SubPDF substance Use Disorders pharmacology
CalebKoomson
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131 slides
Jun 12, 2024
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About This Presentation
pharmacology
Slide Content
Substance
Use
Disorders
PHARM KWAME OPOKU -AGYEMAN
CLINICAL PHARMACOLOGIST/HEAD OF PHARMACY,
SDA HOSPITAL, KWADASO
BPHARM.MPHIL
6/6/2021 0
SSN372
Use
Disorders
PHARM KWAME OPOKU -AGYEMAN
CLINICAL PHARMACOLOGIST/HEAD OF PHARMACY,
SDA HOSPITAL, KWADASO
BPHARM.MPHIL
6/6/2021 0
SSN372
OBJECTIVES
I.Appreciate the scope and meaning of Substance
use Disorders, drug abuse, dependence, tolerance,
addiction, withdrawal syndrome and sensitization
II.Identify factors or variables that underly the
development of substance use disorders
III.list and understand the criteria for diagnosis of
Substance Dependence or addiction
IV.Understand the pharmacology of the mesolimbic
dopaminergic system or Brain Reward system
V.List the common drugs of Abuse and group them
based on their activity in the Brain Reward system
VI.General approach to the Addicted client or patient
6/6/2021 1
I.Appreciate the scope and meaning of Substance
use Disorders, drug abuse, dependence, tolerance,
addiction, withdrawal syndrome and sensitization
II.Identify factors or variables that underly the
development of substance use disorders
III.list and understand the criteria for diagnosis of
Substance Dependence or addiction
IV.Understand the pharmacology of the mesolimbic
dopaminergic system or Brain Reward system
V.List the common drugs of Abuse and group them
based on their activity in the Brain Reward system
VI.General approach to the Addicted client or patient
6/6/2021 1
Substance use disorder
•Substance use disorder (SUD) is the persistent use of
substances illegal or illicit despite substantial harm and
adverse consequences.
Or a problematicpattern of use” leading to “significant
impairment or distress.”
•Drug abuse refers to Inappropriateand usually excessive,
self-administration of a drug for non-medical purposes
•These comprise of illegal or illicit substances(heroin,
cocaine) as well as legally obtainable substances such as
tramadol or alcohol
•Most drugs of abuse exert an abuse potential based on
their pharmacological properties in the CNS
•Drug seeking behavior/reinforcing properties
6/6/2021 3
•Substance use disorder (SUD) is the persistent use of
substances illegal or illicit despite substantial harm and
adverse consequences.
Or a problematicpattern of use” leading to “significant
impairment or distress.”
•Drug abuse refers to Inappropriateand usually excessive,
self-administration of a drug for non-medical purposes
•These comprise of illegal or illicit substances(heroin,
cocaine) as well as legally obtainable substances such as
tramadol or alcohol
•Most drugs of abuse exert an abuse potential based on
their pharmacological properties in the CNS
•Drug seeking behavior/reinforcing properties
6/6/2021 3
Co-administration/Co-abuse
•Many of these drugs are used in combination with
other drugs from one or more categories
▪Alcohol Heroin
▪Nicotine Alcohol
▪cocaine heroin
▪Cocaine BDZs
▪Heroin BARBs
•Be aware of the possibility of combination of drugs
when treating withdrawal or overdose, each drug will
require a specific treatment
6/6/2021 4
•Many of these drugs are used in combination with
other drugs from one or more categories
▪Alcohol Heroin
▪Nicotine Alcohol
▪cocaine heroin
▪Cocaine BDZs
▪Heroin BARBs
•Be aware of the possibility of combination of drugs
when treating withdrawal or overdose, each drug will
require a specific treatment
6/6/2021 4
Tolerance
•Drugtoleranceisapharmacological
conceptdescribingsubjects'reduced
reactiontoadrugfollowingits
repeateduse.
•Amarkedincreaseinamountof
substancetoproducesameeffect
•Amarkeddiminishedeffectaftersame
doseorquantity
•Increasingitsdosagemayre-amplify
thedrug'seffects;however,thismay
acceleratetolerance,further
reducingthedrug'seffects.
•Thetoxicityandlethalityprofile
howeverdoesnotshifttothesame
magnitudeordoesn’tshiftatall.This
reducesthetherapeuticindex
6/6/2021 5
A
B
•Drugtoleranceisapharmacological
conceptdescribingsubjects'reduced
reactiontoadrugfollowingits
repeateduse.
•Amarkedincreaseinamountof
substancetoproducesameeffect
•Amarkeddiminishedeffectaftersame
doseorquantity
•Increasingitsdosagemayre-amplify
thedrug'seffects;however,thismay
acceleratetolerance,further
reducingthedrug'seffects.
•Thetoxicityandlethalityprofile
howeverdoesnotshifttothesame
magnitudeordoesn’tshiftatall.This
reducesthetherapeuticindex
6/6/2021 5
A
B
Tolerance…
•INNATE TOLERANCE-pre-existing inter individual
variations in sensitivity to a drug (often present
before drugs are given)
•ACQUIRED TOLERANCE-these are not present at
birth but is developed upon exposure to the drug.
1.Pharmacokinetic-
•Capacity to metabolize or excrete substance increases due to
enzyme inhibition or induction
2. Pharmacodynamic adaptation-
•Short term adaption result in increased or decreased in
neurotransmitter release, synapse clearance, number of
receptors, altered conduction of ions or modified signal
transduction
•long term adaptation or synaptic plasticity-alteration in gene
expression which influence receptor synthesis
6/6/2021 6
•INNATE TOLERANCE-pre-existing inter individual
variations in sensitivity to a drug (often present
before drugs are given)
•ACQUIRED TOLERANCE-these are not present at
birth but is developed upon exposure to the drug.
1.Pharmacokinetic-
•Capacity to metabolize or excrete substance increases due to
enzyme inhibition or induction
2. Pharmacodynamic adaptation-
•Short term adaption result in increased or decreased in
neurotransmitter release, synapse clearance, number of
receptors, altered conduction of ions or modified signal
transduction
•long term adaptation or synaptic plasticity-alteration in gene
expression which influence receptor synthesis
6/6/2021 6
Tolerance…
•Cross-tolerance
••When an individual has become tolerant to a drug
and requires higher than normal doses of a second
drug to have its effects(Chronic alcohol–anesthetic
agents, heroin-pethidine , Amphetamine-cocaine,
diazepam-alcohol , diazepam-barbiturates)
•Enzyme induction
•As a general rule cross tolerance occurs among
drugs in the same class or similar activity
6/6/2021 7
•Cross-tolerance
••When an individual has become tolerant to a drug
and requires higher than normal doses of a second
drug to have its effects(Chronic alcohol–anesthetic
agents, heroin-pethidine , Amphetamine-cocaine,
diazepam-alcohol , diazepam-barbiturates)
•Enzyme induction
•As a general rule cross tolerance occurs among
drugs in the same class or similar activity
6/6/2021 7
Sensitization
•Sensitization is a non-
associativeprocess in which
repeated administration of a
stimulus results in the
progressive amplification of a
response.
•A marked decrease in amount of
substance to produce same
effect
•A marked increased or
exaggerated effect after same
dose or quantity
•Sensitization often is
characterized by an
enhancement of response to
the same substance or within
its class.
6/6/2021 8
•Sensitization is a non-
associativeprocess in which
repeated administration of a
stimulus results in the
progressive amplification of a
response.
•A marked decrease in amount of
substance to produce same
effect
•A marked increased or
exaggerated effect after same
dose or quantity
•Sensitization often is
characterized by an
enhancement of response to
the same substance or within
its class.
6/6/2021 8
Dependence
•Drug dependence typically occurs when you need one or more drugs
to function
•It is possible to be dependent on a drug without being addicted.
•Homeostatic set points are usually alteredto compensate for the
presence of the drug or substance resulting in either permanent or
temporary adaptive states
•Physiological dependence (Physical dependence)-
•Psychological dependence (Addiction)
•Combination of both
•a compulsion to take the drug on a continuous or periodic basis
in order to experience its psychic effects or sometimes to
avoid the discomfort of its absence’
6/6/2021 9
•Drug dependence typically occurs when you need one or more drugs
to function
•It is possible to be dependent on a drug without being addicted.
•Homeostatic set points are usually alteredto compensate for the
presence of the drug or substance resulting in either permanent or
temporary adaptive states
•Physiological dependence (Physical dependence)-
•Psychological dependence (Addiction)
•Combination of both
•a compulsion to take the drug on a continuous or periodic basis
in order to experience its psychic effects or sometimes to
avoid the discomfort of its absence’
6/6/2021 9
Physiological (physical) Dependence
•Physical dependence is a state that develops as a result of the
adaptation (tolerance) produced by a resetting of homeostatic
mechanisms in response to repeated drug use.
•A person in this adapted state requires continued administration
of the drug to maintain near normal function of body organs or
systems.
•If administration of the drug is stopped abruptly, there is another
imbalance, and the affected systems must readjust to a new
equilibrium without the drug.
•Removal of the drug from body or from its active site by
administration of an antagonist produces withdrawal (abstinence,
absence) syndrome.
•If the substance is withdrawn the altered set points produce
effects opposite to those manifested in the presence of the drug
6/6/2021 10
•Physical dependence is a state that develops as a result of the
adaptation (tolerance) produced by a resetting of homeostatic
mechanisms in response to repeated drug use.
•A person in this adapted state requires continued administration
of the drug to maintain near normal function of body organs or
systems.
•If administration of the drug is stopped abruptly, there is another
imbalance, and the affected systems must readjust to a new
equilibrium without the drug.
•Removal of the drug from body or from its active site by
administration of an antagonist produces withdrawal (abstinence,
absence) syndrome.
•If the substance is withdrawn the altered set points produce
effects opposite to those manifested in the presence of the drug
6/6/2021 10
Psychological dependence(Addiction)
•Is a more complex phenomenon that can occur
even with drugs that do not normally induce
tolerance or physiological dependence.
•It usually affects the reward system of the brain.
•The pleasurable sensations cause the user to
continually seek for the substance or activity.
•Psychological and physical dependence usually co-
exist in the addicted individual
6/6/2021 11
•Is a more complex phenomenon that can occur
even with drugs that do not normally induce
tolerance or physiological dependence.
•It usually affects the reward system of the brain.
•The pleasurable sensations cause the user to
continually seek for the substance or activity.
•Psychological and physical dependence usually co-
exist in the addicted individual
6/6/2021 11
Non-substance addiction
•Non-substance addiction includes things such as
gambling, sex, food, the internet, mobile devices,
and shopping.
•These are sometimes called behavioral Addictions.
•A person with a non-substance addiction is unable
to stop doing the troublesome activity or behavior
•Behavior provides a “rush”or a thrill.
6/6/2021 12
•Non-substance addiction includes things such as
gambling, sex, food, the internet, mobile devices,
and shopping.
•These are sometimes called behavioral Addictions.
•A person with a non-substance addiction is unable
to stop doing the troublesome activity or behavior
•Behavior provides a “rush”or a thrill.
6/6/2021 12
Dopamine Receptors
•Dopamine is the primary neurotransmitter involved
in the reward pathway in the brain.
•Thus, drugs that increase dopamine signaling may
produce euphoric effects
•Receptors implicated in addictions are D
1and
D5
•Coupled to Gs which activates AC activity leading
to increased levels of 2
nd
messenger (cAMP)
•D
2, D
3and D
4 are coupled to Gi which deactivates
AC leading to decreased levels of 2
nd
Messenger
(cAMP)
6/6/2021 13
•Dopamine is the primary neurotransmitter involved
in the reward pathway in the brain.
•Thus, drugs that increase dopamine signaling may
produce euphoric effects
•Receptors implicated in addictions are D
1and
D5
•Coupled to Gs which activates AC activity leading
to increased levels of 2
nd
messenger (cAMP)
•D
2, D
3and D
4 are coupled to Gi which deactivates
AC leading to decreased levels of 2
nd
Messenger
(cAMP)
6/6/2021 13
Brain Reward pathway
•Also referred to as the Mesolimbic dopaminergic
pathway.
•Ventral Tegmental Area, Nucleus Accumbensand the
connecting dopaminergic neurons
•All drugs or activities with abuse potential target the
MDP.
•Drugs of abuse induce
•increased endogenous dopamine release at synaptic clefts
•Prevent reuptake into nerve ending
•Deactivate elimination of dopamine from target site by
enzyme inhibition
•inhibition of GABAergic (inhibitory) pathways
•Directly stimulate dopamine receptors
6/6/2021 14
•Also referred to as the Mesolimbic dopaminergic
pathway.
•Ventral Tegmental Area, Nucleus Accumbensand the
connecting dopaminergic neurons
•All drugs or activities with abuse potential target the
MDP.
•Drugs of abuse induce
•increased endogenous dopamine release at synaptic clefts
•Prevent reuptake into nerve ending
•Deactivate elimination of dopamine from target site by
enzyme inhibition
•inhibition of GABAergic (inhibitory) pathways
•Directly stimulate dopamine receptors
6/6/2021 14
Brain Reward pathway
6/6/2021 15
6/6/2021 15
6/6/2021 16
Natural Reward Mechanisms
•In an intact or uncompromised brain the mesolimbic
pathway serves as a reinforcer of good behavior.
