Drugs of abuse

Abdullah Al Omairi
Adil Al Ghafri
Ahmed AlMazroui
Khalid Al Saidi
Outlines
• Definitions.
• Diagnosis of dependence.
• Treatment strategies of drugs of abuse.
• Classification of drugs of abuse.
• In each class:
– Withdrawal symptoms
– Tolerance and dependence
– Overdose
– treatment
• Clinical case ( heroin lung).
Definitions

Intoxication

Withdrawal

Tolerance

Dependence
Intoxication

The psychological and
physical effects of the
substance that disappear
when the substance is
eliminated.
Withdrawal

Symptoms and signs occurring when the
substance is reduced or stopped.

Tend to opposite to the original effects
produced by the drug before tolerance
developed.
Tolerance

The state in which
repeated
repeated
administration leads
administration leads
to decreasing effect
to decreasing effect



Tolerance develops to
some
some drug
effects
effects much
more
more rapidly than to
other effects
other effects of the
same drug
sensitization
tolerance
DOSE
R
E
L
A
T
I
V
E

E
F
F
E
C
T
Shift in a dose-response curve with
tolerance & sensitization
Tolerance

Types of tolerance:

innate
innate (preexisting sensitivity or insensitivity)

Acquired:
Acquired:

pharmacokinetic (dispositional or metabolic)

Pharmacodynamic

Learned tolerance (behavioral, conditioned)

Acute tolerance
Acute tolerance

Reverse tolerance
Reverse tolerance (sensitization)

Cross tolerance
Cross tolerance
Dependence

Repeated
Repeated, periodic, or continuous
administration of a drug that results in harm to
the individual and sometimes to society.
Dependence

Physical:

Adaptation produced by a resetting of homeostatic resetting of homeostatic
mechanisms mechanisms in response to repeated drug use.


Psychological:

Some of the symptoms experienced as a substance is
withdrawn, become conditioned responses that reappear
when withdrawal takes place again.

Cognitive factors: patient expect unpleasant symptoms and
are distressed by the prospect.

Dependence

Dependence syndrome:

Three of the following characteristics occurring at
any time in the
past 12 months
past 12 months:
1. Strong desire (craving)
2. Withdrawal
3. Tolerance
4. Difficulties in stopping using the substance or limiting
the amount taken.
5. Neglect of alternative pleasures or interest.
6. Persistence use despite harm.
Patients who take medicine for appropriate
medical indications and in the correct dose still
may show tolerance, physical dependence, and
withdrawal symptoms if the drug is stopped
abruptly rather than gradually
Principles of treatment
1. Assessment:

The type of drug and amount taken

Evidence of dependence

Consequences of drug taking

caused by the drug

Related to intravenous use

Social & psychological

Motivation
1. Arrange withdrawal
2. Rehabilitation
Principles of treatment

Maintenance programmes

1. To remove the need to obtain street drugs
2. To stop intravenous use
3. To provide social & psychological help
Type Examples
Narcotic analgesics (opioids ( Morphine
Heroin
General CNS depressants Ethanol
solvents
Hypnotics & Anxiolytics Benzodiazepines
barbiturates
Psychomotor stimulants Amphetamines
Cocaine
Caffeine
nicotine
Psychotomimetic agents LSD
cannabis
Anxiolytics & hypnotics

Benzodiazepines


Barbiturates
Benzodiazepines

Pharmacological effects and uses:

Reduction of anxiety and aggression

Sedation and induction of sleep

Reduction of muscle tone & coordination

Anticonvulsant effect

Side effects:

Drowsiness, dizziness, fatigue, psychomotor
impairment & anterograde amnesia
Benzodiazepines

Mechanism of action:

Enhance the response to GABA.

Binding to a site on GABAA receptors, increasing
their affinity for GABA ¬ lead to increased
opening frequency of these ligand gated Cl-
channels, thus Potentiating the effect of GABA
release in terms of inhibitory effects on the post
synaptic cells.
Benzodiazepines

Intoxication:

In general, lone BZD overdoses are remarkably
safe & near full recovery takes place within 24 Hr.

Toxicity is increased by malnutrition, advanced
age, concomitant use of alcohol and other CNS
depressants.

Antidote: flumazenile
Benzodiazepines

Withdrawal syndrome:

Following moderate dose usage:

Anxiety, agitation

Disturbed sleep

Increased perceptual sensitivity

Muscle cramps

dizziness

Tremor, sweating, palpitations

Following high dose usage:

Seizures

delirium
Benzodiazepines

The withdrawal symptoms are less pronounced
with long acting (e.g. diazepam) than with
short acting (e.g. lorazepam).
Barbiturates

Non-selective CNS depressants.

Increase GABA mediated inhibition by acting
on the same receptors as BDZ.

Used in anesthesia (thiopental) and treatment
of epilepsy (phenobarbital).

Use as sedative and hypnotic agents is no
longer recommended.

Induce a high degree of tolerance and
dependence.
Barbiturates

Intoxication:

Mild: resembles alcohol intoxication (slurred speech,
incoherence, drowsiness, depression of mood).

Moderate: greater depression of mental status, response
only to painful stimuli, decreased deep tendon reflexes and
slow respiration.

Severe: coma and loss of all reflexes (except the papillary
light reflex).

Withdrawal syndrome resembling that occurring with
alcohol with a high risk of seizures.
Depressant:
Alcohol, Opioids
ADIL AL-GHAFRI
Alcohol
+
Initial effect, stimulation ¬ suppression of inhibitory
system.
+
Dysphoria!! tension-reduction explanation.
+
One unit is equal to 8g, 10ml of ethanol = ½ pint of normal
strength beer or 1 standard glass of wine.
+
Safe levels: 21units/wk= ♂, 14units/wk=♀.
+
Dangerous levels: 50units/wk=♂, 35untis/wk=♀.
Cont… Alcohol
+
Action:
i. Enhances inhibitory effect of GABA stimulated
chloride channels.
ii. Inhibits the excitatory NMDA (N -methyl-D-
asparatate) receptors.
iii. Potentiate 5-HT3 activated ion channels.
Cont… Alcohol
+
Pharmacological effects:
¤
Acute intoxication on the brain:
I. Early intoxication
(15-30 mg/100ml): *euphoria, *impulsive speech,
*increase self confidence, *reduced insight.
II. Moderate intoxication
(30-100 mg/100ml): *decrease performance,
*motor incoordination, *impaired judgment.
III. Severe intoxication
(>100mg/100ml): *midbrain & cardio respiratory
depression.
Cont… Alcohol
+
Other Acute effects:
-
Peripheral coetaneous vasodilatation (risk of
hypothermia).
-
+ secretion of ADH ¬ ^diuresis.
-
+ secretion of oxygen ¬ delayed labor.
-
^ catecholamine & hydrocortisone plasma levels.
-
^ histamine and gastrin release from gastric mucosa
¬ ulcer.

-
Competition of acetic acid with uric acid for excretion
in kidney ¬ acute gout.
-
Direct cardiac effects e.g. arrhythmias.
Cont… Alcohol
+
Chronic effects:
-
Neurological complications: **peripheral
neuropathy, **dementia, **cerebral atrophy,..
-
Hepatitis, cirrhosis, hepatic failure.
-
Protective effect on coronary heart failure.
Cont… Alcohol
+
Foetal alcohol syndrome: (10%)
Very heavy drinking pregnancy may cause:
-
Facial abnormalities.
-
LBW.
-
Low intelligence.
-
overactivity.
Cont… Alcohol
+ Kinetics:
- 95% of absorbed alcohol
metabolized, the remainder
being excreted in urine,
breath, sweat.
- Metabolized in liver to
acetic acid that enter citric
acid cycle or are utilized in
various anabolic reactions.
Cont… Alcohol
+
Tolerance:
-
Experience with alcohol can produce great
tolerance.
+
Dependence:
-
Physical & psychological dependence developed.
Cont… Alcohol
+
Overdose Rx:
-
If patient's mental status is severely depressed, insert an
endotracheal tube before performing gastric lavage if the
patient present <1 hr after ingestion.
-
Charcoal not helpful due to rapid absorption of ethanol from
stomach.
-
Consider hemodialysis if blood conc. >5g/l or arterial pH<7.
-
Administer 100mg thiamine iv followed by 50 ml 50%
dextrose in water iv to any comatose alcoholic patient.
-
Consider admission if : underlying illness, significant
alcoholic ketoacidosis, or ventilatory support needed.
-
observe till blood alcohol level <100mg/dL
Cont… Alcohol
+
Withdrawal syndrome.(
6hrs)
-
Alcohol craving.
-
Tremor**, irritability.
-
Nausea.
-
Sleep disturbance.
-
Tachycardia.
-
Hypertension.
-
Sweating.
-
Perceptual distortion.
-
Seizures. (12-24hr after last
drink)
-
Delirium tremens
( rare in uncomplicated
withdrawal, 48hr)

severe agitation.

