Drug Abuse (1) Drug abuse - PowerPoint Presentation

Slide1

Drug

Abuse (1)

Drug 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

Characteristics 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 .

2.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

)

pharmacokinetic

(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.

Aetiology

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.

Types 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

Treatment

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.

2.

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.

Both 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

.

Alcohol (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.

Tolerance 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.

Alcohol-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.

Treatment 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).