•Natural rewards such as money, appreciation, praise,
achievement, success, expectation and surprises activate
these areas. Thus the brain is trained to work in order to
receive these rewards
•Punishment, criticism, disappointment and other negative
social activity which is frowned upon decrease levels of
dopamine in the VTA and enhances GABA activation leading
to dysphoria, sadness, crying etcthis links such activities to
the feeling thus disassociation
6/6/2021 17
•In an intact or uncompromised brain the mesolimbic
pathway serves as a reinforcer of good behavior.
•Natural rewards such as money, appreciation, praise,
achievement, success, expectation and surprises activate
these areas. Thus the brain is trained to work in order to
receive these rewards
•Punishment, criticism, disappointment and other negative
social activity which is frowned upon decrease levels of
dopamine in the VTA and enhances GABA activation leading
to dysphoria, sadness, crying etcthis links such activities to
the feeling thus disassociation
6/6/2021 17
Major connections of the
mesolimbic dopamine
system in the brain.
The compromised MDP
hijacks
•Arousal function
•Cognitive (thinking
ability)
•Emotional center
•Judgment function
•Decision making
•Executive Function
•Distortion of memory
6/6/2021 18
mesolimbic dopamine
system in the brain.
The compromised MDP
hijacks
•Arousal function
•Cognitive (thinking
ability)
•Emotional center
•Judgment function
•Decision making
•Executive Function
•Distortion of memory
6/6/2021 18
Neuronal adaptation
•A. In chronic substance exposure, pathways enhancing drug
effects are reducedto regain equilibrium and avoid
overstimulation.
•A reduction in neurofilament size which decreases the
size of the VTA
•Dopamine synthetic pathway rate limiting factors are
reduced
•D1 and D5 receptors responsible for observed effects of
euphoria are downregulated, internalized and their
transcription is reduced
•Decoupling of 2
nd
messenger relays to decrease effect size
6/6/2021 19
•A. In chronic substance exposure, pathways enhancing drug
effects are reducedto regain equilibrium and avoid
overstimulation.
•A reduction in neurofilament size which decreases the
size of the VTA
•Dopamine synthetic pathway rate limiting factors are
reduced
•D1 and D5 receptors responsible for observed effects of
euphoria are downregulated, internalized and their
transcription is reduced
•Decoupling of 2
nd
messenger relays to decrease effect size
6/6/2021 19
Neuronal adaptation
•B. To re-establish homeostasis in the presence of
the drug pro-inhibitory pathways of the brain are
enhanced
•Upregulation of inhibitory receptors
•receptor subtypes especially less responsive to
the abuse agents or drugs are increased,
•The Nucleus Accumbensbranches out and
enlarges
•Production of inhibitory neurotransmitters
increase
•The process of achieving the new equilibrium is
called Allostasis
6/6/2021 20
•B. To re-establish homeostasis in the presence of
the drug pro-inhibitory pathways of the brain are
enhanced
•Upregulation of inhibitory receptors
•receptor subtypes especially less responsive to
the abuse agents or drugs are increased,
•The Nucleus Accumbensbranches out and
enlarges
•Production of inhibitory neurotransmitters
increase
•The process of achieving the new equilibrium is
called Allostasis
6/6/2021 20
Allostasis...
•Allostasis is defined as the process of maintaining
homeostasis through the adaptive change of the
organism’s internal environment to meet perceived
and anticipated demands.
•Allostatic equilibrium after a period becomes
permanent and may remain unchanged even if the
addict later weans himself of the drug of abuse.
•In the absence of the drug of abuse the effects opposite
to the ones produced by the drug escalates resulting in
depression, lack of reward, demotivation, seizures and
sometimes suicidal tendencies.
•This forms one of the major reasons of relapse into
drug use years after a successful rehabilitation.
6/6/2021 21
•Allostasis is defined as the process of maintaining
homeostasis through the adaptive change of the
organism’s internal environment to meet perceived
and anticipated demands.
•Allostatic equilibrium after a period becomes
permanent and may remain unchanged even if the
addict later weans himself of the drug of abuse.
•In the absence of the drug of abuse the effects opposite
to the ones produced by the drug escalates resulting in
depression, lack of reward, demotivation, seizures and
sometimes suicidal tendencies.
•This forms one of the major reasons of relapse into
drug use years after a successful rehabilitation.
6/6/2021 21
Anatomical adaptations in Addiction
6/6/2021 22
6/6/2021 22
Variables of Drug addiction
•Drug /Agent factors -Availability, Cost, potency, Mode
of administration, pharmacokinetics
•Host factors –Heredity, Metabolism of the drug,
Psychiatric symptoms, Prior experiences/expectations,
Propensity for risk-taking behavior
•Environmental factors -Social setting, Community
attitudes, Peer influence, role models, Availability of
other reinforcers (sources of pleasure or recreation)
Employment or educational opportunities, Conditioned
stimuli
6/6/2021 23
•Drug /Agent factors -Availability, Cost, potency, Mode
of administration, pharmacokinetics
•Host factors –Heredity, Metabolism of the drug,
Psychiatric symptoms, Prior experiences/expectations,
Propensity for risk-taking behavior
•Environmental factors -Social setting, Community
attitudes, Peer influence, role models, Availability of
other reinforcers (sources of pleasure or recreation)
Employment or educational opportunities, Conditioned
stimuli
6/6/2021 23
DSM V criteria for Drug addiction
(SUD)
1.The substance is often taken in larger amounts or over a
longer period than was intended.
2.There is a persistent desire or unsuccessful efforts to
cutdown or control substance use.
3.A great deal of time is spent in activities necessary to
obtain the substance (e.g., visiting multiple doctors or
driving long distances), to use the substance (e.g., chain
smoking),or to recover from its effects.
4.Craving, or a strong desire or urge to use the substance.
5.Recurrent substance use resulting in a failure to fulfill
major role obligations at work, school, or home.
6.Continued substance use despite having persistent or
recurrent social or interpersonal problems caused or
exacerbated by the effects o the substance.
6/6/2021 24
(SUD)
1.The substance is often taken in larger amounts or over a
longer period than was intended.
2.There is a persistent desire or unsuccessful efforts to
cutdown or control substance use.
3.A great deal of time is spent in activities necessary to
obtain the substance (e.g., visiting multiple doctors or
driving long distances), to use the substance (e.g., chain
smoking),or to recover from its effects.
4.Craving, or a strong desire or urge to use the substance.
5.Recurrent substance use resulting in a failure to fulfill
major role obligations at work, school, or home.
6.Continued substance use despite having persistent or
recurrent social or interpersonal problems caused or
exacerbated by the effects o the substance.
6/6/2021 24
DSM V criteria for Drug addiction
(SUD)…
7.Recurrent substance use in situations in which it is physically
hazardous.
8.Substance use is continued despite knowledge of having a
persistent or recurrent physical or psychological problem that is
likely to have been caused or exacerbated by the substance (e.g.,
current cocaine use despite recognition of cocaine induced
depression, or continued drinking despite recognition that an
ulcer was made worse by alcohol consumption).
9.Tolerance, as defined by either of the following:
a.A need or markedly increased amounts of the substance to
achieve intoxication or desired effect.
b.A markedly diminished effect with continued use of the same
amount of substance.
6/6/2021 25
(SUD)…
7.Recurrent substance use in situations in which it is physically
hazardous.
8.Substance use is continued despite knowledge of having a
persistent or recurrent physical or psychological problem that is
likely to have been caused or exacerbated by the substance (e.g.,
current cocaine use despite recognition of cocaine induced
depression, or continued drinking despite recognition that an
ulcer was made worse by alcohol consumption).
9.Tolerance, as defined by either of the following:
a.A need or markedly increased amounts of the substance to
achieve intoxication or desired effect.
b.A markedly diminished effect with continued use of the same
amount of substance.
6/6/2021 25
DSM V criteria for Drugaddiction
(SUD)…
10 . Withdrawal, as manifested by either of the following:
a.The characteristic withdrawal syndrome of the substance
(as defined by the APA criteria or withdrawal or a specific
substance).
b.The same (or closely related) substance is taken to relieve
or avoid withdrawal symptoms.
6/6/2021 26
(SUD)…
10 . Withdrawal, as manifested by either of the following:
a.The characteristic withdrawal syndrome of the substance
(as defined by the APA criteria or withdrawal or a specific
substance).
b.The same (or closely related) substance is taken to relieve
or avoid withdrawal symptoms.
6/6/2021 26
Classification
•Mild
•Two to three symptoms per an individual based on DSM
•MODERATE
•Four to five symptoms 4–5 symptoms
•SEVERE
•Six or more symptoms per an individual
6/6/2021 27
•Mild
•Two to three symptoms per an individual based on DSM
•MODERATE
•Four to five symptoms 4–5 symptoms
•SEVERE
•Six or more symptoms per an individual
6/6/2021 27
Commonly Abused Drugs
✓Opioids/narcotic analgesics-
•Heroin, morphine, codeine, tramadol
✓CNS Depressants
•Alcohol , Sedative/Hypnotics, Anxiolytics
✓CNS Stimulants
•Cocaine, Amphetamines, Methylxanthines, Nicotine
✓Drugs causing hallucinations, delusions or
dissociative disorders
•Psychedelics and hallucinogens, Marijuana (Cannabis),
Dissociative anesthetics (PCP), Anticholinergics
6/6/2021 28
✓Opioids/narcotic analgesics-
•Heroin, morphine, codeine, tramadol
✓CNS Depressants
•Alcohol , Sedative/Hypnotics, Anxiolytics
✓CNS Stimulants
•Cocaine, Amphetamines, Methylxanthines, Nicotine
✓Drugs causing hallucinations, delusions or
dissociative disorders
•Psychedelics and hallucinogens, Marijuana (Cannabis),
Dissociative anesthetics (PCP), Anticholinergics
6/6/2021 28
GENERAL
APPROACH TO
AN ADDICT
•DON’T BE QUICK TO JUDGE –EXCESSIVE
DYSPHORIA
•LISTEN TO THEIR CONCERNS
•REMOVE REMINDERS OF ADDICTION OR
SOCIAL CUES OR CHANGE THE
ENVIRONMENT
•ENGAGE IN OTHER ACTIVITIES WITH A
CAPACITY TO REWARD
•GROUP TREATMENT ENHANCES POSITIVE
FEELING.
•ENORMOUS FAMILY SUPPORT FOR THE
ADDICT
•ENCOURAGE EVEN IF THERE IS RELAPSE
•VERY POSITVE MOTIVATION
ADDICTS JUST WANT TO LIVE A NORMAL LIFE
6/6/2021 29
APPROACH TO
AN ADDICT
•DON’T BE QUICK TO JUDGE –EXCESSIVE
DYSPHORIA
•LISTEN TO THEIR CONCERNS
•REMOVE REMINDERS OF ADDICTION OR
SOCIAL CUES OR CHANGE THE
ENVIRONMENT
•ENGAGE IN OTHER ACTIVITIES WITH A
CAPACITY TO REWARD
•GROUP TREATMENT ENHANCES POSITIVE
FEELING.
•ENORMOUS FAMILY SUPPORT FOR THE
ADDICT
•ENCOURAGE EVEN IF THERE IS RELAPSE
•VERY POSITVE MOTIVATION
ADDICTS JUST WANT TO LIVE A NORMAL LIFE
6/6/2021 29
Case study
•The emergency department contacts a medical
toxicologist with a question regarding a patient seen
frequently for pain complaints.
•His outpatient providers have been managing his
opioid therapies for chronic pain, but the patient often
runs out of pills early, misses scheduled pills counts, or
has non-prescribed substances identified on urine drug
testing.
•The patient denies that he has an addiction problem
and states his increased use is due to uncontrolled
pain.
•The provider asks whether these behaviors are due to
addiction or pain, and if this patient should be referred
to addiction medicine.
How is Opioid use for Pain Versus Addiction
Differentiated?
6/6/2021 30
•The emergency department contacts a medical
toxicologist with a question regarding a patient seen
frequently for pain complaints.
•His outpatient providers have been managing his
opioid therapies for chronic pain, but the patient often
runs out of pills early, misses scheduled pills counts, or
has non-prescribed substances identified on urine drug
testing.
•The patient denies that he has an addiction problem
and states his increased use is due to uncontrolled
pain.
•The provider asks whether these behaviors are due to
addiction or pain, and if this patient should be referred
to addiction medicine.
How is Opioid use for Pain Versus Addiction
Differentiated?
6/6/2021 30
Enhancing Motivation to Quit:
The “5 R’s”
•Relevance
•Encourage patients to think about the reasons why
quitting is important.
•Counseling should be framed such that it relates to the
patient’s risk for disease or exacerbation of disease,
family or social situations
•e.g. having children with asthma, maternal deformity ,
health concerns, age, or other patient factors, such as
prior experience with quitting.
6/6/2021 31
The “5 R’s”
•Relevance
•Encourage patients to think about the reasons why
quitting is important.
•Counseling should be framed such that it relates to the
patient’s risk for disease or exacerbation of disease,
family or social situations
•e.g. having children with asthma, maternal deformity ,
health concerns, age, or other patient factors, such as
prior experience with quitting.