Confusion.

visual hallucination.

fever, profuse
sweating.

tachycardia.

nausea, diarrhea.

dilated pupils.
o
Last 3-4 days
o
Worse at night.
o
End in prolong & deep
sleep.
Cont… Alcohol
-
Withdrawal symptoms usually not severe or life
threatening until they occur in conjunction with
other problems:
*infection.
*trauma.
*malnutrition.
*electrolyte imbalance.
Cont… Alcohol
+
Treatment of Withdrawal Syndrome:
-
Considered as lethal condition. Mild ¬ never come.
-
Severe cases:
Q
Long acting BZD ( chlordaizepoxide, diazepam): drugs of choice
unless liver impairment, not >10 days.
** chlordaizepoxide: orally 10-50mg gradually reduced over 7-
10days.
Q
Short acting BZD e.g. Oxazepam.
Q
anti-convulsant : carbamazapine may have effects.
Q
β- blocker may given to attenuate sympathetic overactivity
symptoms.
Q
If Hx of seizures, use phenytoin.
Q
Hydration & electrolyte balance.
Q
Vitamins, orally high dose thiamine.
Q
Monitor symptoms, BP, fluid intake.
Q
Advice on consumption of juices & soft drink.
Cont… Alcohol
+
Acamprosate:
Q
maintenance.
Q
Appear to reduce the effect of excitatory amino acids such
glutamate, & modifies GABA neurotransmission .
Q
Increase # of alcohol free days & the chance of subsequent
complete abstinence.
Q
Benefit may last for 1 yr after stopping it.
Q
GI Side effects.
Cont… Alcohol
+
Benzodiazepine antagonist, Flumazenil «
can reverse the acute central depressant effect
of ethanol.
+
Disulfiram
-
Inhibit ethanol metabolism ¬ acetaldehyde
accumulation gives toxic symptoms like: *headache
*nausea, *flush, *tachycardia, *hyperventilation.
-
200-400mg/daily.
+
Also Naltrexone, (opiate receptor antagonist),
appear to block some of the reinforcing properties of
alcohol.
Opioids
+
Opiate: is a drug derived from alkaloids of the
opium poppy. (شاخشخلا تابن)
+
Used primarily as analgesics.
+
Misused to obtain effects on mood.
Cot...Opioids
+
Opioids include:
I. Morphine analogues:
compound closely related
to morphine .e.g.

-
morphine.
-
diamorphine. ( heroin)
-
3-methoxymorphine.
(codeine)
II. Synthetic derivatives:
compound with structures
unrelated to morphines.
e.g.
-
pethidine.
( mepyridine,USA)
-
fentanyl.
-
methadone.
Cot...Opioids
+
Receptors:
1. µ (mu) receptors: analgesic effects (through NMDA,
N-methyl-D-asparatate), unwanted effects: *respiratory
depression, *euphoria, *sedation, *dependence)
2. δ (Delta) receptors: important peripherally, may
contribute to *analgesia.
3. κ (Kappa) receptors: contribute to *analgesia at
spinal level, may cause *dysphoria & *sedation, no
contribution to dependence.
Cot...Opioids
µ δ κ
Analgesia
-Supraspinal
-Spinal
-peripheral
+++
++
++
-
++
-
-
+
++
Respiratory depression +++ ++ -
Pupil constriction ++ - +
+GI motility ++ ++ +
Euphoria +++ - -
Dysphoria - - +++
Sedation ++ - ++
Dependence ** +++ - +
Cot...Opioids
+
Route of abuse: i.v, smoked (inhalation) or
nasally (snorted).
+
Duration of action: 3-4hr.

+
Tolerance: developed rapidly.
+
Dependence: physical dependence develop
rapidly & characterize by a definite abstinence
syndrome following withdrawal.
Cot...Opioids
+
Kinetic:
Q
Absorption of morphine from GIT slow,
it undergoes extensive 1
st
pass metabolism.
***I.V. : 100% availability.
Q
Opioids cross placental barrier & may depress
respiration in fetus.
***Pethidine does not cross placental barrier.
Q
Small % of morphine cross BBB in contrast to more
lipid-soluble drugs.( fentanyl, heroin) which enter
brain readily.

Cot...Opioids
Q
Morphine metabolized in the liver to
glucuronides,metabolite excreted mainly in the
urine & little in the bile.
Cot...Opioids
Withdrawal
syndrome:
(starts 8-10hrs after last
dose, not life threatening)
+
Symptoms:
Q
Craving for opioids.
Q
Restlessness, irritability.
Q
Increase sensitivity to pain.
Q
Nausea, cramp.
Q
Muscle aches
Q
Dysphoric mood
Q
Insomnia, anxiety.
+
Signs:
Q
Pupillary dilatation.
Q
Sweating.
Q
Piloerection.
Q
Vomiting, diarrhea.
Q
Yawning.
Q
Fever.
Q
Tachycardia, ^BP (late
stage)
Cot...Opioids
Q
Rx:
+
Detoxification: 3 methods:
1. Long acting opioid: methadone.
*20-30mg as initial dose, tapered 20% / day during the course of detoxification.
2. Centrally acting sympatholytic agent, Clonidine
-
α-2 adrenergic agonist.
-
Reduce central sympathetic outflow.
-
Mimic opioid effects alleviating many of withdrawal symptoms:
autonomic symptoms.
-
E No narcotic action, not addictive.
-
E Does not alleviate generalized ache & craving.
×
Lofexidine, clonidine analog, with less hypotensive effect.
Cot...Opioids
3. Involve activation of endogenous opioid
system without medication.
-
The technique proposed include acupuncture &
several methods of CNS activation utilizing
transcutaneous electrical stimulation.
-
Theoretically attractive, not found to be practical.
Cot...Opioids
+
Maintenance:
Q
Orally daily dose of long acting opioid agonist,
methadone.
-
Methadone saturates the opioid receptors &
prevent the desired sudden onset of CNS effects
normally produced by i.v administration.
Q
Buprenorphine:
-
partial opioid agonist, can be given once daily or
even less/ sublingually/ of dose 2-20mgdaily.
Cot...Opioids
high
normal
sick
heroin
methadone
Time (hrs(
Cot...Opioids
Q
Narcotic antagonist:
×
Naltrexone: long acting orally active pure opioid
antagonist.
×
High affinity to µ -opioid receptor.
×
Not satisfying craving or relieving protracted
withdrawal symptoms.
×
utilized after detoxification for patients with high
motivation to remain opioid-free.
×
No dependence.
Cot...Opioids
+
Overdose:
×
respiratory depression.
×
coma.
×
meiosis.
×
behavioral restlessness.
×
Hyperactivity.
×
dysphoria.
×
postural hypotension.
×
urinary retention.
×
itching around nose.
Cot...Opioids
+
Overdose Rx

-
Provide respiratory support. ( O2 monitoring. ABG)
-
Naltrexone: reverse toxicity, used as bolus dose ( 0.8-2
mg i.v. in adult).
-
Repeated every 2 minutes as necessary until level of
consciousness and respiratory rate increase & pupils
dilate.
-
Diagnostic test! Failure to respond to it indicate a cause
other than morphine.
-
Treat coma & hypotension.
-
Non-carcinogenic pulmonary Oedema, in severe cases
does not usually respond to diuretic therapy, CPAP
and/or PEEP (positive end-expiratory pressure) may required.
Stimulants Stimulants
1 - Amphetamine .
2 - Cocaine
3 - Caffeine .
4 - Nicotine
Referred to as “uppers , ”
-
reverse the effects of fatigue on both mental and physical
tasks.
-
temporarily increase alertness and awareness.
1 - Amphetamine
Dextroamphetamine
Methylamphetamine
( speed (
Cathinone (Khat (
Methylenedioxymethamphetamine
( Ecstasy (
1 - Amphetamine
Mechanism of Action
-Release of Catecholamines ( Dopamine, Noradrenaline and Serotinine) in the brain.
-Decrease MAO Destruction.
-Release of Noradrenaline from sympathetic nerves.
Route of Abuse
I.V ( Amphetamine sulphate (.
Orally (P.O), Nasal Route .
Smoked (e.g Methamphetamine (.
Amphetamine
Pharmacological Effects
On CNS :
Excess Dopamine action :
+
Locomotor Stimulation.
+
Euphoria.
+
Excitement.
+
Anorexia.
+
Stereotyped behaviour.
+
Insomnia.
+
Amphetamine Psychosis.
On Sympathetic nervous system :
Excess Noradrenaline Action on blood vessels and Heart: Tachycardia .
Vasoconstriction .
Increased BP .
Arrhythmias .
Amphetamine
Tolerance and Dependence
Q
Tolerance develop rapidly to peripheral sympathomimetic and anorectic effects.
Q
Dependence : due to
-
Unpleasant After-effects.
-
Strong Desire for euphoric state.

