependent) diabetes 0.72
Hypertension 0.3 - 0.53
Peanut allergy 0.84
Cataract (age-related) 0.55
Alcoholism 0.66
Nicotine 0.5 – 0.67
Cocaine and stimulants( e. g.: Amphetamine) 0.4 – 0.88
Heroin and opiates 0.59
Marijuana 0.3 – 0.810
11.
12. The “Gateway” or Stage
Theory
Related
With This theory comes from
Genetic epidemiological research.
Loading Adolescents engage in use of either
or alcohol or cigarettes (as legal and
Predisposition culturally accepted drugs) then
progress to marijuana, amphetamine
and then on to other illicit drugs, such
as heroin and cocaine. (Kandel, 1975
).
13. Problem Behavior Theory
• The theory proposes that there exists a
syndrome of adolescent problem
behaviours that may co-occur within
the same individual (Jessor, 1991).
Usually 3 types of problem
behaviours:-
14. Truancy
Petty theft Delinquent • Risky and
precocious
Vandalism Behaviour sexual activity
Lying
Running
away
Other
High Risk
Behaviour
Driving drunk , Drag racing
15. Patterson's Developmental Theory
• Patterson's theory was originally
proposed to explain the
development of “juvenile
delinquency”, and however
consistent with the observation.
16. Other Etiology
Psychodynamic Factors: Substance abuse is a
defense against anxious impulses (Freudian Defense Mechanism)
Personality Traits and disorders: Many traits are predisposed
with taking substances. Among the Personality disorders, Cluster –B
has profound relation specially Anti-social Personality is moved to the
highest position (Co-morbidity up to 60%)
Borderline P.D., Narcissistic
& also Anxious avoident personality,
17. According The
to the types Mechanistic
of Action Classification
upon CNS of Substance
According
to the
Mode of
Dependency.
18. According to the types of Action upon CNS
Nervous System Nervous System
Depressants Stimulants
Alcohol Amphetamines
(In BD- Yaba,Ind-Champa
Arab- Kreptagone,usa-Spd
Cannabis (Gaja) Cocaine, Anabolic Steroid
Opioids (phensidyl, heroin, Tobacco
pethedrine)
Benzodiazepines (Valium)
Barbiturates
19. TYPES
Drugs with physical & Drugs with psychological
psychological dependence dependence
Alcohol Cannabis (Hasis,Gaja)
Opioids (Phensidyl, Heroin) Amphetamines(YABA)
Barbiturates Cocaine
Benzodiazepines (Valium)
Tobacco
(Gelder et al, 2000)
20. The Mechanistic Classification of
Substance
Drugs activating G-Protein coupled receptors
Name Mode of Action Effect on
Dopamine (DA)
(Pharmacology) Neurons
Opioid & Agonist Disinhibition
Canabinoids
LSD, GHB Partial Agonist Disinhibition
21. Drugs That Bind to Ionotropic (Gaba.R, Ach.R,
NMDA.R) Receptors and Ion Channels
Name Mode of Action Effect on
Dopamine (DA)
(Pharmacology) Neurons
Nicotin Agonist Excitation
Alcohol Excit. &
Disinhibition
Benzodiazepine Partial Agonist Disinhibition
Ketamine
22. Drugs That Bind to Transporters of
Biogenic Amines
Name Mode of Action Effect on
Dopamine (DA)
(Pharmacology) Neurons
Amphetamine Reverses Blocks DA
Ecstasy transport uptake, synaptic
depletion
Inhibitor Blocks DA
Cocaine uptake
23. Volatile / Inhalant substances
Volatile / Mode of action Effect on NMDA receptors
Inhalant
substances
Spray Exhibits a variety of NMDA receptors antagonist,
paint,Cleaning Mechanism ,still not bind inside the ca-channels and
agent even well elucidated. outer surface of neuron.
Room
odorizers,Glue,
SISA
29. Circuits Involved In
Drug Abuse and Addiction
CONTROL PFC
INHIBITORY
CONTROL ACG
OFC Hipp
SCC REWARD
NAc
MOTIVATION/
c VP
DRIVE
Amy
g
MEMORY/
LEARNING
34. d
p pe
tra
,en .
l s th ts.
gir wi alen
Eli t e / inh
i le
la t
Vo
35. REASONS
i. Availability of drugs
ii. Curiosity (From family & surroundings,just for thrill)
iii. Friends taking drugs (Peer pressure)
(Delinquent peer group highly influential on SA development)
iv. Pleasure Seeking (Lack of other recreation or amusements)
v. Frustration (From Unemployment /Distorted F.Sturcture)
vi. Disregard for values (Especially in Western culture)
vii. Some may think that they might be immune and the effects of
drugs won’t affect them.
viii. When some people are stressed and need something to get them
past their problems they may take drugs.
