IVMS-CNS Pharmacology- Intro to Drugs of Abuse II-Opioids
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
5. 5
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
7. 7
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)
8. 8
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
9. 9
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
10. 10
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
11. 11
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
12. 12
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
13. 13
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
14. 14
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
15. 15
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
16. 16
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
17. 17
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
18. 18
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
19. 19
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
20. 20
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
21. 21
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
22. 22
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
23. 23
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
24. 24
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
25. 25
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
27. 27
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
28. 28
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