Chiefly Psychological dependence.
Q
Withdrawal Syndrome :
-
Lethargy and Low energy.
-
Deep sleep.
-
Depression.
-
Dysphoria.
-
Hungry.

Amphetamine
Pharmakinetics
Q
Absorbed from GIT and Freely penetrates Blood-brain barrier( BBB).
Q
Absorbed from the nasal mucosa.
Q
Plasma Half life is between 5-20 H.
Q
Elimination :
Excreted unchanged in the urine depending on the flow of urine and
urine PH ( more in an acidic urine ).
Amphetamine
Therapeutic uses
×
Attention Deficit/Hyperactivity Disorder ( ADHD) : Methylphenidate or Dexamphetamine.
×
Narcolepsy.
×
Appetite Suppressant in Obesity ( Fenfluramine).
Acute Poisoning : arrhythmias , MI, Coronary and Cerebral thrombosis .
Chronic overdose : Psychotic state, Vasculitis of cerebral and/or renal vessels .
Amphetamine
Treatment of Overdose
Sedation ( Diazepam ) and Management of any
Hyperpyrexia or Cardiac arrhythmias .
Amphetamine Psychosis : Haloperidol (antipsychotic (.

Depression : Antidepressants .

Cathinone :
Leaves and stems of Khat plant .
Street names : kat, qat, chat, gat, tohai, tschat and mirraa .
Route of abuse : Chewed .
2 - Cocaine

Cocaine free base
( Crack (
Cocaine
( Hydrochloride salt (
Alkaloid from the Coca
Plant .
Mechanism of Action
×
Blockade of Norepinephrine, Serotonine and Dopamine re-uptake into the presynaptic
terminals .
×
Pontentiate and prolong the CNS and Peripheral actions of these Catecholamines.
Route of Abuse
Nasal route , Smoked (crack), IV, Sniffing .
Cocaine
Cocaine
Pharmacological Effects
Similar to Amphetamine but more potent : ( Super Amphetamine (.

o On CNS :
º
locomotor Stimulation.
º
increase in self-confidence , performance and sense of well-being.
º
Euphoria ( Limbic system ).
º
Stereotyped behaviour, Psychosis and Paronia. ( Repeated doses)
o On Peripheral Nervous System:
º
Tachycardia.
º
Vasoconstriction.
º
High Blood Pressure.
º
Sweating.
º
Arrhythmias.
o Local Anaesthetic Properties ( Eye Surgery).

Cocaine
Tolerance and Dependence .
+
Tolerance Develops rapidly.
+
Dependence:
same as Amphetamine : mainly Psychological Dependence .
+
Withdrawal Symptoms ( Crash) : same as Amphetamine:
-
Dysphoria.
-
Irritability.
-
Hypersomnia.
-
Depression.
Cocaine
Acute Overdose: Cardiac dysrhythmias, Convulsions., Respiratory Depression, coronary
and Cerebral thrombosis ,premature labor, Foetal malformation .
Treatment
Sedation ( Diazepam (.
Psychosis or Depression ( Antipsychotic or antidepressant (.
Propranolol or Calcium Channel-blocker .
3 - Caffeine
Caffeine
Mechanism of Action
Blocking Adenosine Receptors (antagonist (.
At High Concentration : Inhibits phosphodiesterase¬ Intracellular cAMP .
Stimulate cellular Calcium influx .
Caffeine
Pharmacological effects
+
Bronchial Relaxation( adenosine receptors).
+
Ordinary Consumption of Coffee: release Catcholamines :
-
Increase BP( Peripheral vasoconstriction).
-
Positive Inotropic and Chronotropic effects.
+
Psychotomotor Stimulant ( 3 cups of coffee = 200mg caffeine):
-
Reduced Fatigue.
-
Insomnia.
-
Improved Concentration.

Caffeine
+
Increases Diuresis. ( Reduced tubular reabsorption of Na ,, weak Thiazide Action,,).
+
Increases Gastric secretion. (peptic ulcer).
Cont .
Q
Well Absorbed orally.
Q
Can cross the placenta.
Q
Half Life ( 2-12 H).
Q
Metabolized in the liver and excreted through urine.
Pharmacokinetics
Caffeine
Tolerance and Dependence
+
Slight Tolerance to the effects of caffeine ( on all systems) occurs.
+
Dependence :
×
Psychological and Physical.
×
Withdrawal Symptoms ( 5 or more Cups) :
-
Lethargy.
-
Irritability.
-
Headace.


Caffeine
In combination with Ergotamine or aspirin ( for Migraine (.
Therapeutic use
But !!!!! :
Excessive Prolonged Consumption :
-
Anxiety.
-
Restlessness.
-
Tremors.
-
Insomnia.
-
Cardiac Extrasystoles.
Nicotine
Is
A Killer
( Pipe , Cigarette, Cigar (
Cigar
Pipe
Cigarette
Nicotine
Mechanism of Action
++ Nicotinic Ach Receptors in autonomic ganglia and adrenal gland :
release of Catcholamines ,Serotonin, ADH :
-
Tachycardia.
-
Increase Cardiac Output.
-
Increase BP.
-
Increase Gastrointestinal motility.
-
Sweating.

Nicotine
++ Nicotinic Ach Receptors in brain :
-
Arousal ( small doses).
-
Pleasant feeling.
-
Decreased appetite.
-
Convulsions and coma (a high doses).
++ ADH ¬ decrease Diuresis.
Cont .
Pharmacokinetics
Q
An average cigarette contains 0.8 g of Tobacco and 9-17 mg of
Nicotine of which 10% is absorbed.
Q
Half life is 2 H.
Q
Elimination : in urine depending on pH.
Nicotine
Tolerance ad Dependence
+
Tolerance develops rapidly.

+
Dependence :
Q
Psychological and Physical.
Q
Withdrawal Symptoms ( lasts for weeks):
-
Irritability.
-
Impaired Psychomotor performance.
-
Sleep Disturbance.
-
Increase Appetite.


Nicotine
Long-Terms Risks
Q
Cancer: Bronchogenic cancer and cancer of mouth and Throat.
Q
Coronary Heart disease.
Q
Chronic Obstructive Lung Disease.
Q
Dangerous effects in pregnancy: risk of :
×
Abortion.
×
Stillbirth.
×
Neonatal Death.
Nicotine
Treatment
Nicotine Replacement Therapy :
Nicotine resin contained in Chewing gum (Nicorette (.
Nicotine Transdermal patches .
Clonidine (α2 adrenoceptor agonist ( :
Reduce withdrawal effects .
Oman and Tobacco .
Unsmoked Tobacco.
E.g.: Afdhal((ةغضم,لضفأ
Pan parag, guthka(هاكتوج ,كاربناب)
tambac((كابمت
Others: pan(ناب) ,bangi( (يجناب
Tambacu((وكابمت, Alnshooq( (قوشنلا
Alshma((ةمشلا
ALsubari ((يرابوسلا
Afdhal( Afdhal(( (ةغضم,لضفأ ةغضم,لضفأ
Rout of abuse Rout of abuse : :
- - Between the lips and gingiva, or between cheek and gingiva Between the lips and gingiva, or between cheek and gingiva . .
Tombac(
Tombac(
(
(
كابمت
كابمت

