SlideShare uma empresa Scribd logo
1 de 41
Baixar para ler offline
DRUG ADDICTION 
 
Mohsin Aziz 1
BSc., Pharm.D, RPh. 
Mohsin Aziz 2
Definitions: 
 
 Drug Abuse: 
• Drug abuse is any recurrent use of drug that is illegal 
or causes harm to individual. 
• Using a drug as a habit 
• Use of a drug to an extent that it produces 
impairment of social, psychological or physiological 
functioning. 
Mohsin Aziz 3
Definitions: 
 
 Tolerance: 
Reduction in pharmacological effects on repeated 
administration of drug, requiring escalation of dose to 
maintain same effects. 
 Physical Dependence: 
The state of response to a drug whereby removal of 
the drug evokes unpleasant symptoms, usually the 
opposite of drug effects. 
Mohsin Aziz 4
Definitions: 
 
 Withdrawal Symptoms ( Abstinence Syndrome) : 
• Signs and symptoms that follows the abrupt 
discontinuation or reduction in the use of a 
substance or after blockage of the actions of a 
substance with antagonists. 
• Tend to be opposite to original effects of drug. 
• Evidence of physical or psychological dependence. 
Mohsin Aziz 5
Definitions: 
 
 Psychological Dependence: 
The state of response to a drug whereby the drug 
taker feels compelled to use the drug and suffers 
anxiety if doesn’t take drug. 
 Reinforcement: 
Refers to the capacity of drugs to produce Hedonic 
(pleasureable) effects that make user wish to take them 
again. (Reward of Drug) 
Mohsin Aziz 6
Definitions: 
 
 Drug Addicition : 
Drug addiction is a chronic, relapsing disorder in 
which compulsive drug-seeking and drug-taking 
behavior persists despite serious negative 
consequences. 
 The Stages of Addiction 
• Exposure 
• Compulsion 
• Loss of control 
Mohsin Aziz 7
Mohsin Aziz 8
How does a brain become 
addicted….??? 
 
• A person takes a drug of abuse. 
• Drug activates the same brain circuits as do behaviors 
linked to survival, such as eating, bonding and sex. 
• The drug causes a surge in levels of a brain chemical called 
dopamine, which results in feelings of pleasure. The brain 
remembers this pleasure and wants it repeated. 
• Just as food is linked to survival in day-to-day living, drugs 
begin to take on the same significance for the addict. The 
need to obtain and take drugs becomes more important 
than any other need, including truly vital behaviors like 
eating. The addict no longer seeks the drug for pleasure, but 
for relieving distress. 
Mohsin Aziz 9
How does a brain become 
addicted….??? 
 
 Acutely, addictive drugs are both 
• rewarding (i.e., interpreted by the brain as intrinsically 
positive) and 
• reinforcing (i.e.,behaviors associated with drug use tend 
to be repeated). 
• With repeated use, however, addictive drugs produce 
molecular changes that, within a vulnerable brain, 
promote continued drug-taking behavior in a manner that 
becomes increasingly difficult to control. The central 
feature of addiction is compulsive drug use—the loss of 
control over the apparently voluntary acts of drug 
seeking and drug taking. 
Mohsin Aziz 10
Why do some people become addict 
while others do not………??????????? 
 
Mohsin Aziz 11
Biochemical Mechanism 
Of Drug Addiction 
 
Mohsin Aziz 12
Where Drugs Act 
 
Mohsin Aziz 13
Mohsin Aziz 14
Medial Forebrain 
Bundle 
 
 • ventral tegmental area (VTA) 
 • (lateral) hypothalamus (LH) 
 • nucleus accumbens (NAc) 
 • frontal cortex (FC) - key portions 
 - prefrontal cortex (pfc) 
 - orbitofrontal cortex (ofc) 
Mohsin Aziz 15
Dopaminergic 
Mesolimbic Pathway 
 
