inappropriate and usually excessive selfadministration of a psychoactive drug for nonmedical purposes Almost all abused drugs exert their effects in the CNS causing euphoria or alter perception ID: 918434
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Slide1
Drug Abuse
Slide2Drug abuse
is
inappropriate
and usually
excessive
,
self-administration
of a
psychoactive
drug for
non-medical purposes.
Almost all abused drugs exert
their effects in the CNS
causing
euphoria or alter perception.
Drugs
with high abuse potential
have a tendency to induce
compulsive drug-seeking behavior.
It is a major problem in Western countries
Slide3Characteristics of drug abuse include
:
1.Addiction (Psychological dependence
):
A state when drug-taking becomes
compulsive, taking precedence over other needs.
The individual becomes so obsessed with constantly obtaining and using a drug(
craving for drug
) aided by the positive reinforcing effects of drug in the CNS.
The drug becomes a primary goal and disrupts the ability to function in family, social, or work.
Any drug that
activates
the
mesolimbic
- dopamine system
is liable for addiction. This system correlates with
pleasure and reward.
It is composed of
ventral
tegmental
area
(VTA) &
nucleus
accumbens
.Its
pathway runs via the medial forebrain bundle, from the VTA in the midbrain to the nucleus
accumbens
and limbic region to the prefrontal cortex causing the positive reinforcing effects . Addictive drugs increase the release of
dopamine
in the
mesolimbic
- dopamine system .
Slide4Slide52.Dependance (Physical dependence
):
A state resulting
from chronic use
of a drug that has produced
tolerance
and so
physical symptoms of withdrawal
(
withdrawal or abstinence syndrome
)result from abrupt discontinuation or dosage reduction.
e.g
:
anexity,r
estlessness,bradycardia
&weight gain associated with tobacco abstinence.
3.Tolerance
:
The decrease in a pharmacological effect on repeated administration of the drug so there is need to increase the dose to reach the same pharmacological effect.
It is produced by use of drug over a long period ,it may be classified as:
pharmacodynamic
(tissue type) which results from either changes in receptor density (
downregulation
of receptors in the agonists) or changes in receptor sensitivity (
desensitisation
)
Slide6pharmacokinetic
(auto-induction of enzymes responsible for drug metabolism, e.g., in barbiturates).
The degree of
tolerance
is generally proportional to the
drug dose
and the
duration of use.
Cross-tolerance
:
occurs when repeated use of a drug in a given category confers tolerance not only to that drug but also to other drugs in the
same structural and mechanistic category.
Slide7Aetiology
of substance abuse
:
1-
Personal
factors
to obtain
:
a.
Euphoria, pleasure, psycho-stimulation
(energy, mood & concentration),
“
rush(
a sudden intense feeling) and
flush
”(warm feeling) effect
b.
Relaxation & well being
.
c
. Sexual arousal & increased libido
.
d
. Getting relief by drugs due to low tolerance for painful emotions
(or
to escape from reality
)
2.Cultural factors
like
Smoking, Alcoholism
&
Khat
.
3.Iatrogenic factors
particularly for sedatives & analgesics due to patient insistence or request or due to repeated prescriptions.
4.Increase availability of drugs & decre
ase in price
.
Risks of drug abuse include
:
Social & legal implications.
Individual’s health problems: bacterial infections, hepatitis B & HIV.
Drug toxicity & overdose.
Withdrawal syndromes.
Teratogenic
effects (Fetal alcohol syndrome; Small babies).
Increased incidence of premature deaths(death in the
youngs
or middle age).
Psychiatric symptoms are more closely linked to
polydrug
use.
Slide9Types of abused drugs:
Opioids
Originates
from Poppy
,
Papaver
somniferum
L.
,which
is an
annual herb
native to Southeastern Europe and western Asia.
Acts on
µ,
κ
,
δ
opioid
receptors.
Drugs acting
on µ receptors
are more capable of
addiction:
morphine, heroin, codeine
. µ
opioids
cause an
inhibition of
GABAergic
inhibitory
interneurons
that leads eventually to a
disinhibition
of dopamine neurons.