Tobacco, Betel nut, Lime
Tobacco, Betel nut, Lime
Pan parag, guthka
Pan parag, guthka
(
(
,كاربناب
,كاربناب
هاكتوج
هاكتوج
)
)
Shisha
One head of Muasel = 20 regular cigarettes .
A Smoker is not affected by Normal Aging .
Because he dies younger .
A smoker always adds a person to his friends list .
Because he visits a new doctor everyday .
Thieves don’t steal his house .
Because he keeps coughing the whole Night .
A smoker is not visited by his relatives or other people .
Because of his bad smell .
Khalid Al-Saidi
Khalid Al-Saidi
The outline
The outline
Þ
Hallucinogens: LSD
Hallucinogens: LSD
Þ
Cannabis
Cannabis
Þ
Inhalants
Inhalants
Þ
Date rape drugs
Date rape drugs
Þ
Conclusion
Conclusion
Þ
Clinical case
Clinical case
LSD
LSD
Þ
LSD: lysergic acid diethylamide.
LSD: lysergic acid diethylamide.
Þ
Action:
Action:
agonist effect at presynaptic 5-
agonist effect at presynaptic 5-
HT receptors in the CNS.
HT receptors in the CNS.
Þ
Route of abuse:
Route of abuse:
usually p.o.
usually p.o.
Þ
Duration of action:
Duration of action:
effect start after
effect start after
40-60 min & lasting for 6-8 hrs.
40-60 min & lasting for 6-8 hrs.
LSD
LSD
Pharmacological effects:
Pharmacological effects:
Þ
Produces perceptual distortions & sometimes
Produces perceptual distortions & sometimes
hallucinations.
hallucinations.
Þ
Mood changes including elation, paranoia,
Mood changes including elation, paranoia,
depression, intense arousal, & sometimes a
depression, intense arousal, & sometimes a
feeling of panic.
feeling of panic.
Þ
Pupillary dilation, increased BP & pulse,
Pupillary dilation, increased BP & pulse,
flushing, salivation, lacrimation &
flushing, salivation, lacrimation &
hyperreflexia.
hyperreflexia.
LSD
LSD
Þ
Tolerance does develop to the
Tolerance does develop to the
behavioural effects but no withdrawal
behavioural effects but no withdrawal
syndrome has been observed.
syndrome has been observed.
Þ
Diazepam may be given to control
Diazepam may be given to control
severely agitated drug abuser.
severely agitated drug abuser.
Phencyclidine
Phencyclidine
Þ
PCP or ‘angel dust’ is a synthetic hallucinogen with
PCP or ‘angel dust’ is a synthetic hallucinogen with
dangerous effects.
dangerous effects.
Þ
Intoxication an be prolonged & hazardous with
Intoxication an be prolonged & hazardous with
agitation, aggressive behavior & hallucination
agitation, aggressive behavior & hallucination
together with nystagmus & raised BP.
together with nystagmus & raised BP.
Þ
With high doses: ataxia, muscle rigidity, convulsions &
With high doses: ataxia, muscle rigidity, convulsions &
an adrenergic crises.
an adrenergic crises.
Þ
Haloperidol or diazepam may be given for treatment.
Haloperidol or diazepam may be given for treatment.
Cannabis
Cannabis
Þ
Obtained from the plant
Obtained from the plant
Cannabis
Cannabis
sativa
sativa
.
.
Þ
Two forms:
Two forms:
The preparation that are smoked are called
The preparation that are smoked are called
marijuana
marijuana
& consist of crushed leaves &
& consist of crushed leaves &
flowers.
flowers.
The resin scrapped off the plant is known
The resin scrapped off the plant is known
as
as
hashish
hashish
.
.
Cannabis
Cannabis
Mechanism of action:
Mechanism of action:
Þ
Active compound:
Active compound:
tetrahydrocannabinoil
tetrahydrocannabinoil

(THC).
(THC).
Þ
Receptors:
Receptors:
CB1-receptor: central & peripheral neurons.
CB1-receptor: central & peripheral neurons.
CB2-receptor: immune cells.
CB2-receptor: immune cells.
Cannabis
Cannabis
Pharmacological effects:
Pharmacological effects:
Þ
They commence within minutes of starting to smoke &
They commence within minutes of starting to smoke &
last 2-3 h.
last 2-3 h.
Þ
Euphoria is common.
Euphoria is common.
Þ
Sensations become more vivid.
Sensations become more vivid.
Þ
It distorts experiences of time & space.
It distorts experiences of time & space.
Þ
Recent memory & attention impaired.
Recent memory & attention impaired.
Þ
Cognitive function impaired.
Cognitive function impaired.
Þ
The physical signs include reddening of the
The physical signs include reddening of the
conjunctiva, dry mouth & tachycardia.
conjunctiva, dry mouth & tachycardia.
Cannabis
Cannabis
Þ
Tolerance develops rapidly, but it also
Tolerance develops rapidly, but it also
disappears rapidly.
disappears rapidly.
Þ
Psychological dependence can develop
Psychological dependence can develop
but physical dependence does not occur.
but physical dependence does not occur.
Cannabis
Cannabis
Þ


A motivational syndrome’
A motivational syndrome’
Þ
Cannabinoids & skilled tasks
Cannabinoids & skilled tasks
Cannabis
Cannabis
Clinical use:
Clinical use:
Þ
As antiemetic in cancer patient.
As antiemetic in cancer patient.
Þ
Chronic pain & migraine.
Chronic pain & migraine.
Þ
Muscle spastisity in multiple sclerosis.
Muscle spastisity in multiple sclerosis.
Inhalants
Inhalants
Þ
Industrial solvents, including a variety
Industrial solvents, including a variety
of hydrocarbon, such as toluene.
of hydrocarbon, such as toluene.
Þ
Aerosol propellants, such as
Aerosol propellants, such as
fluorocarbons.
fluorocarbons.
Þ
Organic nitrates, such as amyl or butyl
Organic nitrates, such as amyl or butyl
nitrate.
nitrate.
Inhalants
Inhalants
Acute intoxication
Acute intoxication
Þ
Slurring of speech
Slurring of speech
Þ
Disorientation
Disorientation
Þ
Uncoordination of
Uncoordination of
gait
gait
Þ
Nausea & vomiting
Nausea & vomiting
Þ
Coma
Coma
Þ
Visual hallucinations
Visual hallucinations
Complications
Complications
Þ
Liver & kidney damage
Liver & kidney damage
Þ
Peripheral neuropathy
Peripheral neuropathy
Þ
Perceptual disturbances
Perceptual disturbances
Tolerance &
Tolerance &
Psychological
Psychological
dependence
dependence
Date rape drugs
Date rape drugs
Þ
Sometimes used to assist a sexual
Sometimes used to assist a sexual
assault.
assault.
Þ
Examples:
Examples:
GHB (gamma hydroxybutyric acid)
GHB (gamma hydroxybutyric acid)
Rohypnol (flunitrazepam)
Rohypnol (flunitrazepam)
Ketamine (ketamine hydrochloride)
Ketamine (ketamine hydrochloride)
Rohypnol
Rohypnol
Þ
The predominant clinical manifestations
The predominant clinical manifestations
are drowsiness, impaired motor skills &
are drowsiness, impaired motor skills &
anterograde amnesia.
anterograde amnesia.
Þ
It is tasteless, colorless & odorless &
It is tasteless, colorless & odorless &
can be crushed & added to any drink,
can be crushed & added to any drink,
including water, without detection.
including water, without detection.
Conclusion
Conclusion
Þ
Drug abuse is a serious health problem.
Drug abuse is a serious health problem.
Þ
It can cause long term health hazards.
It can cause long term health hazards.
Þ
It can result in death due to overdose or
It can result in death due to overdose or
withdrawal syndrome.
withdrawal syndrome.
Þ
It can lead to Deterioration in social life &
It can lead to Deterioration in social life &
occupational performance.
occupational performance.
Þ
Drugs should be prescribed only if necessary
Drugs should be prescribed only if necessary
& with caution.
& with caution.
Þ
Legalizations provide no guarantee for safety.
Legalizations provide no guarantee for safety.
Clinical case
Clinical case
Þ
M.C. was hospitalized because of
M.C. was hospitalized because of
breathing difficulties
breathing difficulties
. At admission into
. At admission into
hospital he said that
hospital he said that
2h
2h
following his
following his
last dose of
last dose of
heroin
heroin
he usually gets these
he usually gets these
breathing difficulties & he asked for
breathing difficulties & he asked for
help from his GP who recommended that
help from his GP who recommended that
he should be hospitalized. M.C.
he should be hospitalized. M.C.
did not
did not
vomit & did not have diarrhea
vomit & did not have diarrhea
. He was
. He was
hospitalized after further 2h.
hospitalized after further 2h.
Clinical case
Clinical case
What are the causes of his respiratory
What are the causes of his respiratory
difficulties?
difficulties?
Þ
Acute intoxication (overdose):
Acute intoxication (overdose):
Unexpected purity of street drug
Unexpected purity of street drug
Reduced tolerance
Reduced tolerance
Suicide attempts
Suicide attempts
Þ
Lung edema:
Lung edema:
hypersensitivity, product impurity or
hypersensitivity, product impurity or
pulmonary embolism
pulmonary embolism
Þ
Other complications:
Other complications:
septic embolism
septic embolism