 A prevailing view is that the primary brain circuits relevant to 
drug addiction (responsible for activation of neurochemical 
reward pathways) involve dopaminergic mesolimbic pathways. 
 The mesolimbic dopamine system extends from dopamine 
(DA)1 -containing cell bodies within the ventral tegmental area 
(VTA) in brainstem to the nucleus accumbens (NuAcc) (part of 
the basal ganglia), prefrontal cortex and amygdala. 
 The hypothesis is that many abused substances (except the 
benzodiazepines) enhance dopamine release in 
• nucleus accumbens or 
• pre- frontal cortex or both. 
(Ó 2000 Blackwell Science Ltd, Journal of Clinical Pharmacy and Therapeutics, 25.) 
Mohsin Aziz 16
Mohsin Aziz 17
Dopaminergic 
Mesolimbic Pathway 
 
 Cocaine, for example, The primary mechanism of 
action believed to be related to its misuse is the 
inhibition of the dopamine transporter, which is 
responsible for the reuptake of dopamine into the 
presynaptic nerve terminal. Inhibition of the 
dopamine transporter (DAT) increases the synaptic 
concentrations of dopamine, enabling more 
activation of DA receptors. 
Mohsin Aziz 18
Mohsin Aziz 19
Mohsin Aziz 20
Mohsin Aziz 21
 
Effects of Drugs on 
Dopamine Release 
Mohsin Aziz 22
1100 
1000 
900 
800 
700 
600 
500 
400 
300 
200 
100 
0 
Accumbens AMPHETAMINE 
0 1 2 3 4 5 hr 
Time After Amphetamine 
% of Basal Release 
DA 
DOPAC 
HVA 
250 
200 
150 
100 
0 
NICOTINE 
0 1 2 3 hr 
Time After Nicotine 
% of Basal Release 
Accumbens 
Caudate 
250 
200 
150 
100 
ETHANOL 
0 1 2 3 4hr 
Time After Ethanol 
% of Basal Release 
0.25 
0.5 
1 
2.5 
Accumbens 
0 
Dose (g/kg ip) 
Mohsin Aziz 23
 
Natural Rewards Elevate 
Dopamine Levels 
Mohsin Aziz 24
200 
150 
100 
50 
0 
FOOD 
0 60 120 180 
Time (min) 
% of Basal DA Output 
NAc shell 
Empty 
Box Feeding 
Source: Di Chiara et al. 
200 
150 
100 
DA Concentration (% Baseline) 
Scr 
SEX 
Mounts 
Intromissions 
Ejaculations 
15 
10 
5 
0 
Copulation Frequency 
Sample 
Number 
ScrScr 
BasFemale 1 Present 
Scr 
Female 2 Present 
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 
Source: Fiorino and Phillips 
Mohsin Aziz 25
Dopaminergic 
Mesolimbic Pathway 
 
 NEUROCHEMICAL REWARD PATHWAY 
• The mesolimbic dopamine system, including its 
projections to the nucleus accumbens, and local 
GABAergic afferents, has been most clearly 
associated with the habit-forming aspects of drugs of 
abuse. 
Mohsin Aziz 26
Dopaminergic 
Mesolimbic Pathway 
 
 ANTI-REWARD SYSTEMS 
• Negative reinforcement (in the form of dysphoric 
affective and physical withdrawal symptoms) plays 
an important. 
• Hence, cessation of drug-taking results in physical 
and affective motivation to take drug again and 
again. 
Mohsin Aziz 27
Dopaminergic 
Mesolimbic Pathway 
 
Effets of chronic Drug Use 
• Studies have showed that chronic administration of 
drugs of abuse, among many other changes, induces 
higher levels of tyrosine hydroxylase (TH), the rate-limiting 
enzyme in dopamine synthesis. 
• Chronic drug exposure causes: 
Mohsin Aziz 28
Dopaminergic 
Mesolimbic Pathway 
 
• decreased levels of neurofilament (NF) proteins 
(major structural determinants of neurons) 
• increased glial fibrillary acidic protein (GFAP), 
which are major structural determinants of glia 
within the VTA. 
• Together, these neuroadaptations identified in the 
VTA are suggestive of a state of neuronal injury 
• reductions in NF proteins in the VTA might result in 
reductions in the caliber of the neuronal processes 
and possibly an overall decrease in their size. 
Mohsin Aziz 29
Mohsin Aziz 30
 
Biochemical Mechanism 
of Drug Addiction 
Mohsin Aziz 31
Mohsin Aziz 32
Mechanism Of drug 
Addiction 
 
