Drug Abuse Drug abuse is - PowerPoint Presentation

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Drug Abuse

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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

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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 .

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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

)

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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.

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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

.

 

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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.

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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.

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opium poppy

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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.

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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.

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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

.

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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.

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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.

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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.

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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).

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3.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.

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Khat

leaves

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Cocaine

:

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.

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Nicotine:

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.

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Tolerance

: 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.

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Treatment 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…)

.

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Cannabis

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.

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Mechanism 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

.

 

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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.

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6.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.

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7.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.

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General 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.