Drugs of Abuse

DR. SAZAN D. SAEED

PHD. IN TOXICOLOGY
 DRUGS OF ABUSE

⚫ Opioids
⚫ CNS depressants
⚫ CNS stimulants
⚫ Hallucinogens
⚫ Mind altering drugs
 What are the commonly abused prescription
drugs?
Although many medications can be abused, the following three
classes are most commonly abused:
• Opioids—usually prescribed to treat pain

• Central nervous system (CNS) depressants—used to treat

anxiety and sleep disorders

• Stimulants—most often prescribed to treat attention deficit

hyperactivity disorder
 All Abused Drugs and
Substances Enhance
Dopamine Activity
(particularly related to
pleasure,
motor, and cognitive function)
•Main addition pathway is
Dopaminergic pathway
•Other pathways also involved!
 striatum
frontal hippocampus
cortex

substantia
nigra/VTA

nucleus
accumbens

raphe
Neuronal structure

(receiving)

(sending)

www.drugabuse.gov
 vesicle
stimulation Drug :
• cocaine transporter
• ritalin
Vmat

/serotonin

DA/5HT

Neuronal terminal
 transporter

Vmat serotonin/

● Release DA without stimulation

from vesicles and reverse
transporter
Drug Types:
DA/5HT
• Amphetamines
•Methamphetamine
•MDMA (Ecstasy)
methylenedioxy-methamphetami
ne
 Opiates and Opioids
Opiates: are a group of naturally occurring compounds derived from the juice of the
poppy plant Papaver somniferum
Morphine is the classic opiate derivative used widely in medicine; Heroin is a
well-known, highly addictive street narcotic.
The term opioids refers to medication that relieve pain
Natural : morphine, heroin, codeine
Semi-synthetic : Buprenorphine, hydrocodone, hydromorphone, oxycodone,
oxymorphone
Synthetic: diphenoxylate, fentanyl, meperidine, methadone, propoxyphene and
tramadol.
A wide variety of prescription medications contain opioids, often in combination with
aspirin or acetaminophen
 Continue.,

Dextromethorphan: is an opioid derivative with potent antitussive but

no analgesic or addictive properties
Tramadol: is an analgesic that is unrelated chemically to the opiates
but acts on mu-opioid receptors and blocks serotonin reuptake
Tapentadol (Nucynta):is a new mu-opioid agonist that also inhibits the
reuptake of norepinephrine.
 Mechanism of toxicity

⚫ In addition to enhance dopamine

activity.
⚫ Opioids share the ability to stimulate
specific opioid receptors in the CNS,
causing sedation and respiratory
depression
⚫ Cause of Death
⚫ Death results from respiratory
failure, usually as a result of apnea
or pulmonary aspiration of gastric
contents
 Diagnostic test

⚫ 1. Pinpoint pupils
⚫ 2. Respiratory and CNS depression

⚫ Pregnancy category
⚫ Almost all the opioid are category C,
⚫ Meperidine B→D,
⚫ Oxycodone B→D,
⚫ Oxymorphone B→D
 Clinical presentation

Mild-moderate overdose Higher doses Withdrawal syndrome

• Lethargy • Anxiety
• Coma
• Pinpoint • Goosebumps
• respiratory • Heightened sensation of
• Blood pressure ↓
depression, pain
• HR ↓
• ↓ bowel motility
• apnea • Abdominal cramps
• Muscles are usually • sudden death. • Diarrhea
flaccid • Insomnia

Seizures mat occur with(codeine Cardiotoxicity: propoxyphene

dextromethorphan, meperidine,
propoxyphene, and tramadol
Drug Type of activity Usual dose Duration of
analgesia
Buprenorphine Agonist 24-48
Butorphanol Mixed 3-4
Codeine Agonist 4-6
Fentanyl Agonist 0.5-2
Heroin Agonist 3-4
Hydrocodone Agonist 4-8
Hydromorphone Agonist 4-5
Meperidine Agonist 2-4
Methadone Agonist 4-8
Morphine Agonist 3-6
Oxycodone Agonist 4-6
Pentazosine Mixed 2-3
Propoxyphene Agonist 4-6
Tramadol Agonist 4-6
Just for information
 Treatment of opioid toxicity

