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A SEMINAR ON
      THE PHYSIOLOGY OF DRUG
             ADDICTION




BY,
 DAWN V TOMY. (M.PHARM)
 RVS COLLEGE OF PHARMACEUTICAL SCIENCES, SULUR
 COIMBATORE                                      1
INTRODUCTION TO DRUGS

WHO DEFINITION “A drug is any
substance or product that is used or
intended to be used to modify or explore
physiological systems or pathological
states for the benefit of the patient.



                                       2
DRUGS OF ABUSE
SF




                      3
NERVOUS SYSTEM
1.CENTRAL NERVOUS SYSTEM.

2.PERIPHERAL              NERVOUS
  SYSTEM.
  A. AUTONOMIC NERVOUS SYSTEM.
     i. SYMPATHETIC SYSTEM.
     ii. PARASYMPATHETIC SYSTEM.
  B. SOMATIC NERVOUS SYSTEM.
                                   4
5
NEURONS
Neurons are the basic unit of nervous system.




                                                6
7
NEUROTRANSMITTERS
EXCITATORY TRANSMITTERS.
GLUTAMATE, ASPARTATE.
INHIBITORY TRANSMITTERS.
GABA, GLYCINE.
OTHERS.
NORADRENALINE, ADRENALINE, DOPAMINE, SEROTONIN,
ACTYLCHOLINE, HISTAMINE, ENDOCANNOBINOIDS -
ENDOGENOUS OPIOID PEPTIDES - ENKEPHALINS,
ENDORPHINS, DYNORPHINS.


                                              8
RECEPTORS




            9
10
DRUGS ON RECEPTORS




                     11
SOME TERMINOLOGIES
• Addiction [Substance abuse] = Psychological +
  Physiological dependence
• Psychological = compulsive drug seeking, craving
• Physiological = symptoms and signs opposite to
  drug.
• Tolerance.



                                                12
SOME TERMINOLOGIES
Reinforcement: Tendency of a pleasure-
 producing drug to lead to repeated self
 administration
Withdrawal- Drug is suddenly stopped
 develop a withdrawal syndrome
 characterized by craving, dysphoria,
 signs of sympathetic overactivity.
Rebound - Drug- suddenly stopped— their
 symptoms come back in an exaggerated
 fashion.
                                      13
ADDICTION
• Addiction is a state in which a person engages in
  a compulsive behavior, even when faced with
  negative consequences.
• The behavior is rewarded and reinforced via the
  reward pathway.
• A major feature of addiction is the loss of control
  in limiting intake of the substance or behavior.
• Addiction is a chronic, relapsing disease resulting
  from fundamental changes in the brain.

                                                    14
YOUR BRAIN ON DRUGS

• All addictive drugs produce their effects by
  altering the synaptic activity.




                                                 15
16
DOPAMINE IS THE LINK IN ADDICTION
• Addictive drugs are biochemically quite
  different
  – Activate different neurotransmitter systems
  – Produce different psychoactive effects
  – Heroin acts on the opiate system
  – Nicotine acts on the cholinergic system
  – Cocaine acts on dopaminergic & noradrenergic
    systems
• All either stimulate dopamine release (heroin,
  nicotine) or enhance dopamine action
  (cocaine) in the nucleus accumbens.
                                                   17
THE REWARD PATHWAY




                     18
THE REWARD PATHWAY
• The reward pathway is in the limbic system
  consisting of the nucleus accumbens, ventral
  tegmental area (VTA) and the prefrontal cortex.
• The neurons of the VTA contain dopamine
  which is released into the nucleus accumbens
  and prefrontal cortex in response to natural or
  artificial reward stimuli.
• Stimulation of the reward pathway produces
  highly pleasurable sensations, providing positive
  reinforcement which promotes further drug use.
                                                  19
TYPES OF REWARD SYSTEMS
• Reward system is of 2 types.
    1. Natural reward system.
    2. Artificial reward system.

• “NATURAL” rewarding stimulus (e.g., food, water, sex,
  nurture) or “ARTIFICIAL” rewarding stimulus (e.g.,
  drugs), information travels from the VTA to the nucleus
  accumbens and then up to the prefrontal cortex.