6/6/2021 31
Enhancing Motivation to Quit:
The “5 R’s”
•Risks—
•Ask patients to identify potential negative health
consequences of ABUSE, such as
•acute risks (divorce, asthma exacerbations, harm to
pregnancy, infertility, loss of livelihood)
•long-term risks (cancer, cardiac, and pulmonary
disease),
•environmental risks (promoting drug abuse among
children by being a negative role model; effects of
secondhand smoke on others, including children and
pets).
6/6/2021 32
The “5 R’s”
•Risks—
•Ask patients to identify potential negative health
consequences of ABUSE, such as
•acute risks (divorce, asthma exacerbations, harm to
pregnancy, infertility, loss of livelihood)
•long-term risks (cancer, cardiac, and pulmonary
disease),
•environmental risks (promoting drug abuse among
children by being a negative role model; effects of
secondhand smoke on others, including children and
pets).
6/6/2021 32
Enhancing Motivation to Quit:
The “5 R’s”
•Rewards—
•Ask patients to identify potential benefits that they
anticipate from quitting, such as
•Personal health -improved health, enhanced physical
performance, enhanced taste and smell,
•Job and financial security -reduced expenditures for
tobacco, less time wasted or work missed,
•Family-reduced health risks to others (fetus, children,
housemates),
6/6/2021 33
The “5 R’s”
•Rewards—
•Ask patients to identify potential benefits that they
anticipate from quitting, such as
•Personal health -improved health, enhanced physical
performance, enhanced taste and smell,
•Job and financial security -reduced expenditures for
tobacco, less time wasted or work missed,
•Family-reduced health risks to others (fetus, children,
housemates),
6/6/2021 33
Enhancing Motivation to Quit:
The “5 R’s”
•Roadblocks—
•Help patients identify barriers to quitting and assist in
developing coping strategies for addressing each barrier.
•Common barriers include nicotine withdrawal symptoms
, fear of failure,
•a need forsocialsupport while quitting, depression,
weight gain, and a sense of deprivation or loss.
6/6/2021 34
The “5 R’s”
•Roadblocks—
•Help patients identify barriers to quitting and assist in
developing coping strategies for addressing each barrier.
•Common barriers include nicotine withdrawal symptoms
, fear of failure,
•a need forsocialsupport while quitting, depression,
weight gain, and a sense of deprivation or loss.
6/6/2021 34
Enhancing Motivation to Quit:
The “5 R’s”
•Repetition—
•Continue to work with patients who are successful in
their quit attempt.
•Discuss circumstances in which abuse occurred to
identify the trigger(s) for relapse; this is part of the
learning process and will be useful information for the
next quit attempt.
•Repeat interventions when possible.
6/6/2021 35
The “5 R’s”
•Repetition—
•Continue to work with patients who are successful in
their quit attempt.
•Discuss circumstances in which abuse occurred to
identify the trigger(s) for relapse; this is part of the
learning process and will be useful information for the
next quit attempt.
•Repeat interventions when possible.
6/6/2021 35
Components of
counselling
•ASK :
•ADVISE:
•ASSES
•ASSIST
•ARRANGE
6/6/2021 36
counselling
•ASK :
•ADVISE:
•ASSES
•ASSIST
•ARRANGE
6/6/2021 36
SUMMARY
•Appreciate the scope and meaning of Substance use
Disorders, drug abuse, dependence, tolerance,
addiction, withdrawal syndrome and sensitization
•Identify factors or variables that underly the
development of substance use disorders
•list and understand the criteria for diagnosis of
Substance Dependence or addiction
•Understand the pharmacology of the mesolimbic
dopaminergic system or Brain Reward system
•List the common drugs of Abuse and group them based
on their activity in the Brain Reward system
•General approach to the Addicted client or patient
6/6/2021 37
•Appreciate the scope and meaning of Substance use
Disorders, drug abuse, dependence, tolerance,
addiction, withdrawal syndrome and sensitization
•Identify factors or variables that underly the
development of substance use disorders
•list and understand the criteria for diagnosis of
Substance Dependence or addiction
•Understand the pharmacology of the mesolimbic
dopaminergic system or Brain Reward system
•List the common drugs of Abuse and group them based
on their activity in the Brain Reward system
•General approach to the Addicted client or patient
6/6/2021 37
6/6/2021 38
Specific Drugs of Abuse
CNS DEPRESSANTS
6/6/2021 39
CNS DEPRESSANTS
6/6/2021 39
OBJECTIVES
•List the CNS Depressants of clinical importance
•Appreciate the subcategories of CNS depressants
•Understand the epidemiology, pharmacokinetics
and pharmacodynamics of commonly abused CNS
depressants
•Understand the toxicity profile, medical and
pharmacotherapeutic options available for acute
poisoning, withdrawal syndrome and maintenance
of remission for some CNS depressants
6/6/2021 40
•List the CNS Depressants of clinical importance
•Appreciate the subcategories of CNS depressants
•Understand the epidemiology, pharmacokinetics
and pharmacodynamics of commonly abused CNS
depressants
•Understand the toxicity profile, medical and
pharmacotherapeutic options available for acute
poisoning, withdrawal syndrome and maintenance
of remission for some CNS depressants
6/6/2021 40
CNS DEPRESSANTS
•Central Nervous System Depressants essentially “slow
down” brain activity
•In higher doses they tend to be anaesthetic or induce
unconsciousness
•They are clinically useful in
•Insomnia, anxiety disorder, panic attacks, stress, pain,
seizures etc.
•Clinically useful as pharmacotherapy of CNS stimulants
toxicity
•Almost all CNS depressants have an addictive or Abuse
potential
•CNS Depressants tend to be sympatholytic
6/6/2021 41
•Central Nervous System Depressants essentially “slow
down” brain activity
•In higher doses they tend to be anaesthetic or induce
unconsciousness
•They are clinically useful in
•Insomnia, anxiety disorder, panic attacks, stress, pain,
seizures etc.
•Clinically useful as pharmacotherapy of CNS stimulants
toxicity
•Almost all CNS depressants have an addictive or Abuse
potential
•CNS Depressants tend to be sympatholytic
6/6/2021 41
SHORT TERM EFFECTS
•Lowered Blood
pressure
•Dilated Pupils
•Confusion or
disorientation
•Bradycardia
•apnoea
•Sleepiness and fatigue
•Dizziness
•Difficulty concentrating
•Memory loss
•Slowed reaction
•Relaxation and
euphoria
•Slurred speech
•Loss of coordination
6/6/2021 42
•Lowered Blood
pressure
•Dilated Pupils
•Confusion or
disorientation
•Bradycardia
•apnoea
•Sleepiness and fatigue
•Dizziness
•Difficulty concentrating
•Memory loss
•Slowed reaction
•Relaxation and
euphoria
•Slurred speech
•Loss of coordination
6/6/2021 42
LONG TERM EFFECTS
•Weight gain
•Hypersomnia
•Sexual dysfunction
•Breathing and sleep
disorders
•Suicidal tendencies
•Physical and
psychological
dependence
TOXICITY
•Hypothermia
•Dilated unresponsive
pupils
•Respiratory failure
•Lethargy
•Heart failure
•Loss of homeostasis
•Death
6/6/2021 43
•Weight gain
•Hypersomnia
•Sexual dysfunction
•Breathing and sleep
disorders
•Suicidal tendencies
•Physical and
psychological
dependence
TOXICITY
•Hypothermia
•Dilated unresponsive
pupils
•Respiratory failure
•Lethargy
•Heart failure
•Loss of homeostasis
•Death
6/6/2021 43
Withdrawal include
•Insomnia
•Restlessness
•Nausea
•Vomiting
•tremors
•Weakness
•Excessive sweating
•Irritability
•hallucinations
•Panic attacks
•Body tremors
•Seizures
•Manic disorders
•Muscular stiffness
•High BP with rapid
pulse
•Hypersensitivity to light
and sounds
•Aches and pain
6/6/2021 44
•Insomnia
•Restlessness
•Nausea
•Vomiting
•tremors
•Weakness
•Excessive sweating
•Irritability
•hallucinations
•Panic attacks
•Body tremors
•Seizures
•Manic disorders
•Muscular stiffness
•High BP with rapid
pulse
•Hypersensitivity to light
and sounds
•Aches and pain
6/6/2021 44
COMMONLY ABUSED CNS
DEPRESSANTS
•ALCOHOL
•OPIOIDS
•BENZODIAZEPINES
•BARBITURATES
•GAMMA-HYDROXYBUTYRIC ACID (GHB)
6/6/2021 45
DEPRESSANTS
•ALCOHOL
•OPIOIDS
•BENZODIAZEPINES
•BARBITURATES
•GAMMA-HYDROXYBUTYRIC ACID (GHB)
6/6/2021 45
Alcohol
6/6/2021 46
6/6/2021 46
Epidemiology
•It is the most widely abused Drug or substance in the
world
•As many as half of all traffic accidents,
•two-thirds of homicides, and three-fourths of suicides
•it is a significant factor in crimes
•family problems, and in personal and industrial
accidents.
•The annual cost to the American economy has been
estimated to exceed $100 billion in lost productivity,
medical care, and property damage.
6/6/2021 47
•It is the most widely abused Drug or substance in the
world
•As many as half of all traffic accidents,
•two-thirds of homicides, and three-fourths of suicides
•it is a significant factor in crimes
•family problems, and in personal and industrial
accidents.
•The annual cost to the American economy has been
estimated to exceed $100 billion in lost productivity,
medical care, and property damage.
6/6/2021 47
Medical uses
•To relieve long-lasting pain
•Dehydrated alcohol may be injected in close proximity to
nerves or sympathetic ganglia
•Epidural, subarachnoid, and lumbar paravertebral
injections of ethanol may destroy sympathetic ganglia
and thereby produce vasodilation and relieve pain
•Treatment of poisoning by methyl alcohol and
ethylene glycol
•Disinfectant or antiseptic
•Solvent in many extraction processes
6/6/2021 48
•To relieve long-lasting pain
•Dehydrated alcohol may be injected in close proximity to
nerves or sympathetic ganglia
•Epidural, subarachnoid, and lumbar paravertebral
injections of ethanol may destroy sympathetic ganglia
and thereby produce vasodilation and relieve pain
•Treatment of poisoning by methyl alcohol and
ethylene glycol
•Disinfectant or antiseptic
•Solvent in many extraction processes
6/6/2021 48
Distribution…
•It readily equilibrates in organs with high blood
perfusion such as the brain, lungs, liver and kidney
and conversely in low perfused organs such as
muscles.
•It readily crosses into the blood brain barrier and
the blood placental barrier by simple diffusion
6/6/2021 49
•It readily equilibrates in organs with high blood
perfusion such as the brain, lungs, liver and kidney
and conversely in low perfused organs such as
muscles.
•It readily crosses into the blood brain barrier and
the blood placental barrier by simple diffusion
6/6/2021 49
Metabolism
•Primarily metabolized in the liver -90-98%
•Alcohol dehydrogenase
•Mixed function microsomal oxidase(cytochrome P450 2
EI) or Microsomal Ethanol oxidising system (MEOS)
•The rest is excreted unchanged in urine and expired
air-2-10%
6/6/2021 50
•Primarily metabolized in the liver -90-98%
•Alcohol dehydrogenase
•Mixed function microsomal oxidase(cytochrome P450 2
EI) or Microsomal Ethanol oxidising system (MEOS)
•The rest is excreted unchanged in urine and expired
air-2-10%
6/6/2021 50
Primary Route
of Metabolism
1.ADH and ALDH
•90-98% of alcohol
is metabolized in
liver, mainly by
successive oxidation
by alcohol
dehydrogenase
(ADH) and aldehyde
dehydrogenase
6/6/2021 51
of Metabolism
1.ADH and ALDH
•90-98% of alcohol
is metabolized in
liver, mainly by
successive oxidation
by alcohol
dehydrogenase
(ADH) and aldehyde
dehydrogenase
6/6/2021 51
Alcohol use disorder
•Alcohol is the most commonly abused legal
recreational drug
•Alcohol use disorder is defined as four or more
criteria as defined by DSM5 manual
6/6/2021 52
•Alcohol is the most commonly abused legal
recreational drug
•Alcohol use disorder is defined as four or more
criteria as defined by DSM5 manual
6/6/2021 52
Hangover
•A hangover is a group of unpleasant signs and
symptoms that can develop after drinking too much
alcohol.
•Fatigue and weakness
•Excessive thirst and dry mouth
•Headaches and muscle aches
•Nausea, vomiting or stomach pain
•Poor or decreased sleep
•Increased sensitivity to light and sound
•Dizziness or a sense of the room spinning
•Shakiness
•Decreased ability to concentrate
•Mood disturbances, such as depression, anxiety and
irritability
•Rapid heartbeat
6/6/2021 53
•A hangover is a group of unpleasant signs and
symptoms that can develop after drinking too much
alcohol.