36. CYCLES OF ADDICTION
Drug intake Feels well (primary reward)
Conditioning Distress if not taken
(e.g. sour &
salivation)
Takes again to avoid distress
(2ndary reward)
Friends encouraging
drug taking
(social reward)
37. Diagnosis
• Evaluate medical condition including
complications (LFT, STDs)
• Generate differential diagnosis for
psychiatric/medical symptoms
• Utilize urine ,Blood and hair /nail (Prolong user)
for toxicology screening.( In our set up only
Urine, even all reagent not available,
i.e: Alcohol, Inhalants(SISA) etc)
38. CONSEQUENCES
Physical
• Hepatitis (HbsAg), AIDS-IDUs, cirhosis of liver-
Alcoholics,STDs,memory impairment-
Amp.,Hero,Cocaine,Volatiles…
Psychological
• Madness(Psychosis), depression, suicide, sexual
dysfunction-preferably E.D & Orgasmic Failure.
Social
o Academic failure, unemployment, job loss, prestige loss,
divorce, separation, In chaste
o Criminal involvement- snatching, hijacking, arms, illegal
sex.
40. MANAGEMENT PLAN
• Early detection & motivation
• Hospitalization & detoxification
• Treatment of mental disorders
• Life style changes
• Counseling
• Follow up & rehabilitation
41. Management
• Prevention and Early Intervention
-- Aggressive psycho-education to parents and child
regarding SA (start <21yrs.)
-- Discussion of known risk factors (i.e. conduct
disorder)
-- Aggressive Tx of psychopathology
-- Close monitoring in high risk cases (tobacco use,
questionnaires, urine toxicology)
42. Management-Cont.
• Parent Works are the followings-
-- Need for involvement
-- Need for increased supervision
-- Behavioral management techniques
-- Need to monitor SA & Psych Treatment.
-- Establish additional supports
* AA/NA/AI-Anon (Self help group)
(In BD-Not exactly in the similar form but modified
S.H.G available in society.)
43. PREVENTION
1. Supply Reduction
- Control of air port, sea port, land port &
internal trafficking
- Control of illicit production
- Crush programme
2. Demand Reduction
- Drugs are available but people will not take
- Intervention with individual demand
3. Harm Reduction
- Early detection & treatment
46. Captagon (Amphetamine)
History of Amphetamine
Epidemiology & Routes
Quantity & Quality,Derivatives
Mechanism of Action of Amphetamine
Sign & Symptoms of Amphetamine
Misdiagnosis in our (Al-Jouf) OPD
Management (Treatment)
47. History
• Amphetamine-first synthesized in1887 by Romanian
chemist Lazăr Edeleanu.
• OTC use of amphetamines were for- colds,
nasal congestion & as bronchodilator .
• The reinforcing effects of amphetamines were quickly
discovered, and the misuse of amphetamines started--
• During World War II, amphetamines were used by the
military to keep soldiers awake.
• The widespread misuse of amphetamines began in the post
war Japan and quickly spread to other countries.
48. Epidemiologic differences
of Amphetamine related Psychiatric Disorders
Race
Amphetamine-related psychiatric disorders (ARPD)
most commonly occur in white individuals .
Sex
With IV use, Psychiatric disorders commonly occur
in men, with a male-to-female ratio of 3-4:1.With
non-IV use -1:1.
Age: Most frequently found around 20-
39 yrs at rave parties and dance clubs.
Also >40 to onwards available.
49. Routes of administration
Intravenous injection: is the fastest
mechanism, known as “Slamming”
methamphetamine salt 100mg -1gm
By
using a hypodermic needle.
o Smoking: By vaporizing it to inhale
the resulting fumes, not burning it to
inhale the resulting smoke
"chasing the white dragon"
Insufflations (snorting): where a user crushes
the methamphetamine into a fine powder and
then sharply inhales it.
50. Quantity, Quality & Manufacture
Purity: Overall range in purity for amphetamine is
up to 66%, and for methamphetamine up to 80%.
Adulteration:--
Caffeine : Amphetamine covered by caffeine.
Fenethylline : Covered by fenethylline.
Available in Al-Jouf, UNODC reports that GULF regions
Captagone pills mix with the Caffeine, Fenethylline & others.
