Opioid Analgesics
Basic Pharmacology Block
PDNT/PMED.PMSC/PPHR -213
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Objectives
1. Identify the major classes of analgesics.
2. Identify the classes of opioid drugs and their receptors.
3. Recognize the different opioid agents and their indications.
4. Recognize the features and differences of opioid drugs.
5. List the side effects and contraindications of opioid drugs.
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Analgesics
• Analgesics are divided into 3 groups:
I. Non opioids (non-narcotic) NSAID, analgesic activity is
relatively weak.
II.Opioids (narcotic)
III. Adjuvants (diverse group of drugs whose analgesic effect
is secondary to their primary effect)
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Analgesics
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Opioids
Opioids are natural or synthetic compounds that
produce morphine-like effects. The term opiates is
reserved for drugs, such as morphine and codeine,
obtained from the juice of the opium poppy.
• The opioid (narcotic) analgesics, along with the
NSAIDs, are mainstay agents to manage pain.
• However, all narcotic analgesics have a liability for
abuse, physical dependence and addiction.
• Therefore, narcotic analgesics are all controlled
substances.
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Opioids
1. Morphine and codeine: in the juice of the opium poppy
2. Endogenous opioid peptides
– They are released from nerve endings, modulate
transmission in the brain and spinal cord.
• All other opioids are prepared from either morphine
(semisynthetic opioids such as heroin) or they are
synthesized from precursor compounds (synthetic opioids
such as fentanyl)
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Endogenous opioid peptides
1. Endorphins–primary peptide is b-endorphin found in the
hypothalamus and other brain nuclei and the anterior pituitary
and released in response to stress
2. Enkephalins–widely distributed in the CNS and inter neurons
especially those mediating pain pathways
3. Dynorphins–widely distributed in the CNS; associated with
spinal cord mediated pain pathways
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Opiate Receptors
Opioids interact with protein receptors
on the membranes of certain cells in
the CNS, on nerve terminals in the
periphery, and gastrointestinal tract
(GIT).
• The major effects of the opioids are
mediated by three major receptor
families: μ (mu), κ (kappa), and δ Image borrowed from Wyeth library
(delta).
* ORL1 is a new opioid receptor
found.
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Opiate Receptors
Each receptor family exhibits a different specificity for the drug(s) it
binds.
The analgesic properties of the opioids are primarily mediated by the
μ receptors.
Binding of opioids to their receptors inhibit calcium channel and
open potassium channels. The net result is a decrease in the release
of some pain mediators such as dopamine, serotonin and substance
P, resulting in blockage of transmission.
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Opioid Classification
Opioid analgesic and antagonists
Strong agonist Moderate agonists Mixed agonist-antagonist Antagonists
1. Morphine 1. Codeine 1. Buprenorphine 1. Naloxone
2. Fentanyl 2. Pentazocine 2. Naltrexone
3. Meperidine 3. Nalbuphine 3. Nalmefene
4. Methadone.
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Pharmacological actions of
Opioids
• Desirable:
– Analgesia
– Cough suppression
• Undesirable:
– Euphoria
– ↓ Respiration
– Sedation
– Immunosuppression
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Pharmacological actions of
Opioids
• Sedation and euphoria
– Occur at doses below those required for maximum analgesia
• Respiratory depression
– Inhibition of the respiratory center
• Antitussive actions
– Suppression of the cough reflex
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Pharmacological actions of
Opioids
• Nausea and vomiting
– Activation of chemoreceptor trigger zone
• Miosis
– Causes pupillary constriction, Except meperidine.
• Constipation (GI effects)
– Decreased intestinal peristalsis
– Basis for use as antidiarrheal drugs
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Opioid Therapeutic Uses
a) Analgesia
b) Treatment of diarrhea: Morphine decreases the motility of
intestinal smooth muscle. [This can cause constipation]
c) Antitussive: they suppress the cough reflex. Codeine and
dextromethorphan are more widely used to relief cough.
d) Some IV opioids are used in general anesthesia.
e) Treatment of acute pulmonary edema:
– IV morphine dramatically relieves dyspnea caused by
pulmonary edema associated with left ventricular failure,
possibly by its vasodilator effect.
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Opioid Toxicity
Overdose
1. Miosis
2. Comatose state (A coma, or comatose is a deep state of
unconsciousness)
3. Respiratory depression
– Treatment:
• IV administration of naloxone
• Ventilatory support and other therapeutic measures
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Physical Dependency
• Physical dependence refers to a state in which
withdrawal of the drug causes adverse physiological
effects
Tolerance
• With frequently repeated therapeutic doses of opioids there is a
gradual loss in effectiveness; this loss of effectiveness is
denoted tolerance.
• Tolerance; is an increase in the dose needed to produce a given
pharmacological effect. Tolerance develops within 12-48 hrs
or few days.
• Drug rotation (changing from one opioid to another) is used to
avoid tolerance. 18
General notes
• Opioids cross the placenta and therefore should be used
with care during pregnancy and delivery because they
cause prolongation of labor and respiratory depression in
newborn.
• Morphine is contraindicated in head trauma because of the
risk of a rise in intracranial pressure from vasodilation, and
in acute asthma patients.
• Meperidine (pethidine) has less effect on uterine smooth
muscle so used in obstetrics.
• Other opioids include a drug called tramadol; a weak
agonist to μ receptor used for moderate to severe pain 19
Opioid Antagonists
Naloxane, Naltrexone and nalmefene:
Therapeutic uses:
Is used to reverse the coma and respiratory depression of opioid
overdose.
* Naloxone has short onset 30 seconds after IV and short duration
60-100 min
* Nalmefene is parenteral with t1/2 of 8-10 hrs.
* Naltrexone has a longer duration of action and can be given
orally.
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