Clinical case
Clinical case
Personal history:
Personal history:
M.C. is a
M.C. is a
42
42
yrs old man dependent on heroin.
yrs old man dependent on heroin.
Originally he had used
Originally he had used
heroin intravenously
heroin intravenously
.
.
Because of
Because of
fear of AIDS
fear of AIDS
he changed to the
he changed to the
intranasal method (i.e. by snuffing). At various
intranasal method (i.e. by snuffing). At various
times
times
he had experimented with other kinds
he had experimented with other kinds
of psychotropic agents
of psychotropic agents
: alcohol, cannabis,
: alcohol, cannabis,
various medications (benzodiazepine, cocaine,
various medications (benzodiazepine, cocaine,
amphetamine) but he always returned to
amphetamine) but he always returned to
heroin.
heroin.
Clinical case
Clinical case
Personal history:
Personal history:
He refused treatment by psycho-analysis
He refused treatment by psycho-analysis
or psychotherapy as he believes these
or psychotherapy as he believes these
“fundamentally wrong”. He
“fundamentally wrong”. He
barely copes
barely copes
with his occupation
with his occupation
in information
in information
science. He is
science. He is
still living with his
still living with his
parents
parents
.
.
Clinical case
Clinical case
Examination:
Examination:
Þ
Polypnoea, cyanosis, bilateral miosis.
Polypnoea, cyanosis, bilateral miosis.
Þ
Body temperature 36.6 Cº.
Body temperature 36.6 Cº.
Þ
Crepitations over both lung bases.
Crepitations over both lung bases.
Þ
The heart appeared to be without any
The heart appeared to be without any
pathological findings.
pathological findings.
Þ
The skin is lightly cyanotic, dry, with usual
The skin is lightly cyanotic, dry, with usual
appearance without signs of dehydration.
appearance without signs of dehydration.
Clinical case
Clinical case
Laboratory examination:
Laboratory examination:
Þ
pO2 = 8.6 kPa (65 mm Hg)
pO2 = 8.6 kPa (65 mm Hg)
Þ
pCO2 = 4 kPa (30 mm Hg)
pCO2 = 4 kPa (30 mm Hg)
Clinical case
Clinical case
Þ
Further examination & treatment were
Further examination & treatment were
carried out. Lung X-ray examination:
carried out. Lung X-ray examination:
lung oedema
lung oedema
of non-cardiogenic origin
of non-cardiogenic origin
(caused by opiates).
(caused by opiates).
Naloxone
Naloxone
was
was
administered to the patient but it has
administered to the patient but it has
no effect on his breathing difficulties.
no effect on his breathing difficulties.
Clinical case
Clinical case
Þ
The patient’s treatment is now
The patient’s treatment is now
proceeding: the patient is given
proceeding: the patient is given
oxygen
oxygen
(6L/min) by inhalation. After 5h the
(6L/min) by inhalation. After 5h the
breathing difficulties decreased , the
breathing difficulties decreased , the
cyanosis decreased & monitored values
cyanosis decreased & monitored values
of the blood gases slowly returned to
of the blood gases slowly returned to
the normal values. Changes of lung X-ray
the normal values. Changes of lung X-ray
examination lasted longer than 24h.
examination lasted longer than 24h.
References
References
Þ
Bertram G. Katzung. Basics & clinical
Bertram G. Katzung. Basics & clinical
pharmacology. 8
pharmacology. 8
th th
ed.
ed.
Þ
P. N. Bennett, M. J. Brown. Clinical
P. N. Bennett, M. J. Brown. Clinical
pharmacology. 9
pharmacology. 9
th th
ed.
ed.
Þ
H. P. Rang, M. M. Dale, J. M. Ritter, P. K.
H. P. Rang, M. M. Dale, J. M. Ritter, P. K.
Moore. Pharmacology. 5
Moore. Pharmacology. 5
th th
ed.
ed.
Þ
http://www.emedicine.com
http://www.emedicine.com
Þ
http://en.wikipedia.org
http://en.wikipedia.org
Þ
HeroinAbuse.Net
HeroinAbuse.Net
Abu Musaab
Abu Al-Yaman
Abu Nawwaf
Abu Al-Waleed
Abdullah Al-Omairi
Adil Al-Ghafri
Ahmed Al-Mazroui
Khalid Al-Saidi
Presented by
ةظوفحم قوقحلا عيمج © 2007
تايحت عم ) GROUP A (
Supervisors
Dr. Aly Abdelrahman
Dr. Ragini Vaishnav
Next week
Management of
Acute Poisoning
Drugs of Abuse
Drugs of Abuse
The End
The End

Outlines
• • • • • Definitions. Diagnosis of dependence. Treatment strategies of drugs of abuse. Classification of drugs of abuse. In each class:
– – – – Withdrawal symptoms Tolerance and dependence Overdose treatment

• Clinical case ( heroin lung).

Definitions
• • • • Intoxication Withdrawal Tolerance Dependence

.Intoxication • The psychological and physical effects of the substance that disappear when the substance is eliminated.

.Withdrawal • Symptoms and signs occurring when the substance is reduced or stopped. • Tend to opposite to the original effects produced by the drug before tolerance developed.

Tolerance • The state in which repeated administration leads to decreasing effect… • Tolerance develops to some drug effects much more rapidly than to other effects of the same drug RELATIVE EFFECT sensitization tolerance DOSE Shift in a dose-response curve with tolerance & sensitization .

conditioned) – Acute tolerance – Reverse tolerance (sensitization) – Cross tolerance .Tolerance • Types of tolerance: – – innate (preexisting sensitivity or insensitivity) Acquired: • pharmacokinetic (dispositional or metabolic) • Pharmacodynamic • Learned tolerance (behavioral.

Dependence • Repeated. . periodic. or continuous Repeated administration of a drug that results in harm to the individual and sometimes to society.

. • Psychological: – Some of the symptoms experienced as a substance is withdrawn. become conditioned responses that reappear when withdrawal takes place again.Dependence • Physical: – Adaptation produced by a resetting of homeostatic mechanisms in response to repeated drug use. – Cognitive factors: patient expect unpleasant symptoms and are distressed by the prospect.

Strong desire (craving) Withdrawal Tolerance Difficulties in stopping using the substance or limiting the amount taken. 4. . 3. Neglect of alternative pleasures or interest. 6. Persistence use despite harm. 5. 2.Dependence • • Dependence syndrome: Three of the following characteristics occurring at any time in the past 12 months: months 1.

physical dependence. and withdrawal symptoms if the drug is stopped abruptly rather than gradually .Patients who take medicine for appropriate medical indications and in the correct dose still may show tolerance.

Arrange withdrawal 2. Assessment: – – – The type of drug and amount taken Evidence of dependence Consequences of drug taking • • • caused by the drug Related to intravenous use Social & psychological – Motivation 1. Rehabilitation .Principles of treatment 1.

To remove the need to obtain street drugs 2.Principles of treatment • Maintenance programmes 1. To provide social & psychological help . To stop intravenous use 3.

Type (Narcotic analgesics (opioids General CNS depressants Hypnotics & Anxiolytics Psychomotor stimulants Examples Morphine Heroin Ethanol solvents Benzodiazepines barbiturates Amphetamines Cocaine Caffeine nicotine LSD cannabis Psychotomimetic agents .

Anxiolytics & hypnotics • Benzodiazepines • Barbiturates .

.

psychomotor impairment & anterograde amnesia . dizziness.Benzodiazepines • Pharmacological effects and uses: – – – – Reduction of anxiety and aggression Sedation and induction of sleep Reduction of muscle tone & coordination Anticonvulsant effect • Side effects: – Drowsiness. fatigue.

