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1. CNS Pharmacology-
Introduction to Drugs of Abuse II/Opoids
Prepared and Presented by:
Marc Imhotep Cray, M.D.
Professor Basic Medical Sciences
Clinical:
E-Medicine Articles
Opioid Abuse

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OPIOIDS or NARCOTICS
I. Morphine
II. Codeine
III. Meperidine
IV. Methadone
V. Designer Opioids

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I.
Morphine, Heroin, Hydromorphone,Oxymorp
hone
A. Pharmacology
- Heroin is very lipid soluble
- Short half-life (t½ = 3 min)
- Heroin  6-mono-acetyl morphine 
morphine
OPIOIDS or NARCOTICS

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Desirable Effects:
 Euphoria
 Sedation
 Relief of anxiety and
various other forms of
distress
 Analgesia
 Depression of cough
reflex*
Subjective CNS effects:
 Drowsiness
 Difficulty concentrating
 Apathy
 Decreased physical
activity
 Lethargy
 Extremities feel heavy and
the body feels warm
OPIOIDS or NARCOTICS

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Undesirable Effects:
Dysphoria Dizziness Nausea
Vomiting Constipation* Biliary tract spasm
Urinary retention
OPIOIDS or NARCOTICS

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OPIOIDS
1).Psychological
dependence
 I.V. use preferred by most
users => “rush” or “high”
 Oral abuse => meperidine
 Emotional or motivational
symptoms, “craving”.
 Iatrogenic addiction
2).Physical
dependence
 May develop on
repeated use of
therapeutic doses
 Narcotic Abstinence
Syndrome
(Withdrawal)

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 Withdrawal, onset related to time-effect
curve and t½ of narcotic
 6-8hr =>drug seeking behavior, restless, anxious
 8-12hr => Pupils dilated, reactive to light; increased
pulse rate, blood pressure, yawning; chills; rhinorrhea;
lacrimation; gooseflesh; sweating; restless sleep.
 48-72 hrs (peak) => All of the above plus muscular
weakness, aches (cramps) and twitches;
nausea, vomiting and diarrhea;  temperature and
respiration rate elevated; heart rate and blood pressure
elevated; dehydration
OPIOIDS

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 Withdrawal, onset related to time-effect
curve and t½ of narcotic
Not life threatening, no convulsions, no
delirium, no disorientation
Treatment of withdrawal: symptoms =>
clonidine
OPIOIDS

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B. Concurrent or Substitute use:
 Alcohol, sedatives or
cocaine/amphetamines
C. Tolerance
 Yes, develops to all effects except
constipation and pupillary effects
 Cross-tolerance and cross-
dependence with other narcotics
(Implication in narcotic addict =>
need to increase dose to experience
euphoria)
 High level of
tolerance is possible;
huge amounts of drug
can be tolerated after
chronic use; potential
for overdose if relapse
occurs and addict
resumes with same high
level of drug
 Implications for chronic
administration for pain
OPIOIDS

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D. Toxicology
1.Tissue and organ toxicity
- “Heroin lung” with acute overdose
- No apparent tissue damage
2. Psychic toxicity
- Acute and chronic drive reduction
3. Behavioral toxicity
- Criminal behavior to obtain drugs
4. Associated
diseases/Death
- Unsterile syringes:
AIDS, hepatitis, SBE,
malaria, tetanus,
localized infections,
pulmonary infiltration
of contaminants
Neuropathies, Violent
deaths
OPIOIDS

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E. Acute Intoxication/Overdose
1. Disruption of central control of
peripheral sympathetic activity
- Respiratory depression =>
apnea=> DEATH
- Circulatory depression => BP
- Pupils constricted (may be
dilated with meperidine)
- Convulsions with
propoxyphene
and meperidine
- - Arrhythmias w
propoxyphene
- Pulmonary edema
-  Reflexes
OPIOIDS

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E. Acute Intoxication/Overdose
(con’t)
2. CNS depression
- Euphoria/dysphoria =>drowsiness
=>sedation => coma
Treatment of overdose => Naloxone
(Narcan ®) I.V. (0.1-0.4 mg) repeated
as necessary
Short acting opioid antagonist (1-2 hrs).
Give every 30 minutes until patient is
controlled
Follow by methadone
Nalmefene could also
be used, has longer
half-life
Also used to control
and reverse effects
of therapeutically
administered
narcotics
(anesthesia and
labor)
OPIOIDS

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F. Treatment of
Depenndence
 Narcotic dependence is
one of very few cases
where there are
partially effective
pharmacological
therapies
1. Opioid replacement
a. Methadone, Dolophin®
 Long half-life produces a
longer but less stressful
withdrawal (although
more prolonged).
 Onset =>24hrs, peak
=>5-7 days
 Lessens the “highs” and
“lows” of withdrawal
 Oral administration
OPIOIDS

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b. LAAM (L-a-acetyl methadol, methadyl
acetate)
 Structurally similar to methadone.
 Longer-acting opiate
 Taken orally in liquid form, lasts 72hrs (visits 3 X a
week)
 “Take home" medication
OPIOIDS

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OPIOIDS
c. Buprenorphine
 Partial agonists which substitutes for low
doses of opioids but antagonizes high
doses
 Can be administered sublingually every
24-48 hours as an alternative to
methadone

