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Opioid Analgesics
• Analgesics: Are the Drugs which selectively
relieves pain by acting in the CNS or on
peripheral pain mechanisms, without
significantly altering the consciousness –
Opioids and NSAIDS
• Narcotics Those drugs which possess both
an analgesic (pain relieving) and sedative
properties.
• Opioids include natural and semisynthetic
alkaloid derivatives from opium, as well as all
other compounds whose opioid like actions
are blocked by the nonselective opioid
receptor antagonists (Naloxone).
Poppy Plant - image
• Pain: Is unpleasant sensory and emotional
experience associated with actual or potential
tissue damage.
• Nature of Pain Cannot be objectively
measured Certain types of pain produce
predictable symptoms Pain Assessment-nurse
relies on clients words and behaviors changes
behavior
Types of pain…
• a) Somatic Pain:
• Arises from bone, joint,
muscle, skin or connective
tissue Usually aching,
throbbing, well-localized
pain. Responds to traditional
analgesia
b) Visceral Pain:
Arises from visceral organs
such as the GI tract,
heart, and pancreas.
often described as having a burning or electrical
quality. It may feel like a shock. The other major classes
of medications useful for neuropathic pain are tricyclic
antidepressants, anticonvulsants
•
Classification of Pain
By
Onset
and
Duration
Acute pain
– Sudden in onset
– Usually subsides once treated
• Chronic pain
– Persistent or recurring
– Often difficult to treat
Opioid Peptides
• Opioids include several endogenous peptides
that are synthesized by nerve cells and adrenal
medullary cells and interact with opioid
receptors
• Endogenous peptides that act on opioid
receptors as endorphines, dynorphines and
enkephalines.
• µ, δ , K and σ are different types of opioid
receptors.
• Endogenous opioid peptides have been
implicated in pain modulation.
• They can be released during stressful
conditions such as pain or the anticipation of
pain.
Classification of OPIOIDS
• Natural
• morphine
• codeine
• thebaine
• semisynthetic
– heroin
• synthetic
– meperidine
– methadone
– Dextromethorphan
– Fentanyl
– pentazocin.
•
Classification
• Strong agonists
E.g.: Morphine, Methadone.
• Moderate agonists.
E.g.: Codeine
• Mixed agonist-antagonist
E.g.: Pentazocine
• Antagonists.
E.g.: Naloxone
Morphine
• MOA : Morphine and other opioids act
through binding to opioid receptors.
• These receptors distributed in the CNS at
regions involved in transmission and
modulation of pain.
Pharmacological Actions
• Strong agonist:
• Acute effects:
1. Analgesia: changes both pain perception and
reaction to pain.
•
•
•
Visceral pain is relieved better than somatic
pain
Degree of analgesia increases with dose
Nociceptive pain is better relieved than
Neuropathic pain
Pharmacological Actions
2.Euphoria: Morphine produces a powerful
sense of contentment and well-being
3. Sedation, drowsiness and hypnosis.
Additive with other CNS depressants.
Pharmacological Actions
4.Respiratorydepression: Inhibits respiratory
center and decreasing its sensitivity to CO2.
– The respiratory depression is dose-related.
• Death from morphine overdose is usually due
to respiratory failure
Pharmacological Actions
5.Antitussive:Opioids suppress the cough reflex
Produced by depression of neurons in medulla
which control the cough reflex
• Codeine is a potent inhibitor of the cough reflex
• Meperidine has a weak effect
Pharmacological Actions
6.Miosis:Opioids act on  and  receptors to
stimulate oculomotor nucleus to constrict
pupil. Pin point pupils are characteristics of
morphine overdose.
Pinpoint pupil
Pharmacological Actions
7. Nausea and vomiting: Stimulation of CTZ.
8. GIT effects – Decreases GI motility
Increases GI tone,Produces constipation .
9. Urinary retention: Due to contraction of
sphincter, inhibition of reflex of urination and
increase ADH.
