teori dan konsep chronic relapsing brain disease

7/27/2019 TEORI DAN KONSEP CHRONIC RELAPSING BRAIN DISEASE

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TEORI DAN KONSEPCHRONIC RELAPSING

BRAIN DISEASEOleh:

Dr Izani Uzair bin Zubair

Ketua Penolong Pengarah(Perubatan)

Jabatan Kesihatan Negeri Pulau Pinang


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Addiction is a Brain Disease


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Brain Disease

Drug addiction is a brain disease

Every type of psychoactive drug has its ownindividual mechanism for changing how thebrain functions

Drug use changes the individual's brain andits functioning in critical ways

Leshner, 2001


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Addiction is a Brain Disease BECAUSE:

Using drugs over time changes brain structure

and function Some brain changes may persist after use

stops

Long-lasting brain changes effect cognitive functioning

emotional functioning


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Addiction is a brain disease

addicted brain is different from the non-addicted brain

Prolonged drug use causes pervasive changes in brain

function


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Essence of Addiction

Compulsive craving that overwhelms all

other motivations (drug use despite

negative and social consequences)

root cause of health and social problems


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Paradox of Addiction

Initially Voluntary


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Addictions Similarities withOther Brain Diseases

Some brain diseases are NOT simplybiological in nature and expression

Most have social/behavioral aspects

Examples:

Alzheimer's

Schizophrenia

Clinical Depression


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The Adult Brain,and how it works

An Adult brain

weighs about 3

pounds andhas billions of

cells

Neurons Glial cells


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The Brain Organ on thinking, behavior, homeostasis

Different Areas of the brain regulate

different functions Complex tasks are split up into specialized

areas

Damage to these areas leads to specificdeficits

Division of labor allows for Parallel

Processing


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Brain Region & Function Splits larger tasks into smaller ones

Component tasks are furtherbroken into sub component tasks

Driving

Seeing Hearing

Moving


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Understanding How the Brain Works


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Understanding How the Brain Works


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Function of Brain Regions Brainstem= basic function

Heart rate, breathing, digestion, sleep

Cerebellum =skilled repetitive

movements, balance

Limbic System=emotions & motivations

Diencephalon=sensory perception


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Function of Brain Regions Cerebral Cortex = thinking, perceiving,

producing language

Vision, hearing, touch, movement, smell, thinking& reasoning

Frontal Lobe = social behavior Limbic System

Uses memories, information about how the bodyis working and sensory input


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Function and Brain Regions


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Phineas Gage 1848 Railroad worker

Explosion- tamping rod

Rod entered brain

Temperament changes 20 years post accident

Correlated accident tobehavioral changes

Frontal lobe = socialbehavior


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Neurons, Brain Chemistry & Neurotransmission


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The Neuron

Basic signaling unit of brain Precise connections allow for

different actions

Neurons

Sensory receptors

Muscles


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The

Neuron

Cell Body

Nucleus

Metabolic center

Dendrites

Input from otherneurons

AxonCarry high speedmessages awayfrom neuron

Branches into

presynapticterminals


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The Synapse


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The Synapse


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N

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TheSynapse

End of axon

Typical neuron has 1000 synapses with other neurons

Intercellular space between neurons

Synaptic cleft


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Synapses are Dynamic Neurons can strengthen synaptic

connections

New synapses form (protein synthesis) Synapses can be lost

Responses to life experiences (and aging)

Cellular basis of learning


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Synaptic Transmission

Neurons communicate viaelectrical and chemical signals

Electrical signal converted to a

chemical signal aneurotransmitter

Electrical signal within a neuron is

an action potential Wave-like flow of ions (electrical

impulse) down axon

Transient depolarization of axon


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Synaptic Transmission At the axon terminal,

the electrical impulseleads to release of a

neurotransmitter Stored in vesicles

which fuse with theneuronal membrane

and release theircontents into the cleft


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Neurotransmittersdiffuse intointercellular space