⚫ 1. Maintain an open airway and assist ventilation, administer supplemental

oxygen.
⚫ 2. Treat coma, seizures, hypotension, and non-cardiogenic pulmonary edema.
⚫ Antidotes:
⚫ 1. Naloxone 0.2-0.4 mg IV, repeated dose 2-3 minutes if there is no response ,
up to a total dose of 10–20 mg if an opioid overdose is strongly suspected
⚫ 2. Nalmefene may be given in doses of 0.1–2 mg IV, with repeated doses, up
to 10–20 mg if an opioid overdose is strongly suspected.
- Although the duration of effect of nalmefene is longer than that of
naloxone, it is still much shorter than that of some opioids
⚫ 3. Sodium bicarbonate: effective for QRS prolongation or
hypotension associated with propoxyphene poisoning.
⚫ Fluid support – Increases excretion
⚫ Other ways for treating the pain (analgesic)
⚫ Decontamination
⚫ 1. Prehospital Administer AC if available. Do not induce vomiting,
because If a person vomits, they may be unable to effectively clear
their airway, leading to aspiration of vomit into the lungs.
⚫ 2. Hospital. Gastric emptying is not necessary. Consider
whole-bowel irrigation after ingestion of sustained-release products
⚫ Enhanced elimination : Because of the very large volumes of
distribution of the opioids and the availability of an effective
antidotal treatment, there is no role for
enhanced elimination procedures.
 Initial adult dose 0.04mg Initial pediatric dose 0.1mg/kg

Administer 0.5 mg of naloxone

If increase in RR doesn't occur in 2-3 min

Administer 2 mg of naloxone

If increase in RR doesn't occur in 2-3 min

Administer 4 mg of naloxone

If increase in RR doesn't occur in 2-3 min

Administer 10 mg of naloxone
RR: Respiratory Rate
If increase in RR doesn't occur in 2-3 min

Administer 15 mg of naloxone
 Medication Assisted Treatment (MAT) of abused persons

1. Behavioral therapy (extremely important)

2. Methadone (Full Agonist): Activates opioid receptors in the brain,

fully replacing the effect of whichever opioid the person is addicted to
Advantage: eliminates withdrawal symptoms and relieves drug cravings
Dose 10-30 mg

3. Buprenorphine (Partial Agonist): Activates opioid receptors in the

brain, partially replacing the effect of whichever opioid the person is
addicted to
Advantage: Like methadone, it can reduce cravings and is well
tolerated by patients.
The target dose for the first day is usually 8 to 12 mg
 • CNS depressants
• CNS depressants, are substances that can slow brain
activity. This property makes them useful for treating
anxiety and sleep disorders.

• 1. Benzodiazepines:
• Diazepam and Alprazolam (Xanax).
• The more sedating benzodiazepines are Triazolam and
Estazolam are prescribed for short-term TX of sleep
disorders.
• Non-benzodiazepine sleep
• The medications:
• zolpidem, eszopiclone and zalepon
• They have a different chemical structure, but act on some of
the same brain receptors as benzodiazepines.
• They are thought to have fewer side effects and less risk of
dependence than benzodiazepines.

2. Barbiturates
Used as sedative hypnotic
• Mephobarbital, Phenobarbital (Luminal Sodium), and
Pentobarbital sodium are still used in surgical procedures and
for seizure disorders
 Is it safe to use CNS depressants with other
medications?
•Typically, they should not be combined with any other
•medication or substance that causes CNS depression,
including prescription pain medicines (Opioids), some
OTC cold and allergy medications (Antihistamine), and
alcohol.
•Using CNS depressants with these other
substances—particularly alcohol— can affect
•heart rhythm, slow respiration, and even lead to death.
 Stimulants

⚫ What are stimulants?

⚫ Stimulants increase alertness, attention,
and energy, as well as elevate blood
pressure, heart rate, and respiration.
⚫ Stimulants historically were used to treat
asthma, obesity, neurological disorders
⚫ Stimulants are prescribed to treat only a few
health conditions:
⚫ ADHD
⚫ Narcolepsy (excessive sleepiness)
⚫ Depression—in those who have not responded
to other treatments.
 CNS Stimulants

⚫ Amphetamines
⚫ Methamphetamines
⚫ Cocaine
⚫ Nicotine, caffeine, energy drinks
⚫ Other stimulants such as:
⚫ dextroamphetamine (Dexedrine )
⚫ Methylphenidate (Ritalin ).
 Amphetamines

Amphetamines are powerful

CNS stimulant that increase
activity in the CNS, and speed
up the way the human body
works.
Amphetamines are generally a
white or off-white powder that
can be ingested orally, snorted,
or injected.
 Methamphetamine

♓ Methamphetamine is a powerful,
synthetic CNS Stimulant.
♓ Methamphetamine is generally a white
or off-white powder that can be ingested
several different ways: Crystal Meth
✶ 1. Orally – In a pill form
✶ 2. Snorted – This can cause severe damage
to the interior and exterior of the nose.
✶ 3. Injection - IV and IM
✶ 4. Smoked – Methamphetamine is
sometimes smoked by itself or with
marijuana.
 Cocaine