Their medical Use is
for
analgesia
and
anesthesia
(
fentanyl
,
oxymorphone
,
hydromorphone
, and morphine),
antitussive
(codeine,
hydromorphone
).
Dependence
– strong both
physical
and psychological
Withdrawal syndrome:
dysphoria
, nausea, muscle aches, sweating, diarrhea and fever.
opium poppy
Slide11Slide12Treatment
The
opioid
antagonists
:
naloxone
&
naltrexone
reverses the effects of a dose of morphine or heroin
within minutes
. This may
be life-saving
in the case of a
massive overdose
.
In the treatment of
opioid
addiction
, a
long-acting
opioid
(
eg
,
methadone
) is often substituted for the
shorter-actin
g, more
rewarding,
opioid
(
eg
, heroin
). For substitution therapy,
methadone is given orally once daily.
Slide132.
CNS DEPRESSANTS
Sedative/Hypnotics
Benzodiazepines
(
eg
, Diazepam,
Lorazepam
)
Benzodiazepines are
positive modulators of the GABA
A
receptor-
coupled with chloride channels & increase response to the endogenous
ligand
-GABA
.
They are commonly prescribed as
anxiolytics
and
sleep medications.
They represent a
moderate risk for abuse
, which has to be weighed against their beneficial effects.
Benzodiazepines are
abused
after their use
as hypnotics
, but may also abused after use for
treatment of withdrawal from other drugs
eg
, to attenuate anxiety during withdrawal
from
opioids
or alcohol
.
Barbiturates
Barbiturates, are now largely obsolete but were previously the most commonly abused sedative hypnotics (after ethanol).They have principally the same mechanism of action as benzodiazepines.
Slide14Both groups (
benzodiazepines
& barbiturates) may induce
psychological and physical
type of dependence & tolerance(markedly more likely, severe and earlier onset in barbiturates).
Withdrawal syndrome
: nervousness, restlessness, tremor, anxiety, confusion, dizziness, delirium, convulsions
.
Risk of acute intoxication and respiratory depression
is much greater with barbiturates.
benzodiazepines
are safer but severe cases often appear when they are
combined with alcohol
.
Slide15Alcohol (Alcoholism)
Ethano
l
is one of
the most widely abused substances in the world
..
Excessive consumption of alcoholic beverages has been linked to as many as
half of all traffic accidents
,
two-thirds
of homicides
,
three-fourths
of suicides
,
and it is a significant factor in other
crimes,
in
family problems
, and in
personal and industrial accidents.
Slide16Tolerance and dependence
:
Tolerance
:
develops over 1-3 weeks of continuing administration. There is a cross-tolerance with many anaesthetics (e.g.
halothan
)
& with benzodiazepines.
Withdrawal syndrome
: tremor, nausea, sweating, fever, occasionally hallucinations and epilepsy-like seizures.
psychological dependence
severe.
physical dependence
with prolonged heavy use.
Slide17Alcohol-related problems include
:
Social problems
: unemployment, marital problems, child abuse, financial difficulties, problems with the law, police & traffic.
Psychological & neurological problems
:
e.g.Depression
, suicide, withdrawal syndrome,
peripheral neuropathy
, cerebral
haemorrhage
,
Cerebellar
degeneration.
Sexual problems
: impotence, sterility, testicular atrophy,
gynecomastia
.
Live
r
: fatty changes, cirrhosis .
CVS
: Hypertension,
cardiomyopathy
.
GIT
:
Gastritis ,
oesophageal
varices
, cancers ,Pancreatitis.
Fetal alcohol syndrome
(
retarded growth, mental retardation and behavioural abnormalities)
Hyperuricaemia
with precipitation of gout
Vitamin deficiencies.
Slide18Treatment of alcoholism
Disulfiram
–
blockade of
aldehydedehydrogenase
acummulation
of acetaldehyde causing nausea, flushing, tachycardia, hyperventilation, panic…
Aim
: to make alcohol consumption unpleasant and intolerable
Acamprosate
– anti-craving effects.