Bind to receptors ondendrite of anothercell

Postsynaptic cell

Receptors arespecificDopamine receptorswill only binddopamine


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Synaptic Transmission Chemical binding of

transmitter withreceptor leads tochanges in the post-

synaptic cell May generate an action

potential

Post-synaptic cell may

use a differentneurotransmitter tocommunicate downstream


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Neurotransmission


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After binding,

neurotransmitters releases

from receptor and goes

back into the cleft

Removed by enzymes or

reuptake pump/ transporter

back into terminal

quick removal of transmittersallow for precise

communication between

neurons


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Types of Neurotransmitters

A neuron receives many many messages

from connecting neurons

Neurons response is the sum

Excitatory Transmitters

Lead to (generation of As and) stimulate

firing of post-synaptic neuron

Inhibitory Transmitters

Lead to decreased firing in post-synaptic

neuron


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Routes of Administration Inhale

Insuflate

Ingest

Inject

Enema

Contact Absorption (patch)


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Drug Ingestion


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ORAL

INHALING


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INHALING

7 to 10 Seconds INJECTING


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INJECTING

15 to 30 seconds- IV

3 to 5 minutes- skin popping

SNORTING


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SNORTING

3 to 5 minutes

O


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CONTACT


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Limbic System

Reward System

Nucleusaccumbens

Prefrontal

cortex Ventral

tegmental area


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Limbic System Link between higher cortical activity and the

lower systems that control emotional

behavior

Limbic Lobe

Deep lying structures

amygdala

hippocampus

mamillary bodies


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Limbic System Specialized brain areas for producing

and regulating PLEASURE

Ventral Tegmental Area

Nucleus Accumbens

Prefrontal Cortex

Areas of Limbic system amygdala,hippocampus, hypothalamus


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Limbic System Generates primitive emotional

responses to situations

Allows for SURVIVAL

Identify danger/ threats

Fear and aggression

Identify pleasurenatural rewards

Eating Sex

Social Interaction


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R

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r

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P

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t

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VTA and NA

Primitive brain stem and limbic areas

Activated by drugs of abuse Activation of these primitive areas can

OVERRIDE more evolved cortical areas


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Reward Pathway

Also the site of action for addictions

Drugs activate the pathway with force and

persistence not seen with natural rewards


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Drug Effects On Neurotransmission

Alcohol, heroin, nicotine excite the dopamine

neurons in the VTA to increase dopamine

release


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Drug Effects on Cell Increased CAMP levels

Activation of transcription factor CREB and

changes in gene expression

Changes in synapses, cell structure and function

The resulting intracellular changes appear to

be the molecular and cellular basis of

addiction (persistent behavioral

abnormalities)

Nestler Am J Addiction 2001; 201-217


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Drug Effects on Cell and Learning

Intracellular changes for addiction

the same as for learning

Both activities share intracellular

signaling cascades (cAMP) and

depend on activity of CREB


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Drug Effects on Cell and Learning Learning and addiction show similar

changes in neuron morphology

Similar changes at the level of thesynapse

Multiple similar changes in the

neuron Long term changes

Addiction is long termNestler 2001 Science 292 (5525) pp 2266-67


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Drug Effects on the Cell

Drugs of abuse all directly or indirectly increase dopaminebinding to post synaptic receptor with acute behavioral effects

Chronically, this increases cAMP levels and leads to a cascade ofchanged cell activity


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Other Chronic Drug Effects Cell Death

Neurons

dont grow

back Alcohol,

ecstasy, meth

Effectmemory,

mood,

learning


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Chronic Drug Effects

P i t t Eff t f D U


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Nature Video Cocaine Video

Front of Brain

Back of Brain

Amygdala

not lit upAmygdala

activated

Persistent Effects of Drug Use


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Brain Imaging PET

Brain Functioning

Radiolabeled glucose for levels of activity

Effects of Drugs

Distribution in body

Measure local concentration at binding

sites

Spatial Resolution of 4 mm


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Positron Emission Tomography (PET)