Pharmacological Actions
10. Biliary tract: Contraction of biliary muscle and
sphincter of Odi  Biliary tract spasm
Opioids can exacerbate biliary colic
11. Uterus: Decreases tone and prolong labor.
12. sedation& have anxiolytic effects
Pharmacological Actions
13. CARIOVASCULAR SYSTEM
• No prominent effects
• Peripheral vasodilation most prominent
effect due to histamine release and
decreased adrenergic tone
• Very high doses may produce bradycardia
• Because of respiratory depression and carbon
dioxide retention, cerebral vessels dilate and
increase the cerebrospinal fluid (CSF) pressure.
Therefore, morphine is usually contraindicated in
individuals with severe brain injury.
14. Histamine release: Morphine releases histamine
from mast cells, causing urticaria, sweating, and
vasodilation. Because it can cause
bronchoconstriction, asthmatics should not receive
the drug.
• Chronic effects:
1. Tolerence:
• Tolerance and physical dependence are
manifestations of chronic use
2. Dependence
Psychological “Craving”.
• Physical or physiological, sudden Abnormal
physical state in which the drug must be
administered to maintain “normal” function.
• Physical dependence is manifested by
“withdrawal symptoms” when administration
of the drug is stopped.
• Physical dependence is a powerful
reinforcement for continued drug taking
behavior
Therapeutic uses of Morphine
1. Analgesic – postoperative pain
Cancer pain.
Renal colic.
2. Acute pulmonary edema (LVF). To decrease
anxiety and pre and after loads.
3. Antitussive in severe and refractory cough.
codeine has greater antitussive effect than
morphine.
Therapeutic uses of Morphine
4. Preanesthetic medication.
5. treatment of diarrhea????
Contraindications
• Contraindications and cautions in therapy:
Use of pure agonists with weak partial agonists.
Use in patients with acute head injuries.
may increase the risk of hemorrhage - respiratory
depressant effect increases PCO2  cerebral
VD and also morphine can increase the ICP
Use during pregnancy.
Fetal respiratory depression and withdrawal
syndrome.
 Impaired renal and hepatic functions.
 Bronchial asthma and chronic respiratory
diseases. Due to : Respiratory center
depression , bronchoconstriction and
histamine release.
OTHER OPIOIDS
Meperidine –
• less potent than morphine
• high doses produce excitation and convulsions
• less smooth muscle spasm and miosis,less
respiratory depressant effects. little antitussive
action than morphine
• Uses:
• Analgesic as substitute of Morphine
• Preanaesthetic medication
• As analgesic during labor – less fetal
respiratory depression
Heroin
not used clinically highly addictive.
Methadone: Oral less addictive than morphine,
with no or mild withdrawal syndrome.
Therapeutic uses: Methadone is used as an
analgesic as well as in the controlled
withdrawal of dependent abusers from heroin
and morphine.
Moderate agonist
Codeine –
• less potent than morphine
• mainly used as antitussive
• Mixed agonist – antagonist and partial
agonist.
• Drugs that stimulate one receptor but block
another are termed mixed agonist-antagonists
Pentazocin - Κ - agonist and weak µ
antagonist or partial agonist.
• ANTAGONISTS
• Naloxone –
• Readily reverses the coma and respiratory
depression of opioid overdose.
• Within 30 seconds of IV injection of naloxone,
the respiratory depression and coma
characteristic of high doses of heroin are
reversed
Clinical Uses
•
•
•
•
•
•
Analgesia- Fentanyl, morphine
Cough Supression- Codeine, Dextromethorphan.
Antidiarrheal- Diphenoxylate, Loperamide
Acute Pulmonary edema- Morphine
Anesthesia- Fentanyl
Opioid Dependence- Methadone
Tramadol
• Tramadol is a strong analgesic which blocks
serotonin reuptake.
• It is a weak µ receptor agonist, so can be used
with full agonists for chronic neuropathic pain.
• It induces seizures and is relatively
contraindicated in patients with a history of
epilepsy.
QUESTIONS
•
•
•
•
•
•
Match each of the descriptions below with the appropriate drug
(A) Loperamide
(B) Codeine
(C) Naloxone
(D) Methadone
(E) Dextromethorphan
• 1. Weak–to-moderate opioid agonist with a higher ratio of oral to
parenteral activity than morphine
• 2. Antitussive with no dependence liability
• 3. Opioid-receptor anatgonist
• 4. Strong opioid agonist that has a longer duration of action and
produces less intense withdrawal syndrome than morphine