•Fatigue and weakness
•Excessive thirst and dry mouth
•Headaches and muscle aches
•Nausea, vomiting or stomach pain
•Poor or decreased sleep
•Increased sensitivity to light and sound
•Dizziness or a sense of the room spinning
•Shakiness
•Decreased ability to concentrate
•Mood disturbances, such as depression, anxiety and
irritability
•Rapid heartbeat
6/6/2021 53
Hangover causes
•Alcohol causes diuresis leading to dehydration,
dizziness, thirst and lightheadedness
•Alcohol triggers an inflammatory response from your
immune system due to the direct toxicity of
acetaldehyde and alcohol on neurons.
•Alcohol directly irritates the lining of your stomach and
stimulates acid secretion.
•Alcohol causes hypoglycemia by inhibiting liver
gluconeogenesis.
•Alcohol and acetaldehyde causes generalized
vasodilation of some blood vessels.
•Alcohol induces intense sedation but not deep sleep
6/6/2021 54
•Alcohol causes diuresis leading to dehydration,
dizziness, thirst and lightheadedness
•Alcohol triggers an inflammatory response from your
immune system due to the direct toxicity of
acetaldehyde and alcohol on neurons.
•Alcohol directly irritates the lining of your stomach and
stimulates acid secretion.
•Alcohol causes hypoglycemia by inhibiting liver
gluconeogenesis.
•Alcohol and acetaldehyde causes generalized
vasodilation of some blood vessels.
•Alcohol induces intense sedation but not deep sleep
6/6/2021 54
Management
•Fluid replacement especially k
+
rich fluids
•Ringers lactate in hospitalized patients
•Plenty of rest
•Antacids for upset stomach
•Aluminiumbased atacids>>magnesium based
•Pain medication of NSAIDS are recommended but
avoid Acetaminophen as it can exacerbate
hepatotoxicity.
6/6/2021 55
•Fluid replacement especially k
+
rich fluids
•Ringers lactate in hospitalized patients
•Plenty of rest
•Antacids for upset stomach
•Aluminiumbased atacids>>magnesium based
•Pain medication of NSAIDS are recommended but
avoid Acetaminophen as it can exacerbate
hepatotoxicity.
6/6/2021 55
Acute alcohol
Intoxication
•Confusion
•Vomiting
•Seizures
•Slow breathing (less than eight
breaths a minute)
•Apneustic breathing
•Blue-tinged skin or pale skin
•Hypothermia
•Difficulty remaining conscious
•Unconsciousness
0.18-
0.45
BAC
6/6/2021 56
Intoxication
•Confusion
•Vomiting
•Seizures
•Slow breathing (less than eight
breaths a minute)
•Apneustic breathing
•Blue-tinged skin or pale skin
•Hypothermia
•Difficulty remaining conscious
•Unconsciousness
0.18-
0.45
BAC
6/6/2021 56
Goals of treatment
•Prevention of respiratory depression or collapse
•Respiratory and cardiovascular support (Endotracheal intubation for
respiratory support )
•Prevention of aspiration of vomitus
•Position in recovery position and or suction of vomitus or intestinal
contents
•Electrolyte and fluid replacement
•Aggressive fluid replacement enhances organ reperfusion and
reduces end organ damage
•Electrolytes especially K+ rich fluids should be given
•Correction of Hypoglycemia if present
•Thiamine administration prevents several CNS effects EgWernicke-
Korsakoff syndrome
•Administration of 10% or 50% glucose corrects hypoglycemia and
ketoacidosis
6/6/2021 57
•Prevention of respiratory depression or collapse
•Respiratory and cardiovascular support (Endotracheal intubation for
respiratory support )
•Prevention of aspiration of vomitus
•Position in recovery position and or suction of vomitus or intestinal
contents
•Electrolyte and fluid replacement
•Aggressive fluid replacement enhances organ reperfusion and
reduces end organ damage
•Electrolytes especially K+ rich fluids should be given
•Correction of Hypoglycemia if present
•Thiamine administration prevents several CNS effects EgWernicke-
Korsakoff syndrome
•Administration of 10% or 50% glucose corrects hypoglycemia and
ketoacidosis
6/6/2021 57
Prevention of respiratory depression or collapse
•Emergency treatment strives to stabilize and
maintain an open airway and sufficient breathing,
while waiting for the alcohol to metabolize
•Provide oxygen therapy as needed via nasal
cannula or non-rebreather mask.
•Metabolic and respiratory acidosis may occur and
should be treated with sodium bicarbonate
infusions
6/6/2021 58
•Emergency treatment strives to stabilize and
maintain an open airway and sufficient breathing,
while waiting for the alcohol to metabolize
•Provide oxygen therapy as needed via nasal
cannula or non-rebreather mask.
•Metabolic and respiratory acidosis may occur and
should be treated with sodium bicarbonate
infusions
6/6/2021 58
Electrolyte and fluid replacement
•Hypotension and hypovolemia due to loss of
homeostatic control.
•Ringers lactate or Normal saline is appropriate
•If need for glucose administration thiamine
injection should be given first to avoid wernickes-
Korsakoff syndrome and encephalopathy
•Need for haemodialysis if BAC is above 0.5%
•NB.
•Dialysis often times induces acute withdrawal which
should recognised apart from toxicity
6/6/2021 59
•Hypotension and hypovolemia due to loss of
homeostatic control.
•Ringers lactate or Normal saline is appropriate
•If need for glucose administration thiamine
injection should be given first to avoid wernickes-
Korsakoff syndrome and encephalopathy
•Need for haemodialysis if BAC is above 0.5%
•NB.
•Dialysis often times induces acute withdrawal which
should recognised apart from toxicity
6/6/2021 59
Correction of Hypoglycemia if present
•largely related to decreased glycogen stores as well
as ethanol’s inhibition of gluconeogenesis
•Administer 50% glucose solution then monitor RBS.
•Maintenance with 5 or 10% glucose infusion if
hypoglycemia persist till patient recovers
6/6/2021 60
•largely related to decreased glycogen stores as well
as ethanol’s inhibition of gluconeogenesis
•Administer 50% glucose solution then monitor RBS.
•Maintenance with 5 or 10% glucose infusion if
hypoglycemia persist till patient recovers
6/6/2021 60
Withdrawal syndrome
•Mild to Moderate
•Sweats
•Tachycardia
•Tremors
•Insomnia
•Anxiety
•Psychomotor agitation
•Severe
•Generalized tonic clonicseizures
(10% of patients)
•Delirium tremens after 2-4 days (
5% )
•Hallucinations
Is a sign of physical
dependence
Maladaptation to the
presence of alcohol
in the system
6-8hrs after last drink
peaks between 24-36
hrs
6/6/2021 61
•Mild to Moderate
•Sweats
•Tachycardia
•Tremors
•Insomnia
•Anxiety
•Psychomotor agitation
•Severe
•Generalized tonic clonicseizures
(10% of patients)
•Delirium tremens after 2-4 days (
5% )
•Hallucinations
Is a sign of physical
dependence
Maladaptation to the
presence of alcohol
in the system
6-8hrs after last drink
peaks between 24-36
hrs
6/6/2021 61
Withdrawal
syndrome
Mediated primarily through
GABA and NMDA receptors
•Downregulation or
internalization of GABA –R
and synthesis of GABA
A()
receptors which is less
sensitive to alcohol
•Upregulation of NMDA-R
receptors and
•Neuronal excitation and
seizures
6/6/2021 62
syndrome
Mediated primarily through
GABA and NMDA receptors
•Downregulation or
internalization of GABA –R
and synthesis of GABA
A()
receptors which is less
sensitive to alcohol
•Upregulation of NMDA-R
receptors and
•Neuronal excitation and
seizures
6/6/2021 62
Treatment objectives
•Treatment objectives
•To relieve agitation and calm patient
•To prevent complications like seizures, development of
amnesia and encephalopathy
•To correct fluid and electrolyte imbalance
•To prevent or manage heart complications if present
•Fixed schedule regimen and Symptom-Triggered
Regimen
•Nurse in a quiet evenly lit room
6/6/2021 63
•Treatment objectives
•To relieve agitation and calm patient
•To prevent complications like seizures, development of
amnesia and encephalopathy
•To correct fluid and electrolyte imbalance
•To prevent or manage heart complications if present
•Fixed schedule regimen and Symptom-Triggered
Regimen
•Nurse in a quiet evenly lit room
6/6/2021 63
Treatment…
•Benzodiazepines are the drugs of choice
•Inhibit nerve-cell excitability binding to GABA -A receptors thus
pharmacologically substituting for alcohol in the brain
•Relieve withdrawal symptoms
•Prevent progression to delirium tremens
•Prevent the occurrence or reduce the duration of seizures
•Longer-acting benzodiazepines (Chlordiazepoxide,
clorazepate and diazepam)provide for easier weaning
because they gradually self-taper on metabolism and
excretion; this allows for less fluctuation in plasma drug
levels
6/6/2021 64
•Benzodiazepines are the drugs of choice
•Inhibit nerve-cell excitability binding to GABA -A receptors thus
pharmacologically substituting for alcohol in the brain
•Relieve withdrawal symptoms
•Prevent progression to delirium tremens
•Prevent the occurrence or reduce the duration of seizures
•Longer-acting benzodiazepines (Chlordiazepoxide,
clorazepate and diazepam)provide for easier weaning
because they gradually self-taper on metabolism and
excretion; this allows for less fluctuation in plasma drug
levels
6/6/2021 64
Treatment…
•Longer acting agentscause fewer rebound effects
and withdrawal seizures on discontinuation
•Shorter-acting agents (e.g., lorazepam or
oxazepam), which undergo hepatic metabolism to
inactive metabolites, require more frequent dosing
but may be more appropriate for alcoholics with
liver disease and the elderly.
•After the alcohol withdrawal syndrome has been
treated acutely, sedative-hypnotic medications
must be tapered slowly over several weeks.
6/6/2021 65
•Longer acting agentscause fewer rebound effects
and withdrawal seizures on discontinuation
•Shorter-acting agents (e.g., lorazepam or
oxazepam), which undergo hepatic metabolism to
inactive metabolites, require more frequent dosing
but may be more appropriate for alcoholics with
liver disease and the elderly.
•After the alcohol withdrawal syndrome has been
treated acutely, sedative-hypnotic medications
must be tapered slowly over several weeks.
6/6/2021 65
ADJUNCTIVE TREATMENTS
•Thiamine therapy (plus other multivitamins esp. folate)
to increase glucose utilization by brain
•Support with IV fluids may be necessary in those
patients with excessive losses through vomiting,
sweating, and hyperthermia
•Antipsychotics(e.g. haloperidol, quetiapine) can be
used for managing hallucinations and severe agitation,
but care must be used because these drugs can reduce
the seizure threshold
•Muscle relaxants e.g. baclofen GABA
Breceptor agonist,
skeletal muscle relaxant, and antispasmodic agent.
6/6/2021 66
•Thiamine therapy (plus other multivitamins esp. folate)
to increase glucose utilization by brain
•Support with IV fluids may be necessary in those
patients with excessive losses through vomiting,
sweating, and hyperthermia
•Antipsychotics(e.g. haloperidol, quetiapine) can be
used for managing hallucinations and severe agitation,
but care must be used because these drugs can reduce
the seizure threshold
•Muscle relaxants e.g. baclofen GABA
Breceptor agonist,
skeletal muscle relaxant, and antispasmodic agent.
6/6/2021 66
Alcoholism
•Goals of treatment
•To alleviate the acute
abstinence syndrome during
detoxification
•Benzodiazepines, clonidine,
propranolol
•To render alcohol consumption
unpleasant
•disulfiram
•To reduce craving
•Naltrexone, nalmefene, baclofen,
acamprosate
•To maintain remission
•Topiramate, acamprosate
Psychological and social
management
Group management
helps
6/6/2021 67
•Goals of treatment
•To alleviate the acute
abstinence syndrome during
detoxification
•Benzodiazepines, clonidine,
propranolol
•To render alcohol consumption
unpleasant
•disulfiram
•To reduce craving
•Naltrexone, nalmefene, baclofen,
acamprosate
•To maintain remission
•Topiramate, acamprosate
Psychological and social
management
Group management
helps
6/6/2021 67
Adjunctive therapy
•Benzodiazepines are the drugs of choice. the
barbiturates are obsolete now.
•clonidine(α
2-adrenoceptor agonist)act by
inhibiting the exaggerated transmitter release that
occurs during withdrawal
•Propranolol(β-adrenoceptor antagonist) blocks
some of the effects of excessive sympathetic
activity.
6/6/2021 68
•Benzodiazepines are the drugs of choice. the
barbiturates are obsolete now.
•clonidine(α
2-adrenoceptor agonist)act by
inhibiting the exaggerated transmitter release that
occurs during withdrawal
•Propranolol(β-adrenoceptor antagonist) blocks
some of the effects of excessive sympathetic
activity.