It has structural similarity to both
glutamate and GABA
and appears to reduce the effect of excitatory amino acids such as glutamate, and modifies GABA neurotransmission.
Naloxone
– reduces alcohol-induced reward (unclear mechanism)
The drugs used to alleviate the acute abstinence syndrome: benzodiazepines,
clonidine
(inhibit
s
exaggerated neurotransmitter release) and
propranolol
(blocks excessive sympathetic activity).
Slide193.CNS Stimulants
Amphetamines
:
Amphetamines (
e.g.Amphetamine
, methamphetamine)are a group of synthetic, indirect-acting
sympathomimetic
drugs that cause the release of endogenous biogenic amines, such as dopamine
They are taken orally, sniffed
, smoked
or injected.
Amphetamines are
neurotoxic
& can cause tachycardia ,
dysrhythmias
& hypertensive crisis.
Withdrawal consists of
dysphoria
, drowsiness (in some cases, insomnia), and general irritability.
Khat
(Catha
edulis
) chewing leaves present in Yemen, Ethiopia & Somalia.
Khat
contains amphetamine-like agents (
cathine
&
cathinone
) with
psychostimulant
effects. It produces sense of well being, improvement of socialization, increase libido & increase work performance. It increases incidence of oral cancer.
Slide20Khat
leaves
Slide21Slide22Cocaine
:
The prevalence of cocaine abuse has increased greatly over the past decades and now represents a major public health problem worldwide. Cocaine is highly addictive
Cocaine is an alkaloid found in the leaves of
E. coca.
It was used as a local anesthetic and to dilate pupils in ophthalmology
Cocaine blocks the uptake of dopamine,
noradrenaline
, and
serotonin.
Given IV or by sniffing: a rapid stimulating effects similar to amphetamine.
It causes toxic psychosis & ulceration of the nasal mucosa& Other serious side effects.
Slide23Slide24Slide25Nicotine:
Nicotine is selective agonist of the nicotinic acetylcholine receptor .
In terms of numbers affected, addiction to nicotine exceeds all other forms of addiction.
Nicotine exposure occurs primarily through smoking of tobacco, which causes associated diseases that are responsible for many preventable deaths. The chronic use of chewing tobacco and snuff tobacco is also addicting.
Smoking-associated diseases
:include lung cancer, heart disease, atherosclerosis, laryngeal cancer, oral cancer,
oesophageal
cancer, COPD, intrauterine growth retardation & low birth weight.
Slide26Tolerance
: very quick perhaps due to desensitization of receptors.
withdrawal
syndrome
: craving
! increased
irritability, anxiety, impaired performance of psychomotor tasks, aggressiveness ,sleep disturbance
s
, headache and increased appetite.
highly addictive
with the very strong psychological component.
Slide27Treatment of nicotine dependence
Most smokers would like to quit but few succeed
Combination of psychological and pharmacological treatment achieve success rate about 25% (after 1 year)
.
Nicotine replacement therapy: Nicotine in patches (controlled release), chewing gums, nasal sprays several times daily (short effect)
Adjunct therapy
:
Bupropion
: an
antideprssant
that
reduces the severity of nicotine cravings and withdrawal symptoms .It
inhibits
the reuptake of dopamine and so increase dopamine activity in nucleus a
c
cumebens
.
Treatment course lasts for seven to twelve weeks
.
Clonidine
– rarely used due to the side-effects (hypotension, drowsiness…)
.
Slide28Cannabis
and Cannabinoids
Extracts of the hemp plant (
Cannabis
sativa,Canabis
indica
)
Cannabis mostly smoked produces a sensation of relaxation & well-being.
Cannabis contains chemicals called
cannabinoids
.One of these, delta-9-tetrahydrocannabinol (THC), is believed to be responsible for most of the characteristic psychoactive effects of cannabis.
Marijuana
: (
dried leaves and flower heads)
is one of the most frequently encountered illicit(illegal) drug worldwide.
Hashish
:
consists of the THC-rich resinous material of the cannabis plant, which is collected, dried, and then compressed into a variety of forms, such as balls, cakes
.