Since each addictive drug has a specific molecular target to 
activate mesolimbic system, 
Three classes can be distinguished: 
First Group,binds Gio-coupled 
receptors,eg.,Opioids,Canbinoids,LSD etc. 
Second group,binds to Ion 
Channels,eg.,Nicotine,Alcohol,BZD. 
Third group,binds to transporters of biogenic 
amines,eg.,Cocaine,amphetamine 
Mohsin Aziz 33
Mechanism Of drug 
Addiction 
 
The Common 
Signaling Pathway 
of All these drugs is: 
Mohsin Aziz 34
Mechanism Of drug 
Addiction 
 
Activation Of Dopamine receptors D1 D5 
Activation of G Protien G s 
Activation of Adenyl Cyclase 
AC converts ATP into cAMP 
Causes phosphorylation of cAMP dependent Protein Kinase A,DARPP-32 ( 32kDa-Dopamine 
and cAMP regulated Phosphoprotein) 
This phosphorylated DARPP-32 act as an inhibitor of Protein Phosphatase(dec. cAMP) such as 
protein phosphatase-1 and Calcineurin 
Mohsin Aziz 35
Mechanism Of drug 
Addiction 
 
Thus acting parallel to PK and Inc Phosphorylation 
An amplifying mechanism. 
On chronc administration these drugs inc, activity of AC in nAcc; 
Morphine,for example, dec. AC 
Dec. in AC leads to secondary rise in AC expression 
Inc. AC exp. Leads to tolerance 
On cessation of morphine excessive cAMP production occurs (withdrawal Symptoms) 
Mohsin Aziz 36
Mechanism Of drug 
Addiction 
 
Chronic treatment inc. amount of not only AC itself but also of other components of signaling 
pathways i.e. G proteins and various PKs. 
This inc. in cAMP leads to inc. in cAMP dep. PKs which control the activity of : 
Ion channels (making cells more excitable) 
Various Enzymes 
Transcription factors ( particularly cAMP response element-binding protein CREB is 
upregulated in nAcc) 
CREB plays Key role in var. cAMP sig. pathways. 
Mohsin Aziz 37
 
And After all these 
changes what 
Happens………???????? 
Mohsin Aziz 38
Mohsin Aziz 39
Mohsin Aziz 40
REFERENCES 
 
 H.P RANG, et al.RANG AND DALE’S Pharmacology.6th edition.Churchill 
livingstone.2007 
 Betram G. KATZUNG.Basic and Clinincal Pharmacology.10th edition.Mc Graw 
Hill.2007 
 Goodman & Gillman’s Manual of Pharmacology and Therapeautics.Laurence 
L.Brunton, Keith L.Parker edis.Mc Graw Hill.USA.2008 
 Jennifer Chao and Eric J. Nestler. MOLECULAR NEUROBIOLOGY OF DRUG 
ADDICTION. Department of Psychiatry and Center for Basic Neuroscience, The 
University of Texas,Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 
Texas.2004 
 Robinson TE, Berridge KC. 2003. Addiction.Annu. Rev. Psychol. 54:25–53 
 Koob GF, Le Moal M. 2001. Drug addiction,dysregulation of reward, and 
allostasis.Neuropsychopharmacology 24:97–129 
 Nestler EJ, Aghajanian GK. 1997. Molecular and cellular basis of addiction. Science 
 278:58–63 
 Nestler EJ. 2001. Molecular basis of longterm plasticity underlying addiction. Nat. 
 Rev. Neurosci. 2:119–28 
 Foote SL, Bloom FE, Aston-Jones G.1983. Nucleus locus ceruleus: new evidence of 
anatomical and physiological specificity. Physiol. Rev. 63:844–914 
Mohsin Aziz 41

Mais conteúdo relacionado

Mais procurados (20)

Drug addiction
Drug addictionDrug addiction
Drug addiction
 
Neurobiology of addiction,
Neurobiology of addiction,Neurobiology of addiction,
Neurobiology of addiction,
 
Drug Dependence & Abuse - Presentation by Akshay Anand
Drug Dependence & Abuse - Presentation by Akshay AnandDrug Dependence & Abuse - Presentation by Akshay Anand
Drug Dependence & Abuse - Presentation by Akshay Anand
 