6/6/2021 68
Disulfiram
(Tetraethylthiuramdisulfide)
•Disulfiram irreversibly inactivates cytosolic and
mitochondrial forms of ALDH
•Increases the blood acetaldehyde concentration by 5–
10 times compared to the level measured when
ethanol is administered alone
•The first drug approved to treat alcohol abuse, is
relatively nontoxic when taken in the absence of
ethanol
•It induces severe “hangover”
•Sensitization may last for up to 14 days after last dose
of disulfiram
6/6/2021 69
(Tetraethylthiuramdisulfide)
•Disulfiram irreversibly inactivates cytosolic and
mitochondrial forms of ALDH
•Increases the blood acetaldehyde concentration by 5–
10 times compared to the level measured when
ethanol is administered alone
•The first drug approved to treat alcohol abuse, is
relatively nontoxic when taken in the absence of
ethanol
•It induces severe “hangover”
•Sensitization may last for up to 14 days after last dose
of disulfiram
6/6/2021 69
Disulfiram………..
•Several other drugs (e.g. metronidazole, cefotetan,
trimethoprim) inhibit ALDH and can cause a
disulfiram-like reaction if combined with ethanol
•It inhibits the metabolism of many other
therapeutic agents, including phenytoin, oral
anticoagulants, and isoniazid
•Disulfiram by itself usually is non toxic, but it may
cause acneformeruptions, urticaria, lassitude,
tremor, restlessness, headache, dizziness, a garlic-
like or metallic taste, and mild GI disturbances
•Peripheral neuropathies, psychosis, and ketosis also
have been reported
6/6/2021 70
•Several other drugs (e.g. metronidazole, cefotetan,
trimethoprim) inhibit ALDH and can cause a
disulfiram-like reaction if combined with ethanol
•It inhibits the metabolism of many other
therapeutic agents, including phenytoin, oral
anticoagulants, and isoniazid
•Disulfiram by itself usually is non toxic, but it may
cause acneformeruptions, urticaria, lassitude,
tremor, restlessness, headache, dizziness, a garlic-
like or metallic taste, and mild GI disturbances
•Peripheral neuropathies, psychosis, and ketosis also
have been reported
6/6/2021 70
Naltrexone
•μ-opioid receptor antagonist
•chemically related to naloxone but has higher oral
bioavailability and a longer duration of action when
administered orally
•Naltrexone reduces craving and decreases relapse
to heavy drinking.
•It is administered after detoxificationor “drying
out”
•It is typically administered after detoxification at a
dose of 50 mg/d for several months but monthly
depo injections are also available
6/6/2021 71
•μ-opioid receptor antagonist
•chemically related to naloxone but has higher oral
bioavailability and a longer duration of action when
administered orally
•Naltrexone reduces craving and decreases relapse
to heavy drinking.
•It is administered after detoxificationor “drying
out”
•It is typically administered after detoxification at a
dose of 50 mg/d for several months but monthly
depo injections are also available
6/6/2021 71
Naltrexone…
•The drug can cause dose-dependent hepatotoxicity
and should be used with caution in patients with
evidence of abnormalities in serum aminotransferase
activity.
•The combination of naltrexone plus disulfiram should
be avoided, since both drugs are potential
hepatotoxins
6/6/2021 72
•The drug can cause dose-dependent hepatotoxicity
and should be used with caution in patients with
evidence of abnormalities in serum aminotransferase
activity.
•The combination of naltrexone plus disulfiram should
be avoided, since both drugs are potential
hepatotoxins
6/6/2021 72
Acamprosate
(N-acetylhomotaurine)
•acamprosate has many molecular effects including
actions on GABA, glutamate, serotonergic,
noradrenergic, and dopaminergic receptors
•weak NMDA-receptor antagonist and a GABAA-R
activator
•widely distributed and is eliminated renally.
•It does not appear to participate in drug-drug
interactions.
•The most common adverse effects are gastrointestinal
(nausea, vomiting, diarrhea) and rash.
•It should not be used in patients with severe renal
impairment.
6/6/2021 73
(N-acetylhomotaurine)
•acamprosate has many molecular effects including
actions on GABA, glutamate, serotonergic,
noradrenergic, and dopaminergic receptors
•weak NMDA-receptor antagonist and a GABAA-R
activator
•widely distributed and is eliminated renally.
•It does not appear to participate in drug-drug
interactions.
•The most common adverse effects are gastrointestinal
(nausea, vomiting, diarrhea) and rash.
•It should not be used in patients with severe renal
impairment.
6/6/2021 73
Other drugs
•Baclofen has shown positive results for the treatment
of AUD in some studies
•Nalmefenestructurally similar to naltrexone, is used to
treat opioid overdose. it is approved to reduce heavy
drinking.
•longer duration of action
•lack of dose-dependent liver toxicity
•higher affinity of binding to μ− and κ−opioid receptors.
•Gabapentin, which interacts with the α2δ subunit of
neuronal voltage gated Ca
2+
channels, is primarily used
to treat epileptic seizures and neuropathic pain.
•Varenicline, which is approved for smoking cessation,
also reduces alcohol consumption in preclinical and
clinical models
6/6/2021 74
•Baclofen has shown positive results for the treatment
of AUD in some studies
•Nalmefenestructurally similar to naltrexone, is used to
treat opioid overdose. it is approved to reduce heavy
drinking.
•longer duration of action
•lack of dose-dependent liver toxicity
•higher affinity of binding to μ− and κ−opioid receptors.
•Gabapentin, which interacts with the α2δ subunit of
neuronal voltage gated Ca
2+
channels, is primarily used
to treat epileptic seizures and neuropathic pain.
•Varenicline, which is approved for smoking cessation,
also reduces alcohol consumption in preclinical and
clinical models
6/6/2021 74
6/6/2021 75
Opioids and opioid-like cpds
•Opioids may have been the first drugs to be abused and are
still among the most commonly used for nonmedical
purposes
•The most commonly abused opioids include morphine,
heroin (diacetylmorphine),codeine, and oxycodone.
•Tramadol though not considered as a classic opioid acts as
an agonist on U-opioid receptors
•Methadone , fentanyl, morphine, meperidine and tramadol
are useful clinically for moderate to severe pain
•All of these drugs induce strong tolerance and dependence
6/6/2021 76
•Opioids may have been the first drugs to be abused and are
still among the most commonly used for nonmedical
purposes
•The most commonly abused opioids include morphine,
heroin (diacetylmorphine),codeine, and oxycodone.
•Tramadol though not considered as a classic opioid acts as
an agonist on U-opioid receptors
•Methadone , fentanyl, morphine, meperidine and tramadol
are useful clinically for moderate to severe pain
•All of these drugs induce strong tolerance and dependence
6/6/2021 76
Opioid Receptors
•Opioids act on G-protein coupled receptors: μ-, κ-,
and δ.
•all three receptors couple to inhibitory G
proteins(they all inhibit adenylyl cyclase) but
produce opposing effects in the CNS
•μ-opioid Receptersare expressed in GABA ergic
neurons(which they inhibit) causing disinhibition of
dopamine neurons-analgesic activity, euphoria,
sedation, depression, dependence
•κ-opioid receptors are expressed on and inhibit
dopamine neurons-dysphoria,
6/6/2021 77
•Opioids act on G-protein coupled receptors: μ-, κ-,
and δ.
•all three receptors couple to inhibitory G
proteins(they all inhibit adenylyl cyclase) but
produce opposing effects in the CNS
•μ-opioid Receptersare expressed in GABA ergic
neurons(which they inhibit) causing disinhibition of
dopamine neurons-analgesic activity, euphoria,
sedation, depression, dependence
•κ-opioid receptors are expressed on and inhibit
dopamine neurons-dysphoria,
6/6/2021 77
Tramadol
•Tramadol is almost completely absorbed after oral (>90%),
rectal and intramuscular administration.
•Average bioavailability is 70%, irrespective of food intake
•Tramadol binds with low affinity to the µ-opioid receptor
with an affinity approximately on oral 4000-fold less than
that of morphine
•Tramadol has one of the least abuse potential but can
induce abuse on prolonged administration
•In addition to its opioid activity, tramadol acts on
serotonergic and noradrenergic neurons
•a serotonin releaser and as a serotonin reuptake inhibitor,
and as a reuptake inhibitor of noradrenaline
•As an analgesic, tramadol is approximately equipotent as
codeineand has about 10% of the potency of morphine
after parenteral administration
6/6/2021 78
•Tramadol is almost completely absorbed after oral (>90%),
rectal and intramuscular administration.
•Average bioavailability is 70%, irrespective of food intake
•Tramadol binds with low affinity to the µ-opioid receptor
with an affinity approximately on oral 4000-fold less than
that of morphine
•Tramadol has one of the least abuse potential but can
induce abuse on prolonged administration
•In addition to its opioid activity, tramadol acts on
serotonergic and noradrenergic neurons
•a serotonin releaser and as a serotonin reuptake inhibitor,
and as a reuptake inhibitor of noradrenaline
•As an analgesic, tramadol is approximately equipotent as
codeineand has about 10% of the potency of morphine
after parenteral administration
6/6/2021 78
Withdrawal syndrome
•it may be very severe and includes
•intense dysphoria, nausea, vomiting, muscle aches, lacrimation,
rhinorrhea, mydriasis, piloerection, sweating, diarrhea, yawning,
restlessness, abdominal cramps, and hot flashes/chills and fever
•Some experience suicidal tendencies
•clonidine, an alpha-2 agonist, has been used to attenuate
symptoms such as anxiety, tachycardia, hypertension, chills,
and piloerection
•The relative risk of addiction is 4 out of 5
6/6/2021 79
•it may be very severe and includes
•intense dysphoria, nausea, vomiting, muscle aches, lacrimation,
rhinorrhea, mydriasis, piloerection, sweating, diarrhea, yawning,
restlessness, abdominal cramps, and hot flashes/chills and fever
•Some experience suicidal tendencies
•clonidine, an alpha-2 agonist, has been used to attenuate
symptoms such as anxiety, tachycardia, hypertension, chills,
and piloerection
•The relative risk of addiction is 4 out of 5
6/6/2021 79
Management of opioid Use Disorder
•Goals of treatment are
•reduction in dependency on the substance,
•reduction in withdrawal symptoms, and
•prevention of death from the substance
•Treatment of OUD is biphasic
•Non-pharmacologic –counselling and behavioral therapy
•pharmacologic
6/6/2021 80
•Goals of treatment are
•reduction in dependency on the substance,
•reduction in withdrawal symptoms, and
•prevention of death from the substance
•Treatment of OUD is biphasic
•Non-pharmacologic –counselling and behavioral therapy
•pharmacologic
6/6/2021 80
Pharmacotherapy of OUD
•Methadoneis a long acting mu-opioid agonist that
suppresses withdrawal symptoms and controls the
craving for opioids in maintenance therapy
•Methadoneis later tapered off eventually and has less
likelihood of inducing intense craving or withdrawal
•Naltrexone or nalmefenewhich are long acting are
have been used to maintain remission. Should be used
at least 7 days after abstinence to avoid inducing acute
withdrawal.
•Advantages of nalmefenerelative to naltrexone include
longer half-life, greater oral bioavailability, and no
observed dose-dependent liver toxicity
6/6/2021 81
•Methadoneis a long acting mu-opioid agonist that
suppresses withdrawal symptoms and controls the
craving for opioids in maintenance therapy
•Methadoneis later tapered off eventually and has less
likelihood of inducing intense craving or withdrawal
•Naltrexone or nalmefenewhich are long acting are
have been used to maintain remission. Should be used
at least 7 days after abstinence to avoid inducing acute
withdrawal.
•Advantages of nalmefenerelative to naltrexone include
longer half-life, greater oral bioavailability, and no
observed dose-dependent liver toxicity
6/6/2021 81
•Buprenorphineis a partial mu receptor agonist that
is very lipophilic and is available as buprenorphine
alone or buprenorphine/naloxone formulations
•this partial agonist activity reduces craving whiles
blocking or blunting the euphoric effects of full
agonist
6/6/2021 82
is very lipophilic and is available as buprenorphine
alone or buprenorphine/naloxone formulations
•this partial agonist activity reduces craving whiles
blocking or blunting the euphoric effects of full
agonist
6/6/2021 82
Case study
•A 27-year-old woman on buprenorphine-naloxone
(Suboxone®) for treatment of opioid dependence is
admitted to the hospital with severe abdominal pain
due to a perforated gastric ulcer. She received
hydromorphone in the ED, and is urgently taken to the
operating room.
•Postoperatively, she is on a patient-controlled
analgesic (PCA) pump containing fentanyl.
•Her last dose of buprenorphine-naloxone was 20 h
prior to the surgery; her daily dose is 16 mg.
•Question: How can Pain be Managed in Patients who
are Taking Buprenorphine-Naloxone? What
Adjustments to her Medication Regimen can be
Recommended?
6/6/2021 83
•A 27-year-old woman on buprenorphine-naloxone
(Suboxone®) for treatment of opioid dependence is
admitted to the hospital with severe abdominal pain
due to a perforated gastric ulcer. She received
hydromorphone in the ED, and is urgently taken to the
operating room.
•Postoperatively, she is on a patient-controlled
analgesic (PCA) pump containing fentanyl.
•Her last dose of buprenorphine-naloxone was 20 h
prior to the surgery; her daily dose is 16 mg.
•Question: How can Pain be Managed in Patients who
are Taking Buprenorphine-Naloxone? What
Adjustments to her Medication Regimen can be
Recommended?
