Dr. M. S. KABIR JEWEL

PSYCHIATRIST

OUTLINE

Definitions

Causes

Types of Substance

Mechanism of Action

Magnitude in Dhaka,Bangladesh

Consequences

Management

Substance :(means psychoactive substance): That can cause addiction, a marked change in mental status, or psychological / physical dependency.

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

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)

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.

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.

Definition of Tolerance

Cross Tolerance: Development of tolerance of to one substance as the result of using another one.(i. e: Max pt. of our M/W)

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)

Genetic component of common traits

Trait HeritabilityType 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

The “Gateway” or Stage Theory

This theory comes from epidemiological research.

Adolescents engage in use of either alcohol or cigarettes (as legal and

culturally accepted drugs) then progress to marijuana, amphetamine

and then on to other illicit drugs, such as heroin and cocaine. (Kandel, 1975

).

Related With

GeneticLoading

orPredisposition

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:-

•  Risky and precocious

sexual activity

Other High RiskBehaviour

Delinquent Behaviour

Truancy Petty theftVandalismLying Running away

Driving drunk , Drag racing

Patterson's Developmental Theory

• Patterson's theory was originally proposed to explain the development

of “juvenile delinquency”, and however consistent with the

observation.

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,

According to the types of Action upon CNS

The Mechanistic

Classification of Substance

According to theMode of Dependency.

According to the types of Action upon CNSAccording 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 (Joyce et al, 1997)

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)

The Mechanistic Classification of Substance

Drugs activating G-Protein coupled receptors

Name Mode of Action

(Pharmacology)

Effect on Dopamine (DA) Neurons 

Opioid & Canabinoids

Agonist Disinhibition

LSD, GHB Partial Agonist Disinhibition

Drugs That Bind to Ionotropic (Gaba.R, Ach.R, NMDA.R) Receptors and Ion Channels

Name Mode of Action

(Pharmacology)

Effect on Dopamine (DA) Neurons 

NicotinAlcohol

Agonist Excitation Excit. & Disinhibition

Benzodiazepine

Ketamine

Partial Agonist Disinhibition

Drugs That Bind to Transporters of Biogenic Amines 

Name Mode of Action

(Pharmacology)

Effect on Dopamine (DA)

Neurons 

Amphetamine Ecstasy

Reverses transport

Blocks DA uptake, synaptic

depletion

Cocaine

Inhibitor Blocks DA uptake

Volatile / Inhalant substances

Volatile / Inhalant substances

Mode of action Effect on NMDA receptors

Spray paint,Cleaning agent even Room odorizers,Glue,

SISA

Exhibits a variety of Mechanism ,still not well elucidated.

NMDA receptors antagonist, bind inside the ca-channels and outer surface of neuron.

Normal Physiology

Substance (Amphetamine etc), which areas are involved in Brain?

Molecular action of “Amphetamine”(Gross view)

PFCPFC

ACGACG

OFCOFCSCCSCC

HippHipp

NAccNAccVPVP

Amyg

Amyg

REWARDREWARD

CONTROL INHIBITORY

CONTROL

CONTROL INHIBITORY

CONTROL

MOTIVATION/DRIVE

MOTIVATION/DRIVE

MEMORY/LEARNING MEMORY/

LEARNING

Circuits Involved In Circuits Involved In Drug Abuse and AddictionDrug Abuse and Addiction

Circuits Involved In Circuits Involved In Drug Abuse and AddictionDrug Abuse and Addiction

Magnitude

0%

10%

20%

30%

40%

50%

60%

1stQtr

3rdQtr

AmphetamineCanabinoidInhalent(Betix)Alcohol

BenzodiazepineMixedAbuser

% Of Different Substances among Admitted patients in our De-addiction Hospital/Clinics , Dhaka BD.

ROUTES

• Oral - amphetamine (Yaba),

(Street Name- Champa,R etc)

Benzodiazepine(Ativan,Valim,Xanax)

Phensidyl(Codine phosphate).

Snifffing – Heroine (Chasing the dragon)

• Smoking - Cannabis (Hasish), Heroin .

• Inhalation/Volatile – Glue/SISA-spreading now fastly.

• Intravenous (IDU)- Pathedrine ,Morphine(e.g:TDJesic) benzodiazepine

Street

boys,

preparing

heroine….

Elite girls ,

entrapped

with

Volatile/in

halents..

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.

REASONS

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)

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)

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.

Socialo Academic failure, unemployment, job loss, prestige loss,

divorce, separation, In chaste o Criminal involvement- snatching, hijacking, arms, illegal

sex.

Psychiatric Disorders due to Substance Abuse

Substance induced psychotic disorder.Substance induced mood disorderSubstance induced anxiety disorder Substance induced sleep disorder Substance induced sexual disorder/ perverted too.

Substance induced dementia/delirium Substance induced other organic B.syndrome

MANAGEMENT PLAN

• Early detection & motivation

• Hospitalization & detoxification

• Treatment of mental disorders

• Life style changes

• Counseling

• Follow up & rehabilitation

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)

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.)