Biology of schizophrenia
Biology of schizophreniaBiology of schizophrenia
Biology of schizophrenia
 
Drugs Of Abuse
Drugs Of AbuseDrugs Of Abuse
Drugs Of Abuse
 
Dopamine
DopamineDopamine
Dopamine
 
Drugs of Abuse: Benzodiazepines
Drugs of Abuse: BenzodiazepinesDrugs of Abuse: Benzodiazepines
Drugs of Abuse: Benzodiazepines
 
Opioids
OpioidsOpioids
Opioids
 
Drug dependence & Drug Abuse
Drug dependence & Drug AbuseDrug dependence & Drug Abuse
Drug dependence & Drug Abuse
 
Psychoactive drugs
Psychoactive drugsPsychoactive drugs
Psychoactive drugs
 
Drug abuse
Drug abuseDrug abuse
Drug abuse
 
Drug abuse
Drug abuseDrug abuse
Drug abuse
 
Pharmacology of dopamine
Pharmacology of dopaminePharmacology of dopamine
Pharmacology of dopamine
 
Drug addiction
Drug addictionDrug addiction
Drug addiction
 
Drugs & Society Chapters 7 & 8
Drugs & Society Chapters 7 & 8Drugs & Society Chapters 7 & 8
Drugs & Society Chapters 7 & 8
 
Dopamine
DopamineDopamine
Dopamine
 
Escaping the temptations of Drub abuse
Escaping the temptations of Drub abuseEscaping the temptations of Drub abuse
Escaping the temptations of Drub abuse
 
Drug Addictions
Drug AddictionsDrug Addictions
Drug Addictions
 
Neurobiology of addiction
Neurobiology of addictionNeurobiology of addiction
Neurobiology of addiction
 
Hormonal Explanation of Aggression
Hormonal Explanation of AggressionHormonal Explanation of Aggression
Hormonal Explanation of Aggression
 

Semelhante a Drug Addiction

Opioids
Opioids		Opioids
Opioids Khalid
 
Opioids Drugs
Opioids DrugsOpioids Drugs
Opioids DrugsKhalid
 
Drug addiction neurobiology
Drug addiction neurobiologyDrug addiction neurobiology
Drug addiction neurobiologySyed Shams
 
Antidepressants. Mood Stabilizers. Psychostimulants
Antidepressants. Mood Stabilizers. PsychostimulantsAntidepressants. Mood Stabilizers. Psychostimulants
Antidepressants. Mood Stabilizers. PsychostimulantsEneutron
 
ALL CHAPTERS OF PHARMACOLOGY.pptx
ALL CHAPTERS OF PHARMACOLOGY.pptxALL CHAPTERS OF PHARMACOLOGY.pptx
ALL CHAPTERS OF PHARMACOLOGY.pptxDrAbdikadirOsman1
 
The Pharmacological Intervention in Drug and Alcohol Addiction
The Pharmacological Intervention in Drug and Alcohol AddictionThe Pharmacological Intervention in Drug and Alcohol Addiction
The Pharmacological Intervention in Drug and Alcohol AddictionColleen Farrelly
 
General psychopharmacology
General psychopharmacologyGeneral psychopharmacology
General psychopharmacologySalman Kareem
 
Drug metabolism ppt
Drug metabolism pptDrug metabolism ppt
Drug metabolism pptSameera Sam
 
Drug metabolism ppt
Drug metabolism pptDrug metabolism ppt
Drug metabolism pptSameera Sam
 
Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...
Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...
Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...Shewta shetty
 
Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...
Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...
Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...Shewta shetty
 
Neurobiology of Opiate Addiction and Neural Circuitries Involved
Neurobiology of Opiate Addiction and Neural Circuitries InvolvedNeurobiology of Opiate Addiction and Neural Circuitries Involved
Neurobiology of Opiate Addiction and Neural Circuitries InvolvedCharles Mayer
 
Introduction of pharmacology.ppt
Introduction of pharmacology.pptIntroduction of pharmacology.ppt
Introduction of pharmacology.pptDr. Adanwali Hassan
 
principle of pharmacology
principle of pharmacologyprinciple of pharmacology
principle of pharmacologybahati_jr
 