Pseudo-ephedrine
Commonly marketed in
Hypo-phosphorous Uk, Australia & USA
51. Common Derivatives of Amphetamine
• Amphetamine (α-methylphenylethylamine)
• Methamphetamine (N-methylamphetamine)
• Ephedrine pseudoephedrine
• Cathinone-β-Ketoamphetamine (Khat)
All above four are available in Al-Jouf .
• Methcathinone (ephedrone)
• MDA (3,4-methylenedioxyamphetamine)
• MDMA (3,4-methylenedioxymethamphetamine)
• MDEA (3,4-methylenedioxy-N-ethylamphetamine)
52. Various Types of Amphetamine Derivatives
with different colours & impressions with in it,
The Blueish and greenish ones are available in BD.
56. Normal Mechanisms
• In the normal operation, synaptic release of
catecholamines is carried out by exocytosis
of a vesicle which contain a
neurotransmitter. Then, the neurotransmitter
is reabsorbed from the synaptic cleft into
the cytoplasm of the neuron. From the
cytoplasm, the neurotransmitter penetrates
back into the vesicles via the action of the
vesicular monoamine transporter (VMAT).
57.
58. Mechanism of amphetamine action. Left: Normal operation
of dopaminergic terminal. Right: Dopaminergic terminal in presence of
amphetamines showing the reversal of action of the dopamine transporter
(DAT) and the vesicular monoamine transporter (VMAT) and the decrease of
the standard vesicular neurotransmitter efflux.
59. Mechanism after taking
Amphetamine
• The stimulating effect of amphetamines is mainly
associated with an increased emissions ---of C
atecholamines Norepinephrine and Dopamine.
• Presence of amphetamine and its derivative inverts
the direction of the transport: neurotransmitter
moves from vesicles to the cytoplasm and then to
the synaptic cleft. As a result, vesicles are
emptied, vesicular release of neurotransmitter is
reduced, and the concentration of neurotransmitter
in the synaptic cleft increases.
60. Sign & Symptoms
• autonomic nervous system is mainly due to
emissions of norepinephrine. This enhances
stimulation of α-and β-adrenoreceptors that
can lead to tachycardia (increased heart
rate), elevated blood pressure, mydriasis
(dilated pupils), sweating and hyperthermia
(elevated body temperature)
61. The list of signs and symptoms mentioned in various sources for
Amphetamine abuse includes >70 symptoms with >5 phases --------
Stimulation
phase
Reaction
Addiction phase
Phase Withdrawal
(coming
Phase down)
Toxic Severe
Phase Phase
62. Stimulation phase symptoms may include
(symptoms vary greatly between people)
Raised blood
Important Symptoms
From ANS
– Alertness (Sleepless) pressure
– Energetic Dry mouth
– Exhilaration Pupil dilation
– Excitement Headaches
– General feeling of wellness Sweating
– Increased confidence Talkative
– Feeling of superiority Restlessness
– Reduced appetite Difficulty sleeping
– Raised pulse Anxiety
– Rapid breathing Irritability
Aggression
69. Mental status of a patient with amphetamine intoxication is as follows:
– Appearance and behavior: Unusually friendly,
scattered eye contact, buccal oral gyrations,
excoriations on extremities and face from picking at
skin, overly talkative and verbally intrusive
– Speech: Increased rate( in AIPD)
– Thought process: Tangential, circumstantial over
inclusive and disinhibited (Guarded in AIPD)
– Thought content: Occasional Paranoid; no suicidal
or homicidal thoughts usually
– Mood: Anxious, hypo manic
– Affect: Anxious and tense (Paranoid in AIPD)
– Insight and judgment: Poor
– Orientation: Alert to person, place, and purpose;
perspective of time is disorganized
71. Investigations
Laboratory Studies-
– CBC, RBS, LFT, RFT, Total protein, uric acid, Bilirubin
– Urinalysis Single Panel
Meth/Amphetamine
Drug Test tool
Stat urine or serum toxicology screening
HIV and Rapid Plasma Reagin (RPR) tests
Psychometric-BPRS, B.Dep.Scale, Viol & Sui.Assessm Scale,AIMS-for
AWS, MMSE-for cog imp in AIS, even TAT also for P. imp.
Imaging Studies (Histological change)
• Neurologic impairments-By CT or MRI (Suba & ICH)
72. Vicious
Cycle of
Amphetamine length of
Dependence dendrites
From histological findings
Repeated
exposure
Psychosis to
amphetamines
tex al
Nu umb
acc
t
fron
cle ens
us
Pre
cor
Behavioural
.
cravings
73.
