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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

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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.

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DRUGS OF ABUSESF

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NERVOUS SYSTEM1.CENTRAL NERVOUS

SYSTEM.

2.PERIPHERAL NERVOUS SYSTEM.

A. AUTONOMIC NERVOUS SYSTEM.i. SYMPATHETIC SYSTEM.ii. PARASYMPATHETIC SYSTEM.

B. SOMATIC NERVOUS SYSTEM.

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NEURONSNeurons are the basic unit of nervous system.

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

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RECEPTORS

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DRUGS ON RECEPTORS

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SOME TERMINOLOGIES

• Addiction [Substance abuse] = Psychological + Physiological dependence

• Psychological = compulsive drug seeking, craving• Physiological = symptoms and signs opposite to

drug.• Tolerance.

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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.

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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.

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YOUR BRAIN ON DRUGS

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

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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.

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THE REWARD PATHWAY

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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.

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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.

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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.

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Alcohol

Decreases the actions of the excitatory NMDA receptor complex, i.e., it diminishes excitation.•Enhances GABA inhibition.•Reduces glutamate excitation. •Enhances euphoric effects by releasing Opiates and endocannabinoids, thereby mediating its "high."

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DRUG ABUSE AND ADDICTION

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

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THE MESOLIMBIC DOPAMINERGIC REWARD PATHWAY

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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.

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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.

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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.

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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.

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THANK YOUHAVE A NICE DAY