Semelhante a Drug Addiction (20)

Reward system (1) (1) (1)
Reward system (1) (1) (1)Reward system (1) (1) (1)
Reward system (1) (1) (1)
 
Rewardsystem
RewardsystemRewardsystem
Rewardsystem
 
NEUROPHAMACOLOGY
NEUROPHAMACOLOGYNEUROPHAMACOLOGY
NEUROPHAMACOLOGY
 
Opioids
Opioids		Opioids
Opioids
 
Opioids Drugs
Opioids DrugsOpioids Drugs
Opioids Drugs
 
Drug addiction neurobiology
Drug addiction neurobiologyDrug addiction neurobiology
Drug addiction neurobiology
 
Pharmacovigila final 2
Pharmacovigila final 2Pharmacovigila final 2
Pharmacovigila final 2
 
Antidepressants. Mood Stabilizers. Psychostimulants
Antidepressants. Mood Stabilizers. PsychostimulantsAntidepressants. Mood Stabilizers. Psychostimulants
Antidepressants. Mood Stabilizers. Psychostimulants
 
ALL CHAPTERS OF PHARMACOLOGY.pptx
ALL CHAPTERS OF PHARMACOLOGY.pptxALL CHAPTERS OF PHARMACOLOGY.pptx
ALL CHAPTERS OF PHARMACOLOGY.pptx
 
The Pharmacological Intervention in Drug and Alcohol Addiction
The Pharmacological Intervention in Drug and Alcohol AddictionThe Pharmacological Intervention in Drug and Alcohol Addiction
The Pharmacological Intervention in Drug and Alcohol Addiction
 
pharmacology
pharmacologypharmacology
pharmacology
 
General psychopharmacology
General psychopharmacologyGeneral psychopharmacology
General psychopharmacology
 
Drug metabolism ppt
Drug metabolism pptDrug metabolism ppt
Drug metabolism ppt
 
Drug metabolism ppt
Drug metabolism pptDrug metabolism ppt
Drug metabolism ppt
 
opioid.pptx
opioid.pptxopioid.pptx
opioid.pptx
 
Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...
Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...
Effective treatment for drug addiction in Mindheal Homeopathy clinic ,Chembur...
 
Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...
Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...
Homeopathic Doctor - Dr. Anita Salunke homeopathic clinic for Drug Addiction ...
 
Neurobiology of Opiate Addiction and Neural Circuitries Involved
Neurobiology of Opiate Addiction and Neural Circuitries InvolvedNeurobiology of Opiate Addiction and Neural Circuitries Involved
Neurobiology of Opiate Addiction and Neural Circuitries Involved
 
Introduction of pharmacology.ppt
Introduction of pharmacology.pptIntroduction of pharmacology.ppt
Introduction of pharmacology.ppt
 
principle of pharmacology
principle of pharmacologyprinciple of pharmacology
principle of pharmacology
 

Último

Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024EwoutSteyerberg1
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxMAsifAhmad
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...Shubhanshu Gaurav
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptxWINCY THIRUMURUGAN
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionkrishnareddy157915
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)kishan singh tomar
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyMedicoseAcademics
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.kishan singh tomar
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project reportNARMADAPETROLEUMGAS
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsMedicoseAcademics
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyZurück zum Ursprung
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxNaveenkumar267201
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Vaikunthan Rajaratnam
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.pptRamDBawankar1
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondSujoy Dasgupta
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu Medical University
 

Último (20)

GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
 
Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024Trustworthiness of AI based predictions Aachen 2024
Trustworthiness of AI based predictions Aachen 2024
 
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptxDNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
DNA nucleotides Blast in NCBI and Phylogeny using MEGA Xi.pptx
 
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
FDMA FLAP - The first dorsal metacarpal artery (FDMA) flap is used mainly for...
 
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptxANATOMICAL FAETURES OF BONES  FOR NURSING STUDENTS .pptx
ANATOMICAL FAETURES OF BONES FOR NURSING STUDENTS .pptx
 
American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...American College of physicians ACP high value care recommendations in rheumat...
American College of physicians ACP high value care recommendations in rheumat...
 