6/6/2021 83
Benzodiazepines
•Any patient who has taken a benzodiazepine for
longer than 3–4 weeks is likely to have withdrawal
symptoms if the drug is ceased abruptly.
•The risk of inducing dependence can be reduced by
issuing prescriptions limited to 1–2 weeks supply.
•Benzodiazepines have powerful sedative, anxiolytic
and anticonvulsant effects,
•selectively potentiate the effects of GABA on some
GABA
Areceptors.
6/6/2021 84
•Any patient who has taken a benzodiazepine for
longer than 3–4 weeks is likely to have withdrawal
symptoms if the drug is ceased abruptly.
•The risk of inducing dependence can be reduced by
issuing prescriptions limited to 1–2 weeks supply.
•Benzodiazepines have powerful sedative, anxiolytic
and anticonvulsant effects,
•selectively potentiate the effects of GABA on some
GABA
Areceptors.
6/6/2021 84
•Benzodiazepines are mostly abused for their
euphoriant effects, but most often abuse occurs
concomitant with other drugs, (e.g, to attenuate
anxiety during withdrawal from opioids).
•Benzodiazepine is one of the most co-abused drugs and
is rarely abused alone
•Examples of benzodiazepines include;
•ultra-short acting (midazolam, zolpidem),
•short acting (lorazepam, oxazepam, temazepam),
•medium acting (alprazolam, nitrazepam), and
•long acting (Diazepam, chlordiazepoxide, flurazepam,
clonazepam)
6/6/2021 85
euphoriant effects, but most often abuse occurs
concomitant with other drugs, (e.g, to attenuate
anxiety during withdrawal from opioids).
•Benzodiazepine is one of the most co-abused drugs and
is rarely abused alone
•Examples of benzodiazepines include;
•ultra-short acting (midazolam, zolpidem),
•short acting (lorazepam, oxazepam, temazepam),
•medium acting (alprazolam, nitrazepam), and
•long acting (Diazepam, chlordiazepoxide, flurazepam,
clonazepam)
6/6/2021 85
Benzodiazepines
•Withdrawal from benzodiazepines occurs within days of
stopping the medication and varies with the duration of
action of the drug
•Insomnia
•Restlessness, agitation or paranoia
•Severe headache
•Manic disorders
•Perceptual distortions (e.g. feelings of being surrounded by cotton
wool)
•visual and auditory hallucinations, paranoia, feelings of unreality
•Depersonalization
•Paraesthesiae
•sweating, muscle cramps and muscle twitches
•Few experience seizures or life threatening conditions
6/6/2021 86
•Withdrawal from benzodiazepines occurs within days of
stopping the medication and varies with the duration of
action of the drug
•Insomnia
•Restlessness, agitation or paranoia
•Severe headache
•Manic disorders
•Perceptual distortions (e.g. feelings of being surrounded by cotton
wool)
•visual and auditory hallucinations, paranoia, feelings of unreality
•Depersonalization
•Paraesthesiae
•sweating, muscle cramps and muscle twitches
•Few experience seizures or life threatening conditions
6/6/2021 86
6/6/2021 87
Management of BUD
•These range from 25% at 12 months for those with
complicated dependence.15 to 80% for older adults in
general practice
•Abrupt cessation of benzodiazepines after a period of 1–6
months of use can cause life-threatening seizures so the
dose should be gradually reduced.
•Substitute shorter duration with longer acting then
gradually tapper off
•The duration of weaning depends on tolerability and the
starting dose.
•Gradual withdrawal over at least 10 weeks is successful in
achieving long-term abstinence
6/6/2021 88
•These range from 25% at 12 months for those with
complicated dependence.15 to 80% for older adults in
general practice
•Abrupt cessation of benzodiazepines after a period of 1–6
months of use can cause life-threatening seizures so the
dose should be gradually reduced.
•Substitute shorter duration with longer acting then
gradually tapper off
•The duration of weaning depends on tolerability and the
starting dose.
•Gradual withdrawal over at least 10 weeks is successful in
achieving long-term abstinence
6/6/2021 88
PHARMACOTHERAPY
•Anticonvulsants have some efficacy in benzodiazepine withdrawal
if the patient is not dependent on other drugs. Carbamazepine
has a modest benefit12 and pregabalin can be effective.
•Flumazenil, a GABA
Areceptor antagonist, has been used as a low-
dose intravenous or subcutaneous infusion over four days to help
patients rapidly withdraw from benzodiazepines to a lower dose
or to abstinence without significant withdrawal symptoms
Psychotherapy
•A meta-analysis of treatment for benzodiazepine discontinuation
found that gradual dose reduction combined with psychological
treatment was superior to gradual dose reduction alone.
6/6/2021 89
•Anticonvulsants have some efficacy in benzodiazepine withdrawal
if the patient is not dependent on other drugs. Carbamazepine
has a modest benefit12 and pregabalin can be effective.
•Flumazenil, a GABA
Areceptor antagonist, has been used as a low-
dose intravenous or subcutaneous infusion over four days to help
patients rapidly withdraw from benzodiazepines to a lower dose
or to abstinence without significant withdrawal symptoms
Psychotherapy
•A meta-analysis of treatment for benzodiazepine discontinuation
found that gradual dose reduction combined with psychological
treatment was superior to gradual dose reduction alone.
6/6/2021 89
Barbiturates
•High addictive potential, overdose risk, and narrow
therapeutic range
•Barbiturates enhance the activity of GABA, a
neurotransmitter
•Barbiturates toxicity constitute respiratory depression,
generalized seizures, ataxia, altered consciousness,
slurred speech, Lack of balance/vertigo etc
•Restlessness, Anxiety, Tremors, Low body temperature,
Sweating, Insomnia, Anxiety, Seizures
•Management of barbiturate withdrawal and addiction
is similar to that of benzodiazepines.
6/6/2021 90
•High addictive potential, overdose risk, and narrow
therapeutic range
•Barbiturates enhance the activity of GABA, a
neurotransmitter
•Barbiturates toxicity constitute respiratory depression,
generalized seizures, ataxia, altered consciousness,
slurred speech, Lack of balance/vertigo etc
•Restlessness, Anxiety, Tremors, Low body temperature,
Sweating, Insomnia, Anxiety, Seizures
•Management of barbiturate withdrawal and addiction
is similar to that of benzodiazepines.
6/6/2021 90
Barbiturates
•Though not as readily available as they once were,
some barbiturates continue to be abused for their
sedating high that includes effects such as:
•Relaxation.
•Drowsiness.
•Euphoria.
•Disinhibition.
•Phenobarbital, Amobarbital (Amytal), Secobarbital
(Seconal), Butalbital and thiopental
•Tolerance with physical and psychological
dependence occur after chronic administration
6/6/2021 91
•Though not as readily available as they once were,
some barbiturates continue to be abused for their
sedating high that includes effects such as:
•Relaxation.
•Drowsiness.
•Euphoria.
•Disinhibition.
•Phenobarbital, Amobarbital (Amytal), Secobarbital
(Seconal), Butalbital and thiopental
•Tolerance with physical and psychological
dependence occur after chronic administration
6/6/2021 91
Withdrawal
•Increased sweating.
•Quickened heart rate –
greater than 100 beats
per minute.
•Quickened breathing
rate.
•Raised blood pressure.
•Increased body
temperature.
•Hallucinations.
•Sped-up movements.
•Anxiety.
•Panic.
•Shaky hands.
•Grand mal seizures.
•Inability to sleep.
•Nausea and vomiting.
6/6/2021 92
•Increased sweating.
•Quickened heart rate –
greater than 100 beats
per minute.
•Quickened breathing
rate.
•Raised blood pressure.
•Increased body
temperature.
•Hallucinations.
•Sped-up movements.
•Anxiety.
•Panic.
•Shaky hands.
•Grand mal seizures.
•Inability to sleep.
•Nausea and vomiting.
6/6/2021 92
Management of Barbiturate Use
Disorder
•Gradually reduce and slowly taper the dose of
barbiturates over a length of time,
•End use completely while providing medical
assistance to ensure comfort and safety
6/6/2021 93
Disorder
•Gradually reduce and slowly taper the dose of
barbiturates over a length of time,
•End use completely while providing medical
assistance to ensure comfort and safety
6/6/2021 93
Barbiturates and Other Drug Use
•Amplify the euphoric effect
•Increase the anti-anxiety effects
•Offset the unwanted effects of a stimulant
substance.
•NB rule out other co abused drugs
6/6/2021 94
•Amplify the euphoric effect
•Increase the anti-anxiety effects
•Offset the unwanted effects of a stimulant
substance.
•NB rule out other co abused drugs
6/6/2021 94
CNS STIMULANTS
6/6/2021 95
6/6/2021 95
OVERVIEW
•CNS SIMULANTS
•CONVULSANTS –strychnine, picrotoxin, bicuculine
•ANALEPTICS –doxapram
•PSYCHOSTIMULANTS
•PSCHOMOTORSTIMULANTS
•PSYCHEDELIC/PSYCHOTOMIMETIC STIMULANTS
•PSYCHOMOTORSTIMULANTS
•Cocaine
•Amphetamines
•Nicotine
•Caffeine
•PSYCHEDELIC/HALLUCINOGENIC DRUGS
•Methylenedioxymethamphetamine (MDMA, "ecstasy")
•Lysergic acid diethylamide (LSD)
•Phencyclidine (PCP) and
•Ketamine
•CNS SIMULANTS
•CONVULSANTS –strychnine, picrotoxin, bicuculine
•ANALEPTICS –doxapram
•PSYCHOSTIMULANTS
•PSCHOMOTORSTIMULANTS
•PSYCHEDELIC/PSYCHOTOMIMETIC STIMULANTS
•PSYCHOMOTORSTIMULANTS
•Cocaine
•Amphetamines
•Nicotine
•Caffeine
•PSYCHEDELIC/HALLUCINOGENIC DRUGS
•Methylenedioxymethamphetamine (MDMA, "ecstasy")
•Lysergic acid diethylamide (LSD)
•Phencyclidine (PCP) and
•Ketamine
Psychostimulants
•Drugs in this category have a marked effect on mental
function and behavior, producing excitement and
euphoria, reduced sensation of fatigue and an increase in
motor activity.
•Associated with sustained lose of appetite and wasting
syndrome
•These are drugs whose primary action is to stimulate the
CNS globally or to improve specific brain functions.
•They are highly reinforcing because of the profound sense
of well-being, energy and optimism associated with it
•Tend to produce convulsions or seizures at high doses
•Psychostimulants usually are predominantly cortical in
nature than those on medullary vital centers
•Drugs in this category have a marked effect on mental
function and behavior, producing excitement and
euphoria, reduced sensation of fatigue and an increase in
motor activity.
•Associated with sustained lose of appetite and wasting
syndrome
•These are drugs whose primary action is to stimulate the
CNS globally or to improve specific brain functions.
•They are highly reinforcing because of the profound sense
of well-being, energy and optimism associated with it
•Tend to produce convulsions or seizures at high doses
•Psychostimulants usually are predominantly cortical in
nature than those on medullary vital centers
COCAINE
•The prevalence of cocaine abuse has increased greatly over
the last decade and now represents a major public health
problem worldwide.
•Cocaine is found in the leaves of a South American shrub,
coca (Erythroxylon coca)
•Cocaine drives a multi-trillion dollar industry worldwide
•It’s a major public Health Concern since its use is connected
to criminality of heinous magnitude
•Twice more men are addicted than women
•The prevalence of cocaine abuse has increased greatly over
the last decade and now represents a major public health
problem worldwide.
•Cocaine is found in the leaves of a South American shrub,
coca (Erythroxylon coca)
•Cocaine drives a multi-trillion dollar industry worldwide
•It’s a major public Health Concern since its use is connected
to criminality of heinous magnitude
•Twice more men are addicted than women
SHORT TERM EFFECTS
•Elevated Blood pressure
•Pin point Pupils
•Improve attention
•Bradycardia
•Increased heart rate
/tachycardia
•Increased energy
•Improved attention and
alerteness
•Increased respiratory
rate.
•decreased need for sleep
or insomnia
•Reduced appetite
•improved confidence
and concentrations
•Hallucinations
•Delusions
•Poor judgment and
decision-making
6/6/2021 99
•Elevated Blood pressure
•Pin point Pupils
•Improve attention
•Bradycardia
•Increased heart rate
/tachycardia
•Increased energy
•Improved attention and
alerteness
•Increased respiratory
rate.
•decreased need for sleep
or insomnia
•Reduced appetite
•improved confidence
and concentrations
•Hallucinations
•Delusions
•Poor judgment and
decision-making
6/6/2021 99
LONG TERM EFFECTS
•Anxiety
•Depression
•Mood swings
•Anger/aggressiveness
•Increased confidence
•Insomnia
•Anxiety
•Depression
•Mood swings
•Anger/aggressiveness
•Increased confidence
•Hyperthermia
•Tachycardia/arrthymias
•Seizures
•Weight loss
6/6/2021 100
•Anxiety
•Depression
•Mood swings
•Anger/aggressiveness
•Increased confidence
•Insomnia
•Anxiety
•Depression
•Mood swings
•Anger/aggressiveness
•Increased confidence
•Hyperthermia
•Tachycardia/arrthymias
•Seizures
•Weight loss
6/6/2021 100
Withdrawal include
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Amphetamines and Related Agents
1.Amphetamine
2.Dextroamphetamine,
3.Methamphetamine,
4.Methylphenidate
5.Fenfluramine
1.Amphetamine
2.Dextroamphetamine,
3.Methamphetamine,
4.Methylphenidate
5.Fenfluramine
Pharmacokinetics
•Oral bioavailablityof 75-100%
•20% protein Binding
•Eliminated via renal route but small portion is
Metabolisedby CYP2D6.