74. Rx of
Amp Ind. Disorders
Intoxication With Anxiety
(neurotic)
With Psychotic
Symptoms
Syndrome Symptoms
Induced emesis by Ammonium Better to treat by
If few, we may wait
lavage,or charcoal, Chloride(Quelidrine) non-diazepines Anx
for Self limitation
Open i/v channel To Acidify urine Propanolol(<120-200)
500 mg every 2-3 hours.
(N.A in ouPharmacy,Expectorant)
Lorazepam, Cholordiazepoxide Anti-Depressants Anti-psychotic , Anti-manic
propanolol and also Naltrexone If need Benzodiazepines Even Naltrexone
75. Consultation
• Neurologist
• Internal medicine specialist
• Hepatologist
• Psychiatrist: Consult for inpatient substance abuse
treatment or further psychiatric stabilization.
• Social services: Social services coordinate
outpatient services, such as Narcotics Anonymous
meetings and sober houses.
76. Complications of Amp.
Ind. Disorders
– Psychosis
– Depression
– Anxiety disorder
– Sleep disturbance
– Memory impairment
– Medical complications
– Neurologic complications (i.e-Ayed Bashir)
– Abuse of another or several substances-Most
common in our Ward
– Psychosocial & pers. impairment ( also common-AA.K)
77. Prognosis
o The patient's prognosis depends on the severity of
psychiatric impairment and on the medical
complications.
o Overall, the prognosis is good if the patient abstains
from drug use after the initial psychiatric impairment
occurs.
o The prognosis worsens if personality disorders are
present.
78.
79. Ghat / Khat
One of the popular Derivatives of
Amphetmine (Kreptagone) which is
basically Cathinone
• Natives of Yemen and Ethiopia have a long
tradition of chewing Ghat leaves to achieve
a stimulating effect. The active substances
of khat are cathinone and to a lesser extent
cathine
Notes de l'éditeur
From Jonathan Pollock’s Genetics & Addiction pres sent 5/13/02 References: 1 Poulsen et al., Diabetologia 1999; 42:139-45 2 Kyvik et al., BMJ 1995; 311:913-7, 3 Cited in: Corvol & Jeunemaitre, Endocrine Reviews, 1997, p. 662-677 4 Sicherer et al., J Allergy Clin Immunol 2000; 106:53-6 5 Hammond et al., N Engl J Med 2000; 342:1786-90 6 Cited in: Goate & Edenberg, Curr Opin Genet Dev.1998; 8:282-6. 7 Cited in: Sabol et al., Health Psych. 1999; 18:7-13. 8 Tsuang et al. 1996; Am J Med Genet. 1996; 67:473-7; Kendler & Prescott, Br J Psychiatry 1998; 173:345-50. 9 Tsuang et al. 1996; Am J Med Genet. 1996; 67:473-7 10 Tsuang et al. 1996; Am J Med Genet. 1996; 67:473-7; Kendler & Prescott 1998; Am J. Psychiatry 155:1016-22
Slide 27: Dopamine binding to receptors and uptake pumps in the nucleus accumbens; the action of cocaine Explain that cocaine binds to sites in areas of the brain that are rich in dopamine synapses such as the VTA and the nucleus accumbens. Review dopamine transmission in the close-up of a synapse in the nucleus accumbens. Point to dopamine (inside the terminal) that is released into the synaptic space. The dopamine binds to dopamine receptors and then is taken up by uptake pumps back into the terminal. Now show what happens when cocaine is present (yellow). Cocaine binds to the uptake pumps and prevents them from transporting dopamine back into the neuron terminal. So more dopamine builds up in the synaptic space and it is free to activate more dopamine receptors. This is the same effect that you showed in an earlier slide with morphine, where morphine increased dopamine release from the terminal to produce more dopamine in the synaptic space.
Slide 7: The synapse and synaptic neurotransmission Describe the synapse and the process of chemical neurotransmission. As an electrical impulse arrives at the terminal, it triggers vesicles containing a neurotransmitter, such as dopamine (in blue), to move toward the terminal membrane . The vesicles fuse with the terminal membrane to release their contents (in this case, dopamine). Once inside the synaptic cleft (the space between the 2 neurons) the dopamine can bind to specific proteins called dopamine receptors (in pink) on the membrane of a neighboring neuron. This is illustrated in more detail on the next slide.