Their
CNS effects
are
combination of
psychotomimetic
& depressant effects
eg
: relaxation, well-being and euphoria ,uncontrolled laughing ,a feeling sharpened sensory awareness, with tastes, sounds and sights more intense and fantastic ,impairment of motor coordination (driving), impaired short-term memory and judgement, increased
appetite ,
analgesic effect
,antiemetic effect.
Slide29Slide30Slide31Mechanism of action
is through
cannabinoid
(CB) receptors
(
CB
1
- brain ) highly abundant in: hippocampus (memory), cerebellum (loss of coordination), and
substantia
nigra
(motor disturbances), hypothalamus (appetite) and
mesoli
m
bic
dopaminergic
pathway (reward) and cortex.
The synthetic
9
-THC analog
dronabinol
is approved
cannabinoid
agonist currently marketed in the USA and some European
countries for the treatment of anorexia in AIDS patients, as well as for refractory nausea and vomiting of patients undergoing chemotherapy.
Nabilone
, an older
9
-THC analog used as an antiemetic and as an adjunct analgesic for neuropathic pain.
Tolerance and physical dependence occur only to a minor degree in heavy users
. Withdrawal
syndrome: weak and usually mild irritability, restlessness, confusion, sweating tremor and sleep disturbances.
Rimonabant
is selective CB1receptor blocker used as an anorectic anti-obesity drug It can opposite effects of
cannabinoids
.
5.Hallucinogens
Hallucinogens are substances produce changes in perception, thought and mood.
Thoughts and perceptions tend to become distorted and dream-like, colours and sounds are more sharp
. Different kind of hallucinations (visual, auditory, tactile and olfactory) appear.
Thought
process tend to be illogical and disconnected
Lysergic acid diethylamide (
LSD
) is the most potent hallucinogen (agonist at 5-HT
2
receptors) .Others include:
Psilocybin,Mescaline
( agonists at 5-HT
2
receptors)
MDMA
(
Methylenedioxymethamphetamine
) (
Ecstasy
)called as "street" or "party" drug. It is an amphetamine derivative which acts mainly by inhibiting 5-HT uptake and has powerful
psychostimulant
effects typical of amphetamines, as well as
psychotomimetic
effects.
Phencyclidine called as “angel dust” and
ketamine
are
antagonists at NMDA(N-methyl-D-aspartic acid)-type glutamate receptors.
Slide33Slide346.Inhalants
Inhalants are a diverse group of substances that include volatile solvents, gases, and nitrites that are inhaled.
These substances are found in common household products like glues, lighter fluid, cleaning fluids, and paint products.
The chronic use of inhalants has been associated with a number of serious health problem:
Sniffing glue and paint thinner causes kidney abnormalities, while sniffing the solvents toluene and trichloroethylene cause liver damage.
Memory impairment, attention deficits, and diminished intelligence
Deaths resulting from heart failure, asphyxiation, or aspiration have occurred.
Slide35Slide367.Anabolic steroids
A type of
steroid that mimics the male sex hormone testosterone.
Medical uses of anabolic steroids include replacement of inadequate levels of testosterone resulting from a reduction or absence of functioning testes,& also for certain kinds of anemia and breast cancer.
Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. But using them this way is not legal or safe.
Anabolic steroids have many psychological and physical side effects Including:
Liver
damage and cancer
Sterility, reduction of the size of the testes and breast enlargement in men.
Increased facial hair ,a deeper voice and decreased breast size in women.
Acne.
Permanently stunted growth in adolescents.
Aggressive behavior, mood swings, depression.
Hypertension.
High cholesterol.
Injuries to tendons and muscles.
Slide37Slide38General Management of drug abuse:
Stopping the use of the substance.
2.Pharmacotherapy
: as use of antidotes
e.g
:
Naloxone
for
opioid
abuse.
or substituting agents
e.g:a
long acting
opioid
(
e.g:methadone
) for shorter acting one(
e.g:heroin
) &use of chewed or
transdermal
nicotine.
3.Long term support, rehabilitation & Psychosocial therapies.