.Benzodiazepines • Mechanism of action: – Enhance the response to GABA. thus Potentiating the effect of GABA release in terms of inhibitory effects on the post synaptic cells. increasing their affinity for GABA  lead to increased opening frequency of these ligand gated Clchannels. – Binding to a site on GABAA receptors.

lone BZD overdoses are remarkably safe & near full recovery takes place within 24 Hr. – Toxicity is increased by malnutrition.Benzodiazepines • Intoxication: – In general. – Antidote: flumazenile . advanced age. concomitant use of alcohol and other CNS depressants.

sweating.Benzodiazepines • Withdrawal syndrome: – Following moderate dose usage: • • • • • • Anxiety. agitation Disturbed sleep Increased perceptual sensitivity Muscle cramps dizziness Tremor. palpitations – Following high dose usage: • Seizures • delirium .

.g.Benzodiazepines • The withdrawal symptoms are less pronounced with long acting (e. lorazepam). diazepam) than with short acting (e.g.

Barbiturates
• Non-selective CNS depressants. • Increase GABA mediated inhibition by acting on the same receptors as BDZ. • Used in anesthesia (thiopental) and treatment of epilepsy (phenobarbital). • Use as sedative and hypnotic agents is no longer recommended. • Induce a high degree of tolerance and dependence.

Barbiturates
• Intoxication:
– Mild: resembles alcohol intoxication (slurred speech, incoherence, drowsiness, depression of mood). – Moderate: greater depression of mental status, response only to painful stimuli, decreased deep tendon reflexes and slow respiration. – Severe: coma and loss of all reflexes (except the papillary light reflex).

• Withdrawal syndrome resembling that occurring with alcohol with a high risk of seizures.

Depressant: Alcohol, Opioids

ADIL AL-GHAFRI

Dangerous levels: 50units/wk=♂. 14units/wk=♀. One unit is equal to 8g. Safe levels: 21units/wk= ♂. 10ml of ethanol = ½ pint of normal strength beer or 1 standard glass of wine. . 35untis/wk=♀. stimulation  suppression of inhibitory system. Dysphoria!! tension-reduction explanation.Alcohol      Initial effect.

 i. iii. ii. . Potentiate 5-HT3 activated ion channels. Inhibits the excitatory NMDA (N -methyl-Dasparatate) receptors.Cont… Alcohol Action: Enhances inhibitory effect of GABA stimulated chloride channels.

. *impulsive speech. *reduced insight. *motor incoordination. *impaired judgment. *increase self confidence. Severe intoxication (>100mg/100ml): *midbrain & cardio respiratory depression.Cont… Alcohol Pharmacological effects: Acute intoxication on the brain: Early intoxication (15-30 mg/100ml): *euphoria. III. Moderate intoxication (30-100 mg/100ml): *decrease performance. II.   I.

 secretion of oxygen  delayed labor.  Direct cardiac effects e.  catecholamine & hydrocortisone plasma levels.  histamine and gastrin release from gastric mucosa  ulcer. arrhythmias.  .       Competition of acetic acid with uric acid for excretion in kidney  acute gout.g.Cont… Alcohol Other Acute effects: Peripheral coetaneous vasodilatation (risk of hypothermia).  secretion of ADH  diuresis.

Hepatitis.Cont… Alcohol Chronic effects: Neurological complications: **peripheral neuropathy. **cerebral atrophy. hepatic failure. cirrhosis... Protective effect on coronary heart failure. **dementia.     .

Cont… Alcohol Foetal alcohol syndrome: Facial abnormalities.  (10%) Very heavy drinking pregnancy may cause:     . overactivity. LBW. Low intelligence.

Cont… Alcohol Kinetics: 95% of absorbed alcohol metabolized.    . breath. sweat. the remainder being excreted in urine. Metabolized in liver to acetic acid that enter citric acid cycle or are utilized in various anabolic reactions.

    Dependence: Physical & psychological dependence developed. .Cont… Alcohol Tolerance: Experience with alcohol can produce great tolerance.

Charcoal not helpful due to rapid absorption of ethanol from stomach. observe till blood alcohol level <100mg/dL  Overdose       . or ventilatory support needed. >5g/l or arterial pH<7. Consider hemodialysis if blood conc.Cont… Alcohol Rx: If patient's mental status is severely depressed. insert an endotracheal tube before performing gastric lavage if the patient present <1 hr after ingestion. Consider admission if : underlying illness. significant alcoholic ketoacidosis. Administer 100mg thiamine iv followed by 50 ml 50% dextrose in water iv to any comatose alcoholic patient.

• tachycardia. Tachycardia. Tremor**. (12-24hr after last drink) withdrawal.           . Nausea. Seizures. • visual hallucination. • Confusion. 48hr) • severe agitation. • fever. o Last 3-4 days o Worse at night. Perceptual distortion. Sleep disturbance. irritability. • dilated pupils. Hypertension. • nausea. Sweating. diarrhea.(  Delirium tremens ( rare in uncomplicated 6hrs) Alcohol craving. profuse sweating. o End in prolong & deep sleep.Cont… Alcohol Withdrawal syndrome.

*malnutrition. *electrolyte imbalance.Cont… Alcohol Withdrawal symptoms usually not severe or life threatening until they occur in conjunction with other problems: *infection.  . *trauma.

Cont…

Alcohol
Treatment of Withdrawal Syndrome:
Considered as lethal condition. Mild  never come. Severe cases: Long acting BZD ( chlordaizepoxide, diazepam): drugs of choice unless liver impairment, not >10 days. ** chlordaizepoxide: orally 10-50mg gradually reduced over 710days. Short acting BZD e.g. Oxazepam. anti-convulsant : carbamazapine may have effects. β- blocker may given to attenuate sympathetic overactivity symptoms. If Hx of seizures, use phenytoin. Hydration & electrolyte balance. Vitamins, orally high dose thiamine. Monitor symptoms, BP, fluid intake. Advice on consumption of juices & soft drink.


  

       

Cont…

Alcohol
maintenance.

 Acamprosate:

Appear to reduce the effect of excitatory amino acids such glutamate, & modifies GABA neurotransmission .  Increase # of alcohol free days & the chance of subsequent complete abstinence.  Benefit may last for 1 yr after stopping it.  GI Side effects.

Cont…

Alcohol
Benzodiazepine antagonist, Flumazenil « Disulfiram
can reverse the acute central depressant effect of ethanol.


Inhibit ethanol metabolism  acetaldehyde accumulation gives toxic symptoms like: *headache *nausea, *flush, *tachycardia, *hyperventilation.  200-400mg/daily.

Also Naltrexone, (opiate receptor antagonist),

appear to block some of the reinforcing properties of alcohol.

Misused to obtain effects on mood.Opioids    Opiate: is a drug derived from alkaloids of the opium poppy. . (‫)نبات الخشخاش‬ Used primarily as analgesics.

e. Synthetic derivatives: compound with structures unrelated to morphines. ..e.     morphine. ( heroin) 3-methoxymorphine. II. Opioids Opioids include: Morphine analogues: compound closely related to morphine . ( mepyridine. (codeine)   pethidine..g.USA) fentanyl.g.  I. methadone. diamorphine.Cot.

.Cot. *sedation. unwanted effects: *respiratory depression.  1. κ (Kappa) receptors: contribute to *analgesia at spinal level. no contribution to dependence. *dependence) δ (Delta) receptors: important peripherally. *euphoria. Opioids Receptors: µ (mu) receptors: analgesic effects (through NMDA. N-methyl-D-asparatate). . may cause *dysphoria & *sedation. 2.. 3. may contribute to *analgesia.

..Cot. Opioids µ Analgesia -Supraspinal -Spinal -peripheral +++ ++ ++ δ ++ ++ ++ - κ + ++ + + +++ ++ + Respiratory depression +++ Pupil constriction GI motility Euphoria Dysphoria Sedation Dependence ** ++ ++ +++ ++ +++ .

nasally (snorted). smoked (inhalation) or of action: 3-4hr.  Dependence: physical dependence develop rapidly & characterize by a definite abstinence syndrome following withdrawal.  Route  Duration  Tolerance: developed rapidly..Cot.. Opioids of abuse: i. .v.

( fentanyl.V. ***I. heroin) which enter brain readily. Opioids cross placental barrier & may depress respiration in fetus. Small % of morphine cross BBB in contrast to more lipid-soluble drugs.. ***Pethidine does not cross placental barrier. it undergoes extensive 1st pass metabolism.Cot.. . Opioids  Kinetic:    Absorption of morphine from GIT slow. : 100% availability.

.Cot..metabolite excreted mainly in the urine & little in the bile. Opioids Morphine metabolized in the liver to glucuronides.  .