Cocaine is one of the most popular

drugs of abuse, it is a bitter, white,
odorless, crystalline drug.
Cocaine is classified as a CNS
stimulant.
Cocaine mostly found in South
America.
Street name : snow , dust, candy
Cocaine snorted, smoked, or injected IV.
 CNS stimulants
⚫ Dextroamphetamine (Dexedrine) and
methylphenidate (Ritalin) are used for the treatment
of narcolepsy and for attention-deficit disorders in
children
⚫ Several amphetamine derivatives like:
benzphetamine, diethylpropion, phendimetrazine,
phenmetrazine, and phentermine used to treat
obesity
⚫ Modafinil used for treatment of narcolepsy
⚫ Atomoxetine used to treat ADHD
⚫ Newer synthetic analogs, such as
3,4-methylenedioxypyrovalerone and
various derivatives of methcathinone
(chemically related drugs with
amphetamine-like effects)
⚫ they becoming popular drugs of abuse,
often sold on the Internet as “bath salts”
with names such as “Ivory Wave,”
“Bounce,” “Bubbles,” “Mad Cow,” and
“Meow Meow.
 Mechanism of toxicity
⚫ Amphetamine and related drugs
⚫ Activate the sympathetic nervous system via CNS stimulation
⚫ Peripheral release of catecholamines
⚫ Inhibition and reverse neuronal reuptake of catecholamines
⚫ Inhibition of monoamine oxidase. Amphetamines, particularly MDMA, also
cause serotonin release and block neuronal serotonin uptake.
⚫ The various drugs in this group have different profiles of catecholamine and
serotonin action, resulting in different levels of CNS and peripheral stimulation
⚫ Cocaine, dextroamphetamine and methylphenidate: Increases dopamine release and
inhibit its uptake
● Amphetamine, Methamphetamine and MDMA: Release dopamine without
stimulation from vesicles and reverse transporter, and have different effect on catecholamine as
discussed previously
Mechanism of toxicity
 Clinical presentation

Acute
⚫ . CNS effects of intoxication :
Euphoria, talkativeness, anxiety,
restlessness, agitation, seizures, and
coma.
Intracranial hemorrhage may occur
owing to hypertension
Acute peripheral manifestations :
Sweating, hyperthermia, tremor,
muscle rigidity, tachycardia,
hypertension, acute myocardial
ischemia, and infarction
⚫ Death may be caused
by:
⚫ Arrhythmia
⚫ Status epilepticus,
⚫ Intracranial
hemorrhage
⚫ Hyperthermia.
 Chronic effects

⚫ Extreme weight loss,

⚫ Cardiomyopathy,
⚫ Hypertension
⚫ Dental changes
⚫ Stereotypic behavior (picking at the
skin)
⚫ Paranoia, and paranoid psychosis.
⚫ Psychiatric disturbances may persist
for days or weeks.
⚫ After cessation of habitual use,
patients may experience fatigue,
hypersomnia, hyperphagia, and
depression.
 Treatment

A. Emergency and supportive measures

1. Maintain an open airway and assist ventilation if necessary.

2. Treat agitation, seizures, coma, and hyperthermia
3. Continuously monitor the temperature , , other
vital signs and the ECG for a minimum of 6 hours.
B. Specific drugs and antidotes
1. Agitation: BDZ are usually satisfactory
a. Midazolam, 0.05–0.1 mg/kg IV over 1 minute, or 0.1–0.2 mg/kg IM
b. Lorazepam, 0.05–0.1 mg/kg IV over 1 minute
c. Diazepam, 0.1–0.2 mg/kg IV over 1 minute
⚫ 2. Hypertension :is best treated with sedation and, if this is
not effective, a parenteral vasodilator such as
phentolamine or nitroprusside.
⚫ 3. Treat tachyarrhythmias with propranolol or esmolol.
⚫ C. Decontamination
⚫ Administer AC, if available. Do not induce vomiting
because of the risk of abrupt onset of seizures.
⚫ Hospital. Administer AC. Gastric emptying is not necessary
if activated charcoal can be given promptly.
⚫ D. Enhanced elimination
:Dialysis and hemoperfusion are not effective.
 Is it safe to use stimulants
with other medications?
Patients should be aware of the dangers associated with mixing
stimulants and OTC cold medicines that contain decongestants
( phenylephrine, pseudoephedrine)
, as combining these substances may cause blood pressure to
become dangerously high or lead to irregular heart rhythms.