•Onset of action between 30-60min with
elimination half life of 9-11hrs
•Readily absorbed from the gastrointestinal
tract, and freely penetrates the blood-brain
and placental barriers.
•Oral bioavailablityof 75-100%
•20% protein Binding
•Eliminated via renal route but small portion is
Metabolisedby CYP2D6.
•Onset of action between 30-60min with
elimination half life of 9-11hrs
•Readily absorbed from the gastrointestinal
tract, and freely penetrates the blood-brain
and placental barriers.
Mechanism of action
•The amphetamines act by releasing monoamines, primarily
dopamine and noradrenaline (less so 5HT ), from nerve terminals
in the brain
•They also displace the catecholamines from vesicular storage and
enhance passive diffusion of NT from Nerve terminals into
synaptic cleft
•Amphetamines compete with DA and NE for DAT and NET
respectively
•At high concentrations amphetamines can inhibit monoamine
oxidase
All of the above will combine to increase the concentration of
extracellular dopamine and noradrenaline in the vicinity of the
synapse
•The amphetamines act by releasing monoamines, primarily
dopamine and noradrenaline (less so 5HT ), from nerve terminals
in the brain
•They also displace the catecholamines from vesicular storage and
enhance passive diffusion of NT from Nerve terminals into
synaptic cleft
•Amphetamines compete with DA and NE for DAT and NET
respectively
•At high concentrations amphetamines can inhibit monoamine
oxidase
All of the above will combine to increase the concentration of
extracellular dopamine and noradrenaline in the vicinity of the
synapse
Pharmacological effects
Effects
•The main central effects of amphetamine-like drugs
are:
•locomotor stimulation
•euphoria and excitement
•stereotyped behavior
•Anorexia
•Amphetamines have peripheral sympathomimetic
actions producing a rise in blood pressure and
inhibition of gastrointestinal motility
Effects
•The main central effects of amphetamine-like drugs
are:
•locomotor stimulation
•euphoria and excitement
•stereotyped behavior
•Anorexia
•Amphetamines have peripheral sympathomimetic
actions producing a rise in blood pressure and
inhibition of gastrointestinal motility
Clinical uses
•The main use of amphetamines is in the
treatment of Attention Deficit Hyperactivity
Disorder (ADHD), occurring in up to 9 % of
children
•Pharmacotherapy of Narcolepsy
•Appetite suppressant. Amphetamines reduce
appetite, but are no longer used for this
purpose.
•The main use of amphetamines is in the
treatment of Attention Deficit Hyperactivity
Disorder (ADHD), occurring in up to 9 % of
children
•Pharmacotherapy of Narcolepsy
•Appetite suppressant. Amphetamines reduce
appetite, but are no longer used for this
purpose.
Toxicity
CNS
•Tactile hallucinations, such as formication
•mentally instability, psychosis (schizophrenia) and aggression
•Emotional instability, suicidal tendency, chronic depression and
anhedonia
Cardiovascular
•hypertension, stroke, seizures, cardiac arrhythmias and
cardiomyopathies, myocardial infarction, and malnutrition
Other organ systems
•hyperthermia, sexual dysfunction, dental caries, rhabdomyolysis,
renal failure,
CNS
•Tactile hallucinations, such as formication
•mentally instability, psychosis (schizophrenia) and aggression
•Emotional instability, suicidal tendency, chronic depression and
anhedonia
Cardiovascular
•hypertension, stroke, seizures, cardiac arrhythmias and
cardiomyopathies, myocardial infarction, and malnutrition
Other organ systems
•hyperthermia, sexual dysfunction, dental caries, rhabdomyolysis,
renal failure,
Tolerance, Dependence and withdrawal
•Tolerance to the stimulant effects develops rapidly, although
peripheral sympathomimetic effects may persist.
•Amphetamines induce strong psychological dependence.
•Stimulant effect lasts for a few hours and is followed by depression
and anxiety.
•Dependence on amphetamine appears to be a consequence of the
unpleasant after-effect that it produces, and the insistent memory of
euphoria, which leads to a desire for a repeated dose
•There is no clear-cut physical withdrawal syndrome such as occurs
with opiates.
•The combination o tachyphylaxis and allostasis makes discontinuation
o stimulants particularly difficult for addicts, both in the short and
long term.
•Tolerance to the stimulant effects develops rapidly, although
peripheral sympathomimetic effects may persist.
•Amphetamines induce strong psychological dependence.
•Stimulant effect lasts for a few hours and is followed by depression
and anxiety.
•Dependence on amphetamine appears to be a consequence of the
unpleasant after-effect that it produces, and the insistent memory of
euphoria, which leads to a desire for a repeated dose
•There is no clear-cut physical withdrawal syndrome such as occurs
with opiates.
•The combination o tachyphylaxis and allostasis makes discontinuation
o stimulants particularly difficult for addicts, both in the short and
long term.
Clinical management of addiction
•Psychological Dependence with little or insignificant physiological
dependence
•Clinical depression can be managed with Benzodiazepines
•Psychological Dependence with little or insignificant physiological
dependence
•Clinical depression can be managed with Benzodiazepines
PSYCHEDELIC/HALLUCINOGENIC DRUGS
•They are drugs that have as their primary effect the
production of disturbances of perception, thought, or mood
at low doses with minimal effects on memory and
orientation.
•The main effects of these drugs are on mental function,
most notably an alteration of perception in such a way that
sights and sounds appear distorted and fantastic.
•They appear to predominately act as agonists or partial
agonists at serotonin (5-HT) receptors, specifically the 5-HT
2
receptor
•Hallucinogenic properties is mediated by 5HT
2Areceptor–
mediated disruption of thalamic gating with sensory
overload of the cortex
•They are drugs that have as their primary effect the
production of disturbances of perception, thought, or mood
at low doses with minimal effects on memory and
orientation.
•The main effects of these drugs are on mental function,
most notably an alteration of perception in such a way that
sights and sounds appear distorted and fantastic.
•They appear to predominately act as agonists or partial
agonists at serotonin (5-HT) receptors, specifically the 5-HT
2
receptor
•Hallucinogenic properties is mediated by 5HT
2Areceptor–
mediated disruption of thalamic gating with sensory
overload of the cortex
Psychedelics…
There are two main categories of psychedelic compound
•Indoleamines/tryptamines
•Lysergic acid diethylamide(LSD)
•Dimethyltryptamine (DMT)
•Psilocybin
•Phenethylamines
•Mescaline ,
•Dimethoxymethylamphetamine(DOM),
•Methylenedioxyamphetamine(MDA)
•Methylenedioxymethamphetamine (MDMA, "ecstasy")
•All groups have a relatively high affinity for serotonin 5-
HT
2receptors but they differ in their affinity for other
subtypes of 5-HT receptors
There are two main categories of psychedelic compound
•Indoleamines/tryptamines
•Lysergic acid diethylamide(LSD)
•Dimethyltryptamine (DMT)
•Psilocybin
•Phenethylamines
•Mescaline ,
•Dimethoxymethylamphetamine(DOM),
•Methylenedioxyamphetamine(MDA)
•Methylenedioxymethamphetamine (MDMA, "ecstasy")
•All groups have a relatively high affinity for serotonin 5-
HT
2receptors but they differ in their affinity for other
subtypes of 5-HT receptors
Lysergic acid diethylamide(LSD)
•is a semisynthetic product of lysergic acid, a natural substance from
the parasitic rye fungus Claviceps purpurea
•LSD is the most famous and exceptionally potent psychotomimetic
drug capable of producing strong effects in humans in doses less than
1 μg/kg.
•The effects of hallucinogenic drugs are variable, even in the same
individual on different occasions
•LSD is absorbed rapidly after oral administration.
•Pharmacological effects are observed between 40–60 min, peaking at
2–4 h and gradually returning to baseline over 6–8 h
•The distribution of LSD across tissue and organ systems is yet to be
quantified for the human organism
•is a semisynthetic product of lysergic acid, a natural substance from
the parasitic rye fungus Claviceps purpurea
•LSD is the most famous and exceptionally potent psychotomimetic
drug capable of producing strong effects in humans in doses less than
1 μg/kg.
•The effects of hallucinogenic drugs are variable, even in the same
individual on different occasions
•LSD is absorbed rapidly after oral administration.
•Pharmacological effects are observed between 40–60 min, peaking at
2–4 h and gradually returning to baseline over 6–8 h
•The distribution of LSD across tissue and organ systems is yet to be
quantified for the human organism
Lysergic acid diethylamide(LSD)
•The main molecular target of LSD and other hallucinogens is
the 5-HT
2Areceptor.
•This receptor couples to G proteins of the G
qtype and
generates inositol trisphosphate (IP3), leading to a release of
intracellular calcium
•it activates the signal transduction enzyme phospholipase
A
2
•it is thought that it works by increasing glutamate release in
the cerebral cortex
•It inhibits the firing of 5-HT-containing neurons in the raphe
nuclei apparently by acting as an agonist on the inhibitory
auto receptors of these cells.
•The main molecular target of LSD and other hallucinogens is
the 5-HT
2Areceptor.
•This receptor couples to G proteins of the G
qtype and
generates inositol trisphosphate (IP3), leading to a release of
intracellular calcium
•it activates the signal transduction enzyme phospholipase
A
2
•it is thought that it works by increasing glutamate release in
the cerebral cortex
•It inhibits the firing of 5-HT-containing neurons in the raphe
nuclei apparently by acting as an agonist on the inhibitory
auto receptors of these cells.
Lysergic acid diethylamide(LSD)
•A moderate dose (75–150 μgp.o.) of LSD will significantly
alter state of consciousness
•Hallucinations–visual, auditory, tactile or olfactory –also occur, and
sensory modalities may become confused, so that sounds are
perceived as visions
•Thought processes tend to become illogical and disconnected
•Sympathetic stimulation is evidenced, by a pupillary dilation and
light to moderate increases in heart rate and blood pressure
•Other symptoms point to parasympathetic stimulation:
•Diaphoresis, salivation, nausea may occur,
•emesis is exceptional and flushing of the face is more frequent
•Visual effects are prominent. Colors seem more intense, and shapes
may appear altered. The subject may focus attention on unusual
items such as the pattern of hairs on the back of the hand.
•A moderate dose (75–150 μgp.o.) of LSD will significantly
alter state of consciousness
•Hallucinations–visual, auditory, tactile or olfactory –also occur, and
sensory modalities may become confused, so that sounds are
perceived as visions
•Thought processes tend to become illogical and disconnected
•Sympathetic stimulation is evidenced, by a pupillary dilation and
light to moderate increases in heart rate and blood pressure
•Other symptoms point to parasympathetic stimulation:
•Diaphoresis, salivation, nausea may occur,
•emesis is exceptional and flushing of the face is more frequent
•Visual effects are prominent. Colors seem more intense, and shapes
may appear altered. The subject may focus attention on unusual
items such as the pattern of hairs on the back of the hand.
Tolerance &Dependence
•Tolerance does develop to the behavioral effects of LSD after
three to four daily doses, but no withdrawal syndrome has
been observed
•Dependence and addiction do not occur and so do not
require medical management.
•Behavioral therapy is however essential in alleviating anxiety
and panic associated with a “bad trip”
•Tolerance does develop to the behavioral effects of LSD after
three to four daily doses, but no withdrawal syndrome has
been observed
•Dependence and addiction do not occur and so do not
require medical management.
•Behavioral therapy is however essential in alleviating anxiety
and panic associated with a “bad trip”
Endocannabinoids
Other endogenous mediators
mimic the effects of THC and
CBD.
Anandamide
2-arachidonoyl glycerol
have been identified as
agonist at CB-R but with
varying affinity and efficiency
at the Receptors
Other endogenous mediators
mimic the effects of THC and
CBD.
Anandamide
2-arachidonoyl glycerol
have been identified as
agonist at CB-R but with
varying affinity and efficiency
at the Receptors
Pharmacokinetics
•The UNODC states that
•cannabis often contains 5% THC content,
•resin "can contain up to 20% THC content", and that
•Cannabis oil may contain more than 60% THC content
•The effect of cannabis, taken by smoking, takes about 1 hrto develop
fully and lasts for 2–3 h.
•It is inactivated by conjugation and its metabolites undergo extensive
enterohepatic recirculation
•Most cannabinoids are lipophilic compounds that are easily stored in fat,
thus yielding a long elimination half-life relative to other recreational
drugs
•It is usually detected several weeks after last use
•Cannabis is often considered as a “gateway drug”
•Users often progress to use harder or more stimulating drugs
•The UNODC states that
•cannabis often contains 5% THC content,
•resin "can contain up to 20% THC content", and that
•Cannabis oil may contain more than 60% THC content
•The effect of cannabis, taken by smoking, takes about 1 hrto develop
fully and lasts for 2–3 h.