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F. Treatment of Dependence
 Major problem in detoxification and
maintenance of abstinence is the
motivational component of the CNS effect,
which is responsible for the “drug craving”
sensations,
 Also conditional dependence and social
factors play an important role.
OPIOIDS

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Opiate Antagonists
cause precipitated
abstinence
Naltrexone:
 Used for the long
term maintenance
of abstinence
 Long half-life, oral, 3
times a week
Naloxone:
 Use in life-
threatening
situations for
overdose
 Short half life (1-2-hrs)
control and reverse
effects of
therapeutically
administered narcotics
(anesthesia and labor).
OPIOIDS

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II.Codeine (Methylmorphine); Dihydrocodeine; Hydrocodone
(Dicodid®, Hycodan®); Oxycodone (Percodan®).
A. Pharmacology
 << Potent than morphine IM, but almost never
administered parentally
 "Weak" opioids.
 Used as a cough suppressants (antitussive) and
combined with aspirin and acetaminophen as painkillers.
 Dependence liability < < than morphine
OPIOIDS

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III. Meperidine (Demorol®); Alphaprodine,
(Nisentil®)
A. Pharmacology
- Less potent than morphine
- IM More rapid onset, shorter duration Similar
to heroin
- Used in anesthesiology
- Dependence liability - Same as Morphine
OPIOIDS

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IV. Methadone
A. Pharmacology
 Pharmacodynamic profile very similar to morphine
 Longer acting (10 hrs) vs Morphine (4-5 hrs)
 Equipotent and equieffective to morphine
 Tolerance and dependence develop more slowly than with
morphine
 Withdrawal signs and symptoms are milder but more
prolonged
 Use for detoxification or maintenance of a heroin addict
OPIOIDS

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IV. Methadone
B. Concurrent or substitute use - Yes Other
narcotics
C. Tolerance: Same as Morphine, Cross-
tolerance with other narcotics
D. Acute intoxication/Overdose: Similar to other
narcotics
E. Withdrawal: Same as Morphine
F. Treatment: None
G. Mechanism of action: m opioid receptors
OPIOIDS

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V. Designer Opioids
a. MPTP
(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).
A meperidine/heroin-like drug, MPTP was synthesized in the
1980’s. It contained MPP+ impurities that cause Parkinson's
like-symptoms in the young adults who used it by destroying
DA neurons.
b. Fentanyl (Sublimaze)
China White: alpha-methyl fentanyl => deaths by
overdose
6000 times more potent than morphine
OPIOIDS

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G. Mechanism of action
1. Anatomy of m opioid receptors: nucleus
accumbens (N. Acc.), ventral tegmental area
(VTA), caudate, thalamus, cortex, spinal cord2.
Actions in thalamus => Sensory modalities.
3. Actions in spinal cord => Analgesia
4. Actions at Mesolimbic dopaminergic system =>
Reward. Inhibit the release of GABA at the VTA
Desinhibition of DA =>DA activity
OPIOIDS

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Mechanism of action
Opioids act at the Mesolimbic Dopaminergic
System
=> Reward Center of the Brain.
Inhibit the release of GABA at the VTA

Desinhibition of Dopamine neurons

DA activity
OPIOIDS

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Drugs and Neurotransmitters & Mental
Disorders Interactive Tutorials and
Animation Learning Tools
 Psychotropic Medications and Neurotransmitters
Wisconsin Online
 Alcohol and the brain from PBS
 The Effect of Drugs and Disease on Snaptic
Transmission Harvard Education
 Nicotine Patch by Nucleus Communications
 GABA Inhibition of Glutamate Bay Area Pain Medical
Associates
 Acute Pain Bay Area Pain Medical Associates
 How Drugs Affect Neurotransmitters INMHA

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Drugs and Neurotransmitters & Mental
Disorders Interactive Tutorials and
Animation Learning Tools
 Schizophrehia UNIVERSITY OF CENTRAL LANCASHIRE
 Epilepsy UNIVERSITY OF CENTRAL LANCASHIRE
 Pharmacologic Action of Meth RnCeus.com
 How is Pain Produced University of Edinburgh
 How Much Alcohol can YOU TAke BBC
 The Brain: Understanding Neurobiology Through the Study of Addiction
National Institutes of Health
 The Science of Addiction University of Utah, Genetic Science Learning
Center
 Stimulants and Antidepressants Dr. Ian Winship of the University of
Alberta
 Tranquilizers and CNS Depressants Dr.Ian Winship of the University of
Alberta
 Genetics of Addiction Genetics Science Learning Center

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eMedicine Articles on Addiction
 Alcohol-Related Psychosis
 Alcoholism
 Amphetamine-Related
Psychiatric Disorders
 Caffeine-Related Psychiatric
Disorders
 Cannabis Compound Abuse
 Cocaine-Related Psychiatric
Disorders
 Hallucinogens
 Inhalant-Related Psychiatric
Disorders
 Injecting Drug Use
 Nicotine Addiction
 Opioid Abuse
 Phencyclidine (PCP)-Related
Psychiatric Disorders
 Sedative, Hypnotic,
Anxiolytic Use Disorders
 Stimulants
 Substance-Induced Mood
Disorders: Depression and
Mania