• VTA contain dopamine which is released in
  the nucleus accumbens and in the prefrontal
  cortex.                                 20
21
DRUGS ACT IN DIFFERENT
   PARTS OF THE PATHWAY
• Heroin & nicotine act on the VTA.
  – These dopaminergic neurons have both
    opiate and nicotinic acetylcholine receptors.
• Cocaine acts on the nucleus accumbens.
  – The nucleus accumbens is a target of the
    ascending dopaminergic axons in the
    forebrain.

                                              22
Alcohol
Decreases the actions of the
excitatory NMDA receptor
complex, i.e., it diminishes
excitation.
•Enhances G B i nhi bi t i on.
             AA
•R educes gl ut am e exci t at i on.
                  at
•Enhances euphor i c ef f ect s by
r el easi ng O at es and
              pi
endocannabi noi ds, t her eby
m at i ng i t s "hi gh."
  edi                                  23
DRUG ABUSE AND ADDICTION

SELF ABUSE: REWARD PATHWAY.
ADDICTION: CHANGES IN THE
NEUROBIOLOGY OF THE BRAIN ON
REPEATED ADMINISTRATION.


                            24
THE MESOLIMBIC DOPAMINERGIC REWARD PATHWAY




                                        25
DRUG TOLERANCE
• When a substance is used repeatedly over
  time, tolerance may develop.
• The brain adjusts its chemistry to offset the
  effects of the drug and tolerance develops.
• As tolerance develops, more of the drug is
  needed to produce the same effects.



                                                  26
SUBSTANCE DEPENDENCE
• Substance dependence develops when
  neurons adapt to repeated drug use and only
  function normally in the presence of the drug.
• When dependency develops, the brain has
  become dependent upon the substance to
  function.
• Without the substance the user experiences
  withdrawal and intense cravings for the
  substance.

                                               27
REWARD DEFICIENCY
• Prolonged drug use causes the dopamine
  neurons in the reward pathway to cease
  functioning.
• This state of dopamine deficiency causes the
  user to experience chronic feelings of anxiety,
  depression and an inability to just feel good.
• The person can only feel normal when under the
  influence of the drug.

                                               28
ADDICTION VS. DEPENDENCE
• It is possible to be dependent on a drug without
  being addicted. Although, if one is addicted
  they are most likely also dependent.
• For example; A terminal cancer patient being
  treated with morphine for pain will experience
  withdrawal if the drug is stopped, but they are
  not a compulsive user of the drug therefore
  they are not addicted.

                                                 29
30

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Physiology of drug addiction