•It is inactivated by conjugation and its metabolites undergo extensive
enterohepatic recirculation
•Most cannabinoids are lipophilic compounds that are easily stored in fat,
thus yielding a long elimination half-life relative to other recreational
drugs
•It is usually detected several weeks after last use
•Cannabis is often considered as a “gateway drug”
•Users often progress to use harder or more stimulating drugs
Medicinal uses
There is evidence supporting the use of cannabis or
its derivatives in the treatment of
•chemotherapy-induced nausea and vomiting,
•Appetite stimulation
•neuropathic pain
•multiple sclerosis.
•Movement disorders ( Parkinson's, Parkinson disease,
Huntington disease, Tourette syndrome)
Lower levels of evidence support its use for
•AIDS wasting syndrome,
•Anti-convulsant in epileptic seizures or
•rheumatoid arthritis,
•glaucoma
There is evidence supporting the use of cannabis or
its derivatives in the treatment of
•chemotherapy-induced nausea and vomiting,
•Appetite stimulation
•neuropathic pain
•multiple sclerosis.
•Movement disorders ( Parkinson's, Parkinson disease,
Huntington disease, Tourette syndrome)
Lower levels of evidence support its use for
•AIDS wasting syndrome,
•Anti-convulsant in epileptic seizures or
•rheumatoid arthritis,
•glaucoma
Pharmacological effects
•Sensations of relaxation and well-being
•Feelings of sharpened sensory awareness
•Central effects include
•impairment of short-term memory and simple, learning tasks –
subjective feelings of confidence and heightened creativity are not
reflected in actual performance
•impairment of motor coordination (e.g. driving performance)
•catalepsy ,hypothermia , analgesia, anti-emesis and increased
appetite
•Others
•unsubstantiated claims of increased pleasure from sex (associated
with sexual offenses
•Sensations of relaxation and well-being
•Feelings of sharpened sensory awareness
•Central effects include
•impairment of short-term memory and simple, learning tasks –
subjective feelings of confidence and heightened creativity are not
reflected in actual performance
•impairment of motor coordination (e.g. driving performance)
•catalepsy ,hypothermia , analgesia, anti-emesis and increased
appetite
•Others
•unsubstantiated claims of increased pleasure from sex (associated
with sexual offenses
Peripheral effects include
•Bronchodilation, reduction in Intra Ocular Pressure,
Tachycardia
•Generalizedvasodilation of vascular or capillary beds
•Vasodilatation, which is particularly marked in superficial
blood vessels of the eye (scleral and conjunctival vessels),
producing a bloodshot appearance which is characteristic of
cannabis smokers
•Bronchodilation, reduction in Intra Ocular Pressure,
Tachycardia
•Generalizedvasodilation of vascular or capillary beds
•Vasodilatation, which is particularly marked in superficial
blood vessels of the eye (scleral and conjunctival vessels),
producing a bloodshot appearance which is characteristic of
cannabis smokers
MECHANISM OF ACTION
•Cannabinoids act via two G protein-coupled receptors (G
i/o)main
receptors; CB-1 and CB-2
•CB-1 receptors are mainly found in the CNS whilst CB-2 are distributed in
the PNS
•Most of the observed psychotomimetic actions of cannabinoids are via
CB-1
•CB1 receptors are abundant in the brain, with similar numbers to
receptors for glutamate and GABA
•Concentrated in the hippocampus -relevant to effects of cannabinoids on memory
•cerebellum-relevant to loss of Co-ordination,
•hypothalamus -important in control of appetite and body temperature,
•Substantia nigra, mesolimbic dopamine pathways -that have been implicated in
psychological ‘reward’
•Cannabinoids act via two G protein-coupled receptors (G
i/o)main
receptors; CB-1 and CB-2
•CB-1 receptors are mainly found in the CNS whilst CB-2 are distributed in
the PNS
•Most of the observed psychotomimetic actions of cannabinoids are via
CB-1
•CB1 receptors are abundant in the brain, with similar numbers to
receptors for glutamate and GABA
•Concentrated in the hippocampus -relevant to effects of cannabinoids on memory
•cerebellum-relevant to loss of Co-ordination,
•hypothalamus -important in control of appetite and body temperature,
•Substantia nigra, mesolimbic dopamine pathways -that have been implicated in
psychological ‘reward’
CB-2 are located mainly in lymphoid tissues (spleen, tonsils and
thymus) as well as circulating lymphocytes, monocytes and tissue mast
cells).
•CB-2 receptors are also present on microglia –immune cells in the
CNS which when activated contribute to chronic pain
•The localization of CB-2 receptors on cells of the immune system was
unexpected, but may account for inhibitory effects of cannabis on
immune function
•CB-2 R are coupled to AC, GIRK, MAP-K but not VOC
NB
•cannabinoids exhibit analgesic actions and activate G proteins in
the brain of CB1 knockout mice despite the absence of CB1
receptors
thymus) as well as circulating lymphocytes, monocytes and tissue mast
cells).
•CB-2 receptors are also present on microglia –immune cells in the
CNS which when activated contribute to chronic pain
•The localization of CB-2 receptors on cells of the immune system was
unexpected, but may account for inhibitory effects of cannabis on
immune function
•CB-2 R are coupled to AC, GIRK, MAP-K but not VOC
NB
•cannabinoids exhibit analgesic actions and activate G proteins in
the brain of CB1 knockout mice despite the absence of CB1
receptors
MECHANISM OF
ACTION
ACTION
•Cannabinoid receptors inhibit neurotransmission via
•Inhibition of Adenylyl Cyclase (AC) reducing cAMP levels
•Enhancing efflux of K
+
Via GIRK (G protein sensitive inward Rectifying K+
channel) to cause hyperpolarization
•Inhibits VOC(Voltage Gated Calcium Channel) directly or via its inhibition of
AC to prevent influx of calcium into neuronal ending
•CB receptors influence gene expression,
•directly by activating mitogen-activated protein kinase(MAP-K),
•Indirectly by reducing the activity of PK-A as a result of reduced adenylyl
cyclase activity
•CB1 receptors are also expressed in peripheral tissues, i.eon
endothelial cells, adipocytes and peripheral nerves where they
promote lipogenesis
•Inhibition of Adenylyl Cyclase (AC) reducing cAMP levels
•Enhancing efflux of K
+
Via GIRK (G protein sensitive inward Rectifying K+
channel) to cause hyperpolarization
•Inhibits VOC(Voltage Gated Calcium Channel) directly or via its inhibition of
AC to prevent influx of calcium into neuronal ending
•CB receptors influence gene expression,
•directly by activating mitogen-activated protein kinase(MAP-K),
•Indirectly by reducing the activity of PK-A as a result of reduced adenylyl
cyclase activity
•CB1 receptors are also expressed in peripheral tissues, i.eon
endothelial cells, adipocytes and peripheral nerves where they
promote lipogenesis
Adverse effects
User may experience
•tachycardia (possibly palpitations), mild
•diaphoresis, conjunctival injection (“red eye”), drying of the mouth,
weakness, postural
•hypotension, periods of tremulousness, incoordination, and ataxia
•Paradoxical Cannabinoid hyperemesis syndrome among some users
•Amotivational syndrome
•Acute intoxication is very rare and usually does not need treatment
because of its wide safety window
•anxiety, paranoia, and panic attacks
•Severe panic attacks or paranoia that do not resolve with behavioral
therapy can be treated with Benzodiazepines
User may experience
•tachycardia (possibly palpitations), mild
•diaphoresis, conjunctival injection (“red eye”), drying of the mouth,
weakness, postural
•hypotension, periods of tremulousness, incoordination, and ataxia
•Paradoxical Cannabinoid hyperemesis syndrome among some users
•Amotivational syndrome
•Acute intoxication is very rare and usually does not need treatment
because of its wide safety window
•anxiety, paranoia, and panic attacks
•Severe panic attacks or paranoia that do not resolve with behavioral
therapy can be treated with Benzodiazepines
TOLERANCE AND DEPENDENCE
•Psychological dependence does occur with cannabis, but it is less
compelling than with the major drugs of addiction
•A physical dependence syndrome has been reported for cannabis,
but only after extremely heavy and frequent intake.
•Tolerance to most of the effects of marijuana can develop rapidly
after only a few doses, but also disappears rapidly
•The withdrawal syndrome can
•involve anxiety, depression, irritability, restlessness, anorexia, insomnia and
vivid or disturbing dreams, sweating, tremor, nausea, vomiting, and diarrhea
•Treatment of CUD most often centers around psychosocial or
behavioral interventions
•Psychological dependence does occur with cannabis, but it is less
compelling than with the major drugs of addiction
•A physical dependence syndrome has been reported for cannabis,
but only after extremely heavy and frequent intake.
•Tolerance to most of the effects of marijuana can develop rapidly
after only a few doses, but also disappears rapidly
•The withdrawal syndrome can
•involve anxiety, depression, irritability, restlessness, anorexia, insomnia and
vivid or disturbing dreams, sweating, tremor, nausea, vomiting, and diarrhea
•Treatment of CUD most often centers around psychosocial or
behavioral interventions
Tobacco
•Tobacco is a detrimental substance, and its use dramatically
increases a person’s odds of dependence, disease, disability,
and death
•Cigarettes are the only marketed consumable product that
when used as intended will contribute to the death of half or
more of its users
•Tobacco is the primary known preventable cause of
premature death and disease in our society
•Nicotine (Nicotiana tabacum) is one of the few natural
alkaloids that exist in the liquid state. It is the active
ingredient in tobacco
•Tobacco is a detrimental substance, and its use dramatically
increases a person’s odds of dependence, disease, disability,
and death
•Cigarettes are the only marketed consumable product that
when used as intended will contribute to the death of half or
more of its users
•Tobacco is the primary known preventable cause of
premature death and disease in our society
•Nicotine (Nicotiana tabacum) is one of the few natural
alkaloids that exist in the liquid state. It is the active
ingredient in tobacco
•It is distributed quickly through the bloodstream and
crosses the blood–brain barrier reaching the brain
within 10–20 seconds after inhalation.
•The elimination half-life of nicotine in the body is
around two hours
•Cotinine is an active metabolite of nicotine that remains
in the blood with a half-life of 18–20 hours, making it
easier to analyze
•Forms
•smokeless tobacco (chewing tobacco, oral snuff)
•pipes, cigars, clove cigarettes, bidis, and hookah
•E cigars
•Nicotine patch
crosses the blood–brain barrier reaching the brain
within 10–20 seconds after inhalation.
•The elimination half-life of nicotine in the body is
around two hours
•Cotinine is an active metabolite of nicotine that remains
in the blood with a half-life of 18–20 hours, making it
easier to analyze
•Forms
•smokeless tobacco (chewing tobacco, oral snuff)
•pipes, cigars, clove cigarettes, bidis, and hookah
•E cigars
•Nicotine patch
•Nicotine has a higher affinity for nicotinic receptors in the brain than
those in skeletal muscle
•Nicotine stimulates the release of induces the release of dopamine in
the nACand acetyl choline or norepinephrine in amygdala
•Nicotine also appears to induce the release of endogenous opioids
that activate opioid pathways in the reward system.
•At high doses it can induce contractions and respiratory paralysis
•Chronic administration of nicotine has been shown to increase the
number of nicotine receptors in specific regions of the brain.
•This may represent upregulation in response to nicotine-mediated
desensitization of the receptors
those in skeletal muscle
•Nicotine stimulates the release of induces the release of dopamine in
the nACand acetyl choline or norepinephrine in amygdala
•Nicotine also appears to induce the release of endogenous opioids
that activate opioid pathways in the reward system.
•At high doses it can induce contractions and respiratory paralysis
•Chronic administration of nicotine has been shown to increase the
number of nicotine receptors in specific regions of the brain.
•This may represent upregulation in response to nicotine-mediated
desensitization of the receptors
Dependence and tolerance and
withdrawal
•Users regain sensitivity to the effects of nicotine after overnight
abstinence from nicotine
•After smoking the first cigarette of the day, the smoker experiences
marked pharmacologic effects, particularly arousal.
•Later cigarettes produces only limited pleasure or arousal and
alleviates nicotine withdrawal symptoms
•Lack of exposure to nicotine overnight results in resensitizationof
drug responses
withdrawal
•Users regain sensitivity to the effects of nicotine after overnight
abstinence from nicotine
•After smoking the first cigarette of the day, the smoker experiences
marked pharmacologic effects, particularly arousal.
•Later cigarettes produces only limited pleasure or arousal and
alleviates nicotine withdrawal symptoms
•Lack of exposure to nicotine overnight results in resensitizationof
drug responses
Withdrawal signs
•Typically manifest within a few days after quitting,
peak within a week, and subside within 2 to 4
weeks
•Anger
•Anxiety
•Depression
•Difficulty concentrating
•impatience
•Insomnia
•restlessness
•Typically manifest within a few days after quitting,
peak within a week, and subside within 2 to 4
weeks
•Anger
•Anxiety
•Depression
•Difficulty concentrating
•impatience
•Insomnia
•restlessness
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