Piloerection. irritability. Fever. anxiety. Yawning. Opioids Withdrawal syndrome: (starts 8-10hrs after last dose. Sweating. cramp. Tachycardia. . Vomiting..Cot. Muscle aches Dysphoric mood Insomnia. Increase sensitivity to pain. diarrhea. BP (late stage) Craving for opioids. Nausea.. not life threatening)  Symptoms:                Signs: Pupillary dilatation. Restlessness.

Opioids Rx: Detoxification: 3 methods: Long acting opioid: methadone. *20-30mg as initial dose. .. clonidine analog.  Does not alleviate generalized ache & craving. Clonidine α-2 adrenergic agonist. tapered 20% / day during the course of detoxification.  No narcotic action. not addictive.Cot. with less hypotensive effect.       Centrally acting sympatholytic agent. Reduce central sympathetic outflow.. Mimic opioid effects alleviating many of withdrawal symptoms: autonomic symptoms. Lofexidine.   1. 2.

Cot. Theoretically attractive. 3. not found to be practical.. The technique proposed include acupuncture & several methods of CNS activation utilizing transcutaneous electrical stimulation. Opioids Involve activation of endogenous opioid system without medication..   .

can be given once daily or even less/ sublingually/ of dose 2-20mgdaily. methadone. Buprenorphine: partial opioid agonist. Methadone saturates the opioid receptors & prevent the desired sudden onset of CNS effects normally produced by i..Cot..v administration.  Maintenance:     . Opioids Orally daily dose of long acting opioid agonist.

Opioids heroin high normal sick Time (hrs( methadone .Cot...

Cot.. Opioids Narcotic antagonist: Naltrexone: long acting orally active pure opioid antagonist. Not satisfying craving or relieving protracted withdrawal symptoms.       . No dependence.. High affinity to µ -opioid receptor. utilized after detoxification for patients with high motivation to remain opioid-free.

Cot.. behavioral restlessness.           . dysphoria.. urinary retention. meiosis. postural hypotension. itching around nose. coma. Opioids Overdose: respiratory depression. Hyperactivity.

Repeated every 2 minutes as necessary until level of consciousness and respiratory rate increase & pupils dilate. Treat coma & hypotension.8-2 mg i.v. in severe cases does not usually respond to diuretic therapy. . Diagnostic test! Failure to respond to it indicate a cause other than morphine.. in adult). Non-carcinogenic pulmonary Oedema.Cot. ( O2 monitoring. CPAP and/or PEEP (positive end-expiratory pressure) may required. ABG) Naltrexone: reverse toxicity. Opioids Overdose Rx         Provide respiratory support.. used as bolus dose ( 0.

.

Referred to as “uppers  reverse the effects of fatigue on both mental and physical tasks.Caffeine.  temporarily increase alertness and awareness. Amphetamine.4 .1 Cocaine.Stimulants ”. .3 Nicotine.2 .

1 Dextroamphetamine Methylamphetamine (speed( (Cathinone (Khat Methylenedioxymethamphetamine (Ecstasy( .Amphetamine.

Smoked (e.O). Noradrenaline and Serotinine) in the bra ecrease MAO Destruction.Orally (P.g Methamphetamine .1 Mechanism of Action elease of Catecholamines ( Dopamine.V ( Amphetamine sulphate . Nasal Route (. Route of Abuse (.Amphetamine.I. elease of Noradrenaline from sympathetic nerves.

 Excitement. Arrhythmias .  Anorexia.Vasoconstriction .  Euphoria.  Stereotyped behaviour.Excess Noradrenaline Action on blood vessels and Heart: Tachycardia . :On Sympathetic nervous system .  Amphetamine Psychosis.Amphetamine Pharmacological Effects :On CNS Excess Dopamine action :  Locomotor Stimulation.  Insomnia.Increased BP .

 Depression.  Strong Desire for euphoric state.  Hungry.  Deep sleep. . Chiefly Psychological dependence.  Dysphoria.Amphetamine Tolerance and Dependence  Tolerance develop rapidly to peripheral sympathomimetic and anorectic effects  Dependence : due to  Unpleasant After-effects.  Withdrawal Syndrome :  Lethargy and Low energy.

Elimination : Excreted unchanged in the urine depending on the flow of urine an urine PH ( more in an acidic urine ). .Amphetamine Pharmakinetics Absorbed from GIT and Freely penetrates Blood-brain barrier( BBB). Plasma Half life is between 5-20 H. Absorbed from the nasal mucosa.

. Coronary and Cerebral thrombosis . petite Suppressant in Obesity ( Fenfluramine). MI. Vasculitis of cerebral and/or renal vessels .Acute Poisoning : arrhythmias . Chronic overdose : Psychotic state.Amphetamine Therapeutic uses ention Deficit/Hyperactivity Disorder ( ADHD) : Methylphenidate or Dexamphetam colepsy.

Depression : Antidepressants .Hyperpyrexia or Cardiac arrhythmias (.Amphetamine Psychosis : Haloperidol (antipsychotic .Amphetamine Treatment of Overdose Sedation ( Diazepam ) and Management of any .

gat.Leaves and stems of Khat plant . Route of abuse : Chewed . qat.Street names : kat. chat. tschat and mirraa . tohai.: Cathinone .

Cocaine ( Hydrochloride salt ( Cocaine.Plant Cocaine free base ( Crack ( .2 Alkaloid from the Coca .

Nasal route . Smoked (crack). Serotonine and Dopamine re-uptake into the presynap minals ntentiate and prolong the CNS and Peripheral actions of these Catecholamines. Sniffing .Cocaine Mechanism of Action ockade of Norepinephrine. IV. Route of Abuse .

 Arrhythmias.  High Blood Pressure.  Stereotyped behaviour.  Vasoconstriction.Cocaine Pharmacological Effects Similar to Amphetamine but more potent : ( Super Amphetamine On CNS :  locomotor Stimulation. performance and sense of well-being  Euphoria ( Limbic system ).  Sweating. ( Repeated doses On Peripheral Nervous System:  Tachycardia. Local Anaesthetic Properties ( Eye Surgery). Psychosis and Paronia. .  increase in self-confidence .

 Dependence: . same as Amphetamine : mainly Psychological Dependence  Withdrawal Symptoms ( Crash) : same as Amphetamine:  Dysphoria.Tolerance and Dependence  Tolerance Develops rapidly.  Hypersomnia.  Depression.  Irritability.Cocaine . .

Psychosis or Depression ( Antipsychotic or antidepressant .Cocaine te Overdose: Cardiac dysrhythmias.. Convulsions.premature labor. Propranolol or Calcium Channel-blocker .Sedation ( Diazepam (. coron and Cerebral thrombosis . Respiratory Depression. Foetal malformation Treatment (.

Caffeine-3 .

Caffeine Mechanism of Action (.Stimulate cellular Calcium influx .At High Concentration : Inhibits phosphodiesterase Intracellular cAMP .Blocking Adenosine Receptors (antagonist .

Caffeine Pharmacological effects Bronchial Relaxation( adenosine receptors). Psychotomotor Stimulant ( 3 cups of coffee = 200mg caffeine):  Reduced Fatigue.  Improved Concentration. .  Positive Inotropic and Chronotropic effects. Ordinary Consumption of Coffee: release Catcholamines :  Increase BP( Peripheral vasoconstriction).  Insomnia.

ncreases Gastric secretion. ( Reduced tubular reabsorption of Na . Metabolized in the liver and excreted through urine.Cont ncreases Diuresis. (peptic ulcer).Caffeine . Half Life ( 2-12 H). weak Thiazide Action. Pharmacokinetics Well Absorbed orally.. . Can cross the placenta.

 Withdrawal Symptoms ( 5 or more Cups) :  Lethargy.  Headace. .  Irritability.Caffeine Tolerance and Dependence Slight Tolerance to the effects of caffeine ( on all systems) occur Dependence :  Psychological and Physical.

 Insomnia.Caffeine !!!!! : But : Excessive Prolonged Consumption  Anxiety. Therapeutic use n combination with Ergotamine or aspirin ( for Migrain .  Restlessness.  Tremors.  Cardiac Extrasystoles.

(Pipe . Cigar( Nicotine Is A Killer . Cigarette.

Cigar .

Pipe Cigarette .

 Sweating. .  Increase Cardiac Output.Nicotine Mechanism of Action Nicotinic Ach Receptors in autonomic ganglia and adrenal gland ease of Catcholamines .Serotonin. ADH  Tachycardia.  Increase Gastrointestinal motility.  Increase BP.