  • 1. A SEMINAR ON THE PHYSIOLOGY OF DRUG ADDICTION BY, DAWN V TOMY. (M.PHARM) RVS COLLEGE OF PHARMACEUTICAL SCIENCES, SULUR COIMBATORE 1
  • 2. INTRODUCTION TO DRUGS WHO DEFINITION “A drug is any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the patient. 2
  • 4. NERVOUS SYSTEM 1.CENTRAL NERVOUS SYSTEM. 2.PERIPHERAL NERVOUS SYSTEM. A. AUTONOMIC NERVOUS SYSTEM. i. SYMPATHETIC SYSTEM. ii. PARASYMPATHETIC SYSTEM. B. SOMATIC NERVOUS SYSTEM. 4
  • 5. 5
  • 6. NEURONS Neurons are the basic unit of nervous system. 6
  • 7. 7
  • 8. NEUROTRANSMITTERS EXCITATORY TRANSMITTERS. GLUTAMATE, ASPARTATE. INHIBITORY TRANSMITTERS. GABA, GLYCINE. OTHERS. NORADRENALINE, ADRENALINE, DOPAMINE, SEROTONIN, ACTYLCHOLINE, HISTAMINE, ENDOCANNOBINOIDS - ENDOGENOUS OPIOID PEPTIDES - ENKEPHALINS, ENDORPHINS, DYNORPHINS. 8
  • 10. 10
  • 12. SOME TERMINOLOGIES • Addiction [Substance abuse] = Psychological + Physiological dependence • Psychological = compulsive drug seeking, craving • Physiological = symptoms and signs opposite to drug. • Tolerance. 12
  • 13. SOME TERMINOLOGIES Reinforcement: Tendency of a pleasure- producing drug to lead to repeated self administration Withdrawal- Drug is suddenly stopped develop a withdrawal syndrome characterized by craving, dysphoria, signs of sympathetic overactivity. Rebound - Drug- suddenly stopped— their symptoms come back in an exaggerated fashion. 13
  • 14. ADDICTION • Addiction is a state in which a person engages in a compulsive behavior, even when faced with negative consequences. • The behavior is rewarded and reinforced via the reward pathway. • A major feature of addiction is the loss of control in limiting intake of the substance or behavior. • Addiction is a chronic, relapsing disease resulting from fundamental changes in the brain. 14
  • 15. YOUR BRAIN ON DRUGS • All addictive drugs produce their effects by altering the synaptic activity. 15
  • 16. 16
  • 17. DOPAMINE IS THE LINK IN ADDICTION • Addictive drugs are biochemically quite different – Activate different neurotransmitter systems – Produce different psychoactive effects – Heroin acts on the opiate system – Nicotine acts on the cholinergic system – Cocaine acts on dopaminergic & noradrenergic systems • All either stimulate dopamine release (heroin, nicotine) or enhance dopamine action (cocaine) in the nucleus accumbens. 17
  • 19. THE REWARD PATHWAY • The reward pathway is in the limbic system consisting of the nucleus accumbens, ventral tegmental area (VTA) and the prefrontal cortex. • The neurons of the VTA contain dopamine which is released into the nucleus accumbens and prefrontal cortex in response to natural or artificial reward stimuli. • Stimulation of the reward pathway produces highly pleasurable sensations, providing positive reinforcement which promotes further drug use. 19
  • 20. TYPES OF REWARD SYSTEMS • Reward system is of 2 types. 1. Natural reward system. 2. Artificial reward system. • “NATURAL” rewarding stimulus (e.g., food, water, sex, nurture) or “ARTIFICIAL” rewarding stimulus (e.g., drugs), information travels from the VTA to the nucleus accumbens and then up to the prefrontal cortex. • VTA contain dopamine which is released in the nucleus accumbens and in the prefrontal cortex. 20
  • 21. 21
  • 22. DRUGS ACT IN DIFFERENT PARTS OF THE PATHWAY • Heroin & nicotine act on the VTA. – These dopaminergic neurons have both opiate and nicotinic acetylcholine receptors. • Cocaine acts on the nucleus accumbens. – The nucleus accumbens is a target of the ascending dopaminergic axons in the forebrain. 22
  • 23. Alcohol Decreases the actions of the excitatory NMDA receptor complex, i.e., it diminishes excitation. •Enhances G B i nhi bi t i on. AA •R educes gl ut am e exci t at i on. at •Enhances euphor i c ef f ect s by r el easi ng O at es and pi endocannabi noi ds, t her eby m at i ng i t s "hi gh." edi 23
  • 24. DRUG ABUSE AND ADDICTION SELF ABUSE: REWARD PATHWAY. ADDICTION: CHANGES IN THE NEUROBIOLOGY OF THE BRAIN ON REPEATED ADMINISTRATION. 24
  • 25. THE MESOLIMBIC DOPAMINERGIC REWARD PATHWAY 25
  • 26. DRUG TOLERANCE • When a substance is used repeatedly over time, tolerance may develop. • The brain adjusts its chemistry to offset the effects of the drug and tolerance develops. • As tolerance develops, more of the drug is needed to produce the same effects. 26
  • 27. SUBSTANCE DEPENDENCE • Substance dependence develops when neurons adapt to repeated drug use and only function normally in the presence of the drug. • When dependency develops, the brain has become dependent upon the substance to function. • Without the substance the user experiences withdrawal and intense cravings for the substance. 27
  • 28. REWARD DEFICIENCY • Prolonged drug use causes the dopamine neurons in the reward pathway to cease functioning. • This state of dopamine deficiency causes the user to experience chronic feelings of anxiety, depression and an inability to just feel good. • The person can only feel normal when under the influence of the drug. 28
  • 29. ADDICTION VS. DEPENDENCE • It is possible to be dependent on a drug without being addicted. Although, if one is addicted they are most likely also dependent. • For example; A terminal cancer patient being treated with morphine for pain will experience withdrawal if the drug is stopped, but they are not a compulsive user of the drug therefore they are not addicted. 29
  • 30. 30