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

Thanks a lot for attending me

History of Amphetamine

Epidemiology & Routes

Quantity & Quality,Derivatives

Mechanism of Action of AmphetamineMechanism of Action of Amphetamine

Sign & Symptoms of AmphetamineSign & Symptoms of Amphetamine

Misdiagnosis in our (Al-Jouf) OPDMisdiagnosis in our (Al-Jouf) OPD

Management (Treatment)

CaptagonCaptagon (Amphetamine)(Amphetamine)

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.

Epidemiologic differencesof Amphetamine related Psychiatric Disorders

RaceAmphetamine-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.

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""chasing the white dragon"

Insufflations (snorting): where a user crushes the methamphetamine into a fine powder and then sharply inhales it.

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 Hypo-phosphorous

Commonly marketed in Uk, Australia & USA

Common Derivatives of AmphetamineCommon 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)

Various Types of Amphetamine Derivatives with different colours & impressions with in it,The Blueish and greenish ones are available in BD.

Major areas of brain usually Affected by Amphetamine

Normal Brain molecular pathwayNormal Brain molecular pathway

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).

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.

Mechanism after taking Amphetamine

• The stimulating effect of amphetamines is mainly associated with an increased emissions ---of Catecholamines 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.

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)

The list of signs and symptoms mentioned in various sources for Amphetamine abuse includes >70 symptoms with >5 phases --------

AddictionPhase

Toxic Phase

SeverePhase

Reaction phase

(coming down)

Stimulation phase

WithdrawalPhase

Stimulation phaseStimulation phase symptoms may include (symptoms vary greatly between people)

Important Symptoms– Alertness (Sleepless)– Energetic– Exhilaration– Excitement– General feeling of wellness– Increased confidence– Feeling of superiority– Reduced appetite– Raised pulse– Rapid breathing

Raised blood pressure

Dry mouthPupil dilationHeadachesSweatingTalkativeRestlessnessDifficulty sleepingAnxietyIrritability

Aggression

From

AN

S

Reaction phase (coming down)

– Depressed mood– Tiredness– Violent behavior– Moodiness– Mood swings– Physical exhaustion– Tension

Mimics With Canabinoids

&MDDIe:A.R.M,H.Ayed

Symptoms of amphetamine addiction

– Paranoia

– Delusions

– Hallucinations

– Severe anxiety

– Poor judgement

– Depression

– Suicidal thoughts

– Suicide

– Exhaustion

– Weight loss

• Malnutrition

S/S in a nutshell

Symptoms of amphetamine withdrawal

– Irritability

– Hunger

– Fatigue

– Anxiety

– Depressive symptoms

– Over-sleeping

– Restless sleep

– Nightmares

– Panic

DSM-IV-TR describes the following 10 amphetamine-related psychiatric disorders 

• Amphetamine-induced anxiety disorder• Amphetamine-induced mood disorder----------• Amphetamine-induced psychotic disorder with delusions----------------------------------• Amphetamine-induced psychotic disorder with hallucinations----------------------------• Amphetamine-induced sexual dysfunction• Amphetamine-induced sleep disorder-----------• Amphetamine intoxication-------------------------• Amphetamine intoxication delirium• Amphetamine withdrawal –Few, due to lack of purity (up-to 35% mixed

with Caffeine-ie: Abu –Reeha, Lemis)

• Amphetamine-related disorder not otherwise specified

Common in our Al-Jouf OPD from Lexis &Abu Hafera

On MSE specially in Appearance & Behaviors ?

For a Amp. Dependent

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

Differential DiagnosesDifferential Diagnoses

• Cannabis Compound Abuse• Cocaine-Related Psy.

Disorders• Delirium• Depression• Hallucinogens• Hyperthyroidism• Hypothyroidism• Inhalant-Related Psy.

Disorders• Insomnia

Opioid Abuse Phencyclidine (PCP)Related

Psychiatric Disorders Schizophrenia Adj.Disorder with cond prob

(common in our OPD ie K.md) Toxicity, Heroin Toxicity, Mushroom WernickeKorsakoff SyndromeOther problems-- AIDS-related complex Thyrotoxicosis Syphilis

Investigations

Laboratory Studies-– CBC, RBS, LFT, RFT, Total protein, uric acid, Bilirubin– Urinalysis

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)

Single Panel Meth/Amphetamine Drug Test tool

Repeated exposure

to

amphetamines

Behavioural cravings

Psychosis

Pre

fron

tal

cor

tex

Nucleus

accumbens.

length of dendrites

Vicious Cycle of

AmphetamineDependence

Fro

m h

isto

logi

cal f

ind

ings

Rx of Amp Ind. Disorders

IntoxicationSyndrome

With Anxiety(neurotic) Symptoms

With Psychotic Symptoms

If few, we may wait for Self limitation

Induced emesis by lavage,or charcoal,

Open i/v channel

Better to treat by non-diazepines Anx

Propanolol(<120-200)

Lorazepam, Cholordiazepoxidepropanolol and also Naltrexone

Anti-psychotic , Anti-manicEven Naltrexone

Anti-DepressantsIf need Benzodiazepines

Ammonium Chloride(Quelidrine)

To Acidify urine500 mg every 2-3 hours.

(N.A in ouPharmacy,Expectorant)

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.

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)

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.

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