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...Biologic therapy ice breaking in rheumatology, Case based approach with appli...
Biologic therapy ice breaking in rheumatology, Case based approach with appli...
 
EXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung functionEXERCISE PERFORMANCE.pptx, Lung function
EXERCISE PERFORMANCE.pptx, Lung function
 
High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)High-Performance Thin-Layer Chromatography (HPTLC)
High-Performance Thin-Layer Chromatography (HPTLC)
 
Female Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before PregnancyFemale Reproductive Physiology Before Pregnancy
Female Reproductive Physiology Before Pregnancy
 
Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...Rheumatoid arthritis Part 1, case based approach with application of the late...
Rheumatoid arthritis Part 1, case based approach with application of the late...
 
Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.Different drug regularity bodies in different countries.
Different drug regularity bodies in different countries.
 
blood bank management system project report
blood bank management system project reportblood bank management system project report
blood bank management system project report
 
AUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functionsAUTONOMIC NERVOUS SYSTEM organization and functions
AUTONOMIC NERVOUS SYSTEM organization and functions
 
How to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturallyHow to cure cirrhosis and chronic hepatitis naturally
How to cure cirrhosis and chronic hepatitis naturally
 
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptxBreast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
Breast cancer -ONCO IN MEDICAL AND SURGICAL NURSING.pptx
 
Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.Generative AI in Health Care a scoping review and a persoanl experience.
Generative AI in Health Care a scoping review and a persoanl experience.
 
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D.  Bawankar.pptPharmacokinetic Models by Dr. Ram D.  Bawankar.ppt
Pharmacokinetic Models by Dr. Ram D. Bawankar.ppt
 
Male Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and BeyondMale Infertility, Antioxidants and Beyond
Male Infertility, Antioxidants and Beyond
 
historyofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusanguhistoryofpsychiatryinindia. Senthil Thirusangu
historyofpsychiatryinindia. Senthil Thirusangu
 