NIDA R h


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NIDA Research

Overall goal of NIDA research to: Reverse the brain changes that

underlie addiction

Roll back the loss of cognitive and

motor functions that occur Develop interventions to stop brain

damage, repair damage, and retrain

the brain

Restore brain function after it hasbeen changed by drug use


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PET Scan

Brighter red indicates higher levels of activity

(glucose utilization)


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Your Brain on Drugs

1-2 Min 3-4 5-6

6-7 7-8 8-9

9-10 10-20 20-30


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Your Brain After Drugs

Drugs Have


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g

Long-term

Consequences


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Stimulant Studies London et al. (2004)

PET images of brain activity

Patients in acute methamphetamine

withdrawal (4 to 7 days)

Patients

10 year history

4 grams per week

18 days of use out of 30


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Stimulant Studies

London et al. (2004) levels of depression and anxiety

measured

PET Scans Patient Report

brain- glucose metabolism-depressedmood, sadness, anxiety, and drugcraving

Becks Depression Inventory ratingsaveraged 9.5 for methamphetamine

patients and 1.1 for control

Examples of Brain Studies


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Examples of Brain Studies

Treatment Application

London et al. (2004)Treatment of Methamphetamine Users

Mood disorder symptoms maycreate an acute barrier totreatment formethamphetamine abusers


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Stimulant Studies


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Treatment Applications fromLondons Stimulant Studies

Implications for treatment

Expect clients to feel poorly

Treatment engagement strategies should focus on

helping patients to deal with negative emotional

states (Depression and Anxiety)

Avoid counseling techniques that are confrontational

Relapse potential is high because clients feel poorly

Be aware of clients turning to self medication

activities to relieve the negative feeling states


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Cues for Cocaine and Normal Pleasures

Activate Brain Sites Childress, 1999

Cues for Cocaine

Cocaine abusers may experience a

powerful urge to use when theyencounter environmental cues

associated with use

Limbic regions of the brain areactivated when watching cocaine-

related videosChildress, 1999

Persistent Effects of Drug


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Persistent Effects of Drug

As a result of intracellular changes, the

previously cocaine addicted brain has

persistently altered functioning (craving)

Environmental Cues


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Environmental Cues


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Implications for Treatment

Understand the importance environmentalcues play in initiating the craving process

Review program educational materials toensure that potential environmental cues fordrug use are eliminated

Normalize cue and craving responses forclients

Teach clients how to urge surf and to

identify potential environmental cues

Treatment Applications for ChildressCue-Induced Cocaine Craving Study

Recovery of Dopamine Transporters


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Recovery of Dopamine Transporters

Pet scan shows levels of dopamine transporters

Lower levels of dopamine transporters were associated with poorerperformance on tests of memory and motor skills

Impairments in motor skills and memory continued

Volkow, et al. 2001


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Poor Motor & Memory Performance

33 year old male- 80 days post detox

Low Severity- Parkinson Disease

transporter losses may not recover

Volkow, et al. 2001


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Simon, et al. 2002


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Simon, et al. 2002

Cognitive Effects of Stimulants

Help clients who are mandated into treatmentdeal with cognitive problems associatedcomprehension

Ensure that clients understand what counts as compliance with treatment

services

counselor recommendations

consequences for failure to comply

Give concrete, specific information

Develop methods to help clients remember

treatment recommendations or medications

Treatment Applications for Simon,


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Treatment Applications for Simon,

et al.s study

Treatment Implications:

Drugs impact on brain chemistry may

have permanent or long term effects

(impairment 2 years)

Extend length of treatment

Inform/educate client

Structure accessible services

Avoid changing service delivery times

Simplify client paperwork


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THANK YOU

teori dan konsep chronic relapsing brain disease

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