Editor's Notes

  1. THE SCIENCE THAT DEALS WITH THE ADDICTION TO THE DRUGS. PHYSIOLOGY IS A BRANCH OF MEDICAL SCIENCE THAT DEALS WITH HEALTHY FUNCTIONING OF DIFFERENT ORGANS AND THE CHANGES THAT THE WHOLE BODY UNDERGOES IN THE COURSE OF ITS ACTIVITIES. HOW A MAN GET ADDICTED TO DRUGS?
  2. INVESTIGATIVE: ANGIOGRAPHY, ENDOSCOPY, COLONOSCOPY…. PHYSIOLOGICAL: MENTAL CONDITION, PAIN, HORMONAL IMBALANCE, NUTRIENTS… PATHOLOGICAL: ANTIBIOTICS, ANTICANCER…, ELIXER: DRUG IS ALWAYS A MEDICINE IN APPROPRIATE DOSE.
  3. GENERAL DRUGS THAT ARE BEING ABUSED ARE 1. ALCOHOL, 2. SMOKING NICOTINE, 3. TEA AND COFFEE, 4. NARCOTIC DRUGS LIKE MORPHINE, CODEINE, PETHADINE, FENTANYL…. AND 5. BARBITURATES AND BENZODIAZEPINES. SELF ABUSE: IT’S A STATE IN WHICH A PERSON ENGAGES IN A COMPULSIVE BEHAVIOUR FOR PLEASURE, EVEN WHEN FACED WITH NEGATIVE CONSEQUENCES . REPEATED ADMINISTRATION OF DRUGS OF DEPENEDENCE MAKES A PERSON ADDICTED TO THAT DRUG; IN CERTAIN CASES A SINGLE DOSE OF NARCOTIC DRUGS MAKES ONE ADDICTED TO THAT DRUG. WHY? DUE TO THE CHANGES IN THE NEUROPHYSIOLOGY OF BRAIN.
  4. ELECTRIC CIRCUIT:CNS: BRAIN AND SPINAL CORD, ANS: INVOLUNTERY FOR HOMEOSTASIS, SNS: FOR VOLUNTERY ACTIONS (SKELETAL MUSCLES).
  5. WIRES
  6. TRANSMITTERS: TRANSPORTERS, A BRIDGE. NEUROBIOLOGY: HOMEOSTASIS. CHEMICAL BALANCE.
  7. TYPES OF RECEPTORS: ION CHANNELS, G-PROTEIN COUPLED, ENZYME, NUCLEUS. LOCK AND KEY: ALCOHOL ALSO ACTS THROUGH OPIATERECEPTORS AND OTHER INHIBIORY RECEPTORS RESULTING IN INITIAL EXCITATION FOLLOWED BY DEPRESSION.
  8. OPIOD RECEPTORS OF THE BRAIN (ENDORPHINS) FOR PAIN REGULATION.
  9. PHYSIOLOGICAL EG: COFFEE AND TEA: HEAD ACHE, DEPRESSION, NAUSEA. TOLERANCE: METABOLISING ENZYMES: EG ALCOHOL DEHYDROGENASE. DISUFIRAM-ALCOHOL ACCUMULATES: UNPLEASANT SYMPTOMS: NEGATIVE FEEDBACK MECHANISM: DEVELOPS AVERSION.
  10. EG. BZDP FOR PANIC ATTACKS SUDDENLY STOP PANIC ATTACK [REBOUND PANIC ATTACK].
  11. ALCOHOL DEHYDROGENASE.
  12. ADDICTION: ALCOHOL LONG TERM USE RESULTS IN ADDICTION DUE TO ENDORPHINS. OTHER DRUGS DIRECTLY ACTS ON REWARD PATHWAY.
  13. FEEDBACK: POSITIVE AND NEGATIVE. EG: A CHILD.
  14. ALCOHOLS: THROUGH ENDORPHINS.
  15. NALTREXONE BLOCKS OPIATE RECEPTORSDECREASES CRAVING -INCREASES ABSTINENCE RATES.IF ONE DRINKS WHEN TAKING NALTREXONE, THE OPIATES RELEASED DO NOT LEAD TO PLEASURE, SO WHY BOTHER DRINKING?
  16. SELF ABUSE: REWARD PATHWAY. ADDICTION: CHANGES IN THE NEUROBIOLOGY OF THE BRAIN ON REPEATED ADMINISTRATION.
  17. TOLERENCE TO ALCOHOL DUE TO ALCOHOL DEHYDROGENASE ENZYME
  18. DEPENDENCE: WITHDRAWL SYMPTOMS. ADDICTION: COMPULSION.