Drug Addiction

  • 1. DRUG ADDICTION  Mohsin Aziz 1
  • 2. BSc., Pharm.D, RPh. Mohsin Aziz 2
  • 3. Definitions:   Drug Abuse: • Drug abuse is any recurrent use of drug that is illegal or causes harm to individual. • Using a drug as a habit • Use of a drug to an extent that it produces impairment of social, psychological or physiological functioning. Mohsin Aziz 3
  • 4. Definitions:   Tolerance: Reduction in pharmacological effects on repeated administration of drug, requiring escalation of dose to maintain same effects.  Physical Dependence: The state of response to a drug whereby removal of the drug evokes unpleasant symptoms, usually the opposite of drug effects. Mohsin Aziz 4
  • 5. Definitions:   Withdrawal Symptoms ( Abstinence Syndrome) : • Signs and symptoms that follows the abrupt discontinuation or reduction in the use of a substance or after blockage of the actions of a substance with antagonists. • Tend to be opposite to original effects of drug. • Evidence of physical or psychological dependence. Mohsin Aziz 5
  • 6. Definitions:   Psychological Dependence: The state of response to a drug whereby the drug taker feels compelled to use the drug and suffers anxiety if doesn’t take drug.  Reinforcement: Refers to the capacity of drugs to produce Hedonic (pleasureable) effects that make user wish to take them again. (Reward of Drug) Mohsin Aziz 6
  • 7. Definitions:   Drug Addicition : Drug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences.  The Stages of Addiction • Exposure • Compulsion • Loss of control Mohsin Aziz 7
  • 9. How does a brain become addicted….???  • A person takes a drug of abuse. • Drug activates the same brain circuits as do behaviors linked to survival, such as eating, bonding and sex. • The drug causes a surge in levels of a brain chemical called dopamine, which results in feelings of pleasure. The brain remembers this pleasure and wants it repeated. • Just as food is linked to survival in day-to-day living, drugs begin to take on the same significance for the addict. The need to obtain and take drugs becomes more important than any other need, including truly vital behaviors like eating. The addict no longer seeks the drug for pleasure, but for relieving distress. Mohsin Aziz 9
  • 10. How does a brain become addicted….???   Acutely, addictive drugs are both • rewarding (i.e., interpreted by the brain as intrinsically positive) and • reinforcing (i.e.,behaviors associated with drug use tend to be repeated). • With repeated use, however, addictive drugs produce molecular changes that, within a vulnerable brain, promote continued drug-taking behavior in a manner that becomes increasingly difficult to control. The central feature of addiction is compulsive drug use—the loss of control over the apparently voluntary acts of drug seeking and drug taking. Mohsin Aziz 10
  • 11. Why do some people become addict while others do not………???????????  Mohsin Aziz 11
  • 12. Biochemical Mechanism Of Drug Addiction  Mohsin Aziz 12
  • 13. Where Drugs Act  Mohsin Aziz 13
  • 15. Medial Forebrain Bundle   • ventral tegmental area (VTA)  • (lateral) hypothalamus (LH)  • nucleus accumbens (NAc)  • frontal cortex (FC) - key portions  - prefrontal cortex (pfc)  - orbitofrontal cortex (ofc) Mohsin Aziz 15
  • 16. Dopaminergic Mesolimbic Pathway   A prevailing view is that the primary brain circuits relevant to drug addiction (responsible for activation of neurochemical reward pathways) involve dopaminergic mesolimbic pathways.  The mesolimbic dopamine system extends from dopamine (DA)1 -containing cell bodies within the ventral tegmental area (VTA) in brainstem to the nucleus accumbens (NuAcc) (part of the basal ganglia), prefrontal cortex and amygdala.  The hypothesis is that many abused substances (except the benzodiazepines) enhance dopamine release in • nucleus accumbens or • pre- frontal cortex or both. (Ó 2000 Blackwell Science Ltd, Journal of Clinical Pharmacy and Therapeutics, 25.) Mohsin Aziz 16
  • 18. Dopaminergic Mesolimbic Pathway   Cocaine, for example, The primary mechanism of action believed to be related to its misuse is the inhibition of the dopamine transporter, which is responsible for the reuptake of dopamine into the presynaptic nerve terminal. Inhibition of the dopamine transporter (DAT) increases the synaptic concentrations of dopamine, enabling more activation of DA receptors. Mohsin Aziz 18
  • 22.  Effects of Drugs on Dopamine Release Mohsin Aziz 22
  • 23. 1100 1000 900 800 700 600 500 400 300 200 100 0 Accumbens AMPHETAMINE 0 1 2 3 4 5 hr Time After Amphetamine % of Basal Release DA DOPAC HVA 250 200 150 100 0 NICOTINE 0 1 2 3 hr Time After Nicotine % of Basal Release Accumbens Caudate 250 200 150 100 ETHANOL 0 1 2 3 4hr Time After Ethanol % of Basal Release 0.25 0.5 1 2.5 Accumbens 0 Dose (g/kg ip) Mohsin Aziz 23
  • 24.  Natural Rewards Elevate Dopamine Levels Mohsin Aziz 24