Pharmacokinetics An average cigarette contains 0. Decreased appetite.Cont : Nicotinic Ach Receptors in brain++ Arousal ( small doses). Elimination : in urine depending on pH. Convulsions and coma (a high doses). . Half life is 2 H. Pleasant feeling.8 g of Tobacco and 9-17 mg of Nicotine of which 10% is absorbed. ++ ADH  decrease Diuresis.Nicotine .

 Sleep Disturbance. Dependence :  Psychological and Physical.  Withdrawal Symptoms ( lasts for weeks):  Irritability. .  Increase Appetite.  Impaired Psychomotor performance.Nicotine Tolerance ad Dependence Tolerance develops rapidly.

.Nicotine Long-Terms Risks Cancer: Bronchogenic cancer and cancer of mouth and Throat.  Stillbirth. Dangerous effects in pregnancy: risk of :  Abortion. Chronic Obstructive Lung Disease.  Neonatal Death. Coronary Heart disease.

Reduce withdrawal effects .Nicotine resin contained in Chewing gum (Nicorette .Nicotine Treatment :Nicotine Replacement Therapy (.Nicotine Transdermal patches ( : Clonidine (α2 adrenoceptor agonist .

مضغة‬ Pan parag. جوتكاه‬ tambac((‫تمباك‬ Others: pan(‫.Oman and Tobacco Unsmoked Tobacco.g. E. )بان‬bangi( (‫بانجي‬ Tambacu((‫ .تمباكو‬Alnshooq( (‫النشوق‬ Alshma((‫الشمة‬ ALsubari ((‫السوباري‬ . guthka(‫)بانبراك.: Afdhal((‫أفضل.

Between the lips and gingiva.مضغة‬ . or between cheek and gingiva- Afdhal((‫أفضل.:Rout of abuse .

Lime . Betel nut.Tombac((‫تمباك‬ Tobacco.

‫بانبراك‬ ‫)جوتكاه‬ .Pan parag. guthka(.

One head of Muasel = 20 regular cigarettes .Shisha .

Because he keeps coughing the whole Night .Because he visits a new doctor everyday . Because he dies younger .A Smoker is not affected by Normal Aging .. A smoker is not visited by his relatives or other people .A smoker always adds a person to his friends list . Thieves don’t steal his house .Because of his bad smell .

Khalid Al-Saidi .

The outline       Hallucinogens: LSD Cannabis Inhalants Date rape drugs Conclusion Clinical case .

  . Action: agonist effect at presynaptic 5HT receptors in the CNS. Duration of action: effect start after 40-60 min & lasting for 6-8 hrs.LSD   LSD: lysergic acid diethylamide. Route of abuse: usually p.o.

depression. flushing. lacrimation & hyperreflexia. Mood changes including elation. & sometimes a feeling of panic. paranoia. increased BP & pulse.LSD Pharmacological effects:    Produces perceptual distortions & sometimes hallucinations. Pupillary dilation. . salivation. intense arousal.

 . Diazepam may be given to control severely agitated drug abuser.LSD  Tolerance does develop to the behavioural effects but no withdrawal syndrome has been observed.

With high doses: ataxia. Intoxication an be prolonged & hazardous with agitation. convulsions & an adrenergic crises. Haloperidol or diazepam may be given for treatment. aggressive behavior & hallucination together with nystagmus & raised BP.Phencyclidine  PCP or ‘angel dust’ is a synthetic hallucinogen with dangerous effects.    . muscle rigidity.

The resin scrapped off the plant is known as hashish.Cannabis  Obtained from the plant Cannabis sativa. Two forms: The preparation that are smoked are called marijuana & consist of crushed leaves & flowers.  .

 . Receptors: CB1-receptor: central & peripheral neurons. CB2-receptor: immune cells.Cannabis Mechanism of action:  Active compound: tetrahydrocannabinoil (THC).

. The physical signs include reddening of the conjunctiva. It distorts experiences of time & space. Euphoria is common. Cognitive function impaired. dry mouth & tachycardia. Sensations become more vivid. Recent memory & attention impaired.Cannabis Pharmacological effects:        They commence within minutes of starting to smoke & last 2-3 h.

but it also disappears rapidly. .  Psychological dependence can develop but physical dependence does not occur.Cannabis  Tolerance develops rapidly.

Cannabis  ‘A motivational syndrome’  Cannabinoids & skilled tasks .

  .Cannabis Clinical use:  As antiemetic in cancer patient. Muscle spastisity in multiple sclerosis. Chronic pain & migraine.

such as toluene.   . such as amyl or butyl nitrate.Inhalants  Industrial solvents. Organic nitrates. including a variety of hydrocarbon. Aerosol propellants. such as fluorocarbons.

Inhalants Acute intoxication    Complications       Slurring of speech Disorientation Uncoordination of gait Nausea & vomiting Coma Visual hallucinations Liver & kidney damage Peripheral neuropathy Perceptual disturbances Tolerance & Psychological dependence .

Date rape drugs  Sometimes used to assist a sexual assault. Examples: GHB (gamma hydroxybutyric acid) Rohypnol (flunitrazepam) Ketamine (ketamine hydrochloride)  .

 . including water. colorless & odorless & can be crushed & added to any drink. It is tasteless. without detection.Rohypnol  The predominant clinical manifestations are drowsiness. impaired motor skills & anterograde amnesia.

. It can cause long term health hazards.Conclusion       Drug abuse is a serious health problem. Drugs should be prescribed only if necessary & with caution. It can result in death due to overdose or withdrawal syndrome. It can lead to Deterioration in social life & occupational performance. Legalizations provide no guarantee for safety.

C.Clinical case  M. was hospitalized because of breathing difficulties. . did not vomit & did not have diarrhea. He was hospitalized after further 2h. At admission into hospital he said that 2h following his last dose of heroin he usually gets these breathing difficulties & he asked for help from his GP who recommended that he should be hospitalized.C. M.

Clinical case What are the causes of his respiratory difficulties?  Acute intoxication (overdose): Unexpected purity of street drug Reduced tolerance Suicide attempts  Lung edema: hypersensitivity. product impurity or pulmonary embolism  Other complications: septic embolism .

C. cannabis. is a 42 yrs old man dependent on heroin. amphetamine) but he always returned to heroin. various medications (benzodiazepine. At various times he had experimented with other kinds of psychotropic agents: alcohol.Clinical case Personal history: M. . Originally he had used heroin intravenously. by snuffing).e. cocaine. Because of fear of AIDS he changed to the intranasal method (i.

He is still living with his parents. .Clinical case Personal history: He refused treatment by psycho-analysis or psychotherapy as he believes these “fundamentally wrong”. He barely copes with his occupation in information science.

The heart appeared to be without any pathological findings.  . cyanosis. Body temperature 36. dry. Crepitations over both lung bases. The skin is lightly cyanotic.Clinical case Examination:     Polypnoea. with usual appearance without signs of dehydration.6 Cº. bilateral miosis.

Clinical case Laboratory examination:  pO2 = 8.6 kPa (65 mm Hg) pCO2 = 4 kPa (30 mm Hg)  .

Clinical case  Further examination & treatment were carried out. Lung X-ray examination: lung oedema of non-cardiogenic origin (caused by opiates). . Naloxone was administered to the patient but it has no effect on his breathing difficulties.

Changes of lung X-ray examination lasted longer than 24h. the cyanosis decreased & monitored values of the blood gases slowly returned to the normal values. After 5h the breathing difficulties decreased . .Clinical case  The patient’s treatment is now proceeding: the patient is given oxygen (6L/min) by inhalation.

Bennett.emedicine. Moore. M.References       Bertram G. K. Katzung. Brown. Dale. P. 8th ed.wikipedia. Basics & clinical pharmacology. http://www. M. J.com http://en. N.org HeroinAbuse. P. Pharmacology. 5th ed. M. Clinical pharmacology. M. 9th ed.Net . P. H. Ritter. Rang. J.

Ragini Vaishnav 2007© ‫جميع الحقوق محفوظة‬ (GROUP A) ‫مع تحيات‬ .Next week Management of Acute Poisoning The End Drugs of Abuse Presented by Abu Musaab Abdullah Al-Omairi Abu Al-Yaman Adil Al-Ghafri Abu Nawwaf Ahmed Al-Mazroui Abu Al-Waleed Khalid Al-Saidi Supervisors Dr. Aly Abdelrahman Dr.

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