  • 25. 200 150 100 50 0 FOOD 0 60 120 180 Time (min) % of Basal DA Output NAc shell Empty Box Feeding Source: Di Chiara et al. 200 150 100 DA Concentration (% Baseline) Scr SEX Mounts Intromissions Ejaculations 15 10 5 0 Copulation Frequency Sample Number ScrScr BasFemale 1 Present Scr Female 2 Present 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Source: Fiorino and Phillips Mohsin Aziz 25
  • 26. Dopaminergic Mesolimbic Pathway   NEUROCHEMICAL REWARD PATHWAY • The mesolimbic dopamine system, including its projections to the nucleus accumbens, and local GABAergic afferents, has been most clearly associated with the habit-forming aspects of drugs of abuse. Mohsin Aziz 26
  • 27. Dopaminergic Mesolimbic Pathway   ANTI-REWARD SYSTEMS • Negative reinforcement (in the form of dysphoric affective and physical withdrawal symptoms) plays an important. • Hence, cessation of drug-taking results in physical and affective motivation to take drug again and again. Mohsin Aziz 27
  • 28. Dopaminergic Mesolimbic Pathway  Effets of chronic Drug Use • Studies have showed that chronic administration of drugs of abuse, among many other changes, induces higher levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. • Chronic drug exposure causes: Mohsin Aziz 28
  • 29. Dopaminergic Mesolimbic Pathway  • decreased levels of neurofilament (NF) proteins (major structural determinants of neurons) • increased glial fibrillary acidic protein (GFAP), which are major structural determinants of glia within the VTA. • Together, these neuroadaptations identified in the VTA are suggestive of a state of neuronal injury • reductions in NF proteins in the VTA might result in reductions in the caliber of the neuronal processes and possibly an overall decrease in their size. Mohsin Aziz 29
  • 31.  Biochemical Mechanism of Drug Addiction Mohsin Aziz 31
  • 33. Mechanism Of drug Addiction  Since each addictive drug has a specific molecular target to activate mesolimbic system, Three classes can be distinguished: First Group,binds Gio-coupled receptors,eg.,Opioids,Canbinoids,LSD etc. Second group,binds to Ion Channels,eg.,Nicotine,Alcohol,BZD. Third group,binds to transporters of biogenic amines,eg.,Cocaine,amphetamine Mohsin Aziz 33
  • 34. Mechanism Of drug Addiction  The Common Signaling Pathway of All these drugs is: Mohsin Aziz 34
  • 35. Mechanism Of drug Addiction  Activation Of Dopamine receptors D1 D5 Activation of G Protien G s Activation of Adenyl Cyclase AC converts ATP into cAMP Causes phosphorylation of cAMP dependent Protein Kinase A,DARPP-32 ( 32kDa-Dopamine and cAMP regulated Phosphoprotein) This phosphorylated DARPP-32 act as an inhibitor of Protein Phosphatase(dec. cAMP) such as protein phosphatase-1 and Calcineurin Mohsin Aziz 35
  • 36. Mechanism Of drug Addiction  Thus acting parallel to PK and Inc Phosphorylation An amplifying mechanism. On chronc administration these drugs inc, activity of AC in nAcc; Morphine,for example, dec. AC Dec. in AC leads to secondary rise in AC expression Inc. AC exp. Leads to tolerance On cessation of morphine excessive cAMP production occurs (withdrawal Symptoms) Mohsin Aziz 36
  • 37. Mechanism Of drug Addiction  Chronic treatment inc. amount of not only AC itself but also of other components of signaling pathways i.e. G proteins and various PKs. This inc. in cAMP leads to inc. in cAMP dep. PKs which control the activity of : Ion channels (making cells more excitable) Various Enzymes Transcription factors ( particularly cAMP response element-binding protein CREB is upregulated in nAcc) CREB plays Key role in var. cAMP sig. pathways. Mohsin Aziz 37
  • 38.  And After all these changes what Happens………???????? Mohsin Aziz 38
  • 41. REFERENCES   H.P RANG, et al.RANG AND DALE’S Pharmacology.6th edition.Churchill livingstone.2007  Betram G. KATZUNG.Basic and Clinincal Pharmacology.10th edition.Mc Graw Hill.2007  Goodman & Gillman’s Manual of Pharmacology and Therapeautics.Laurence L.Brunton, Keith L.Parker edis.Mc Graw Hill.USA.2008  Jennifer Chao and Eric J. Nestler. MOLECULAR NEUROBIOLOGY OF DRUG ADDICTION. Department of Psychiatry and Center for Basic Neuroscience, The University of Texas,Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas.2004  Robinson TE, Berridge KC. 2003. Addiction.Annu. Rev. Psychol. 54:25–53  Koob GF, Le Moal M. 2001. Drug addiction,dysregulation of reward, and allostasis.Neuropsychopharmacology 24:97–129  Nestler EJ, Aghajanian GK. 1997. Molecular and cellular basis of addiction. Science  278:58–63  Nestler EJ. 2001. Molecular basis of longterm plasticity underlying addiction. Nat.  Rev. Neurosci. 2:119–28  Foote SL, Bloom FE, Aston-Jones G.1983. Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol. Rev. 63:844–914 Mohsin Aziz 41

Notas do Editor

  1. For example: activation of mew receptors by an agonist causes inhibition of release of norepinephrine in Locus Cerelous(in limbic system).to overcome this inhibition Nepi synthesis increases,n during wuthdrawal when agonist is absent there is an excessive secretion of nEpi in LC n causes symptoms…such as Diarhea,nausea,vomiting,insomnia etc.