The document is a seminar presentation on opioid analgesics, detailing their history, classification, mechanisms of action, pharmacological effects, and therapeutic uses. It elaborates on morphine as a potent opiate analgesic with various classifications of opioids, including agonists and antagonists, alongside their respective actions and side effects. Additionally, it discusses specific opioids like codeine, tramadol, fentanyl, and the role of endogenous opioid peptides.

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OPIOID ANALGESICS
A Seminar as a part of curricular requirement
for I year M. Pharm I semester
Presented by
B . Kranthi Kumar
(Reg. No. 20L81S0108)
Under the guidance/Mentorship of
Mr. A. Sudheer Kumar., M.Pharm, Ph.D.
Associate Professor
Dept. of Pharmacology

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• Terms
• History
• Classification
• Morphine
• Opioid receptors
• Mechanism of action
• Pharmacological actions of morphine
• Pharmacokinetics
• Adverse effects
• Contraindications
• Therapeutic uses
• References
CONTENTS

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• Algesia : Pain - warning signal that indicate some abnormality.
• Analgesia : The drugs designed to relieve pain without causing loss
of consciousness.
• Opioid analgesics : These are derived from crude extracts of papaver
somniferum (a poppy plant) act on CNS and produce morphine like
actions.
• Opiates : These are drugs derived from opium poppy plant.
TERMS

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• Sumerians used dries juice from the seeds of
opium poppy
4000 B.C
• Freidrich serturner, a German pharmacist, isolated
morphine, the major active alkaloid from opium resin.
1803
• Jean Robique isolated codeine from the resin.
1832
• Otto schumann synthesised the opiod drug, meperidine
1939
• Goldstein identified the polypeptide, endorphin in the
brain.
1975
• Solomon Snyder (JOHNS HOPKINS) identified the
opiate (enorphin) receptor sites in the limbic system of
brain.
1977
HISTORY

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CLASSIFICATIONS OF OPIOIDS
1. Opioid agonist
a)Natural opium alkaloids :
 Morphine
 Codeine
 Thebaine
 Papaverine
b) Semi synthetic opiates :
 Heroin
 Pholcodine
 Hydromorphone
 Oxymorphone
c) Synthetic opioids :
 Tramadol
 Methadone
 Fentanyl and Pethidine (Meperidine)

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2. Opioid against – antagonist : Pentazocine
Butorphanol
3.Partial µ-receptor agonist : Buprenorphine.
& k receptor antagonist
4. Opioid antagonist : Naloxone
Naltrexone
Nalmefene
5.Opioid peptides : Endorphins
Enkephalins
Dynorphins

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MORPHINE is a highly potent opiate analgesic
drug and is the most important alkaloid of opium.
It is the Prototype opiate.
Directly acts on CNS to relive pain.
Highly addictive when compared to other substances.
Produce action through – opioid receptors.
They also open k+ channel - Hyperpolarisation.
They also inhibit the opening of ca +2 channel-Depolarisation.
.
MORPHINE

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Type of receptor Location Effects
µ (Mu) •Brain stem
•Lymbic system
•Dorsal horn of spinal cord
•Sedation
•Analgesia
•Euphoria
•Respiratory depression
•Constipation
•Miosis
•Itching
K (Kappa) •Central cortex
•Hippocampus
•Mid brain
•Psychomimetic effects:
dysphoria
•Analgesia
δ (delta) •Brain
•Spinal cord
•Spinal analgesia
•Respiratory depression
Opioid Receptors

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MECHANISM OF ACTION

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Pharmocological actions of Morphine
Morphine has mainly CNS depressant effects but also has
stimulant effects at certain sites in the CNS.
1.CNS
a) Depressant effects :
I. Analgesic effect
II. Euphoria
III. Sedation
IV. Respiratory depression
V. Cough supression
VI. Hypothermia
b) Stimulant effects :
I. Miosis
II. Nausea and vomiting
III. Vagal centre

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2) CVS :
 Morphine produces vasodilation and fall of B.P
3)GIT :
Morphine causes constipation by direct action on GIT.
Decrease GIT motility and increase the tone of spinchters.
4)Urinary bladder :
It may cause urinary retention by incresing the tone of urethral
spinchter.
5)Histamine release :
Morphine is a Histamine liberator and causes itching, skin
rashes, utricaria

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PHARMACOKINETICS
Oral bioavailability of Morphine is poor.
So commonly administered by I.V, I.M (or) subcutaneous
routes.
It is widely distributed in the body, crosses placental barrier.
Metabolised in liver by glucuronide conjugation.
Morphine is excreted in urine.

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Adverse effects
1. Nausea & vomiting
2. Constipation
3. Respiratory depression
4. Hypotension
5. Drowsiness, confusion & mental clouding
6. Itching and skin rashes
7. Difficulty in micturition
8. Drug tolerance develops to most of the effects of morphine
9. Drug dependence (physical & psychological)
10. Acute Morphine poisoning

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Contraindications
• Head injury
• Bronchial asthma
• COPD
• Hypothyroidism
• Infants & Elderly
• Hypotensive states
• Undiagnosed acute abdominal pain
• Hepatic & renal diseases

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1. As analgesic
2. Pre- anaesthetic medication –opioids like morphine & pethedine
are used ½ hr before anaesthesia because of their sedative,
analgesic & euphoric effects the dose of anaesthetic required is
reduced.
3. Acute pulmonary oedema (cardiac Asthama) – I.V morphine
relieves breathlessness associated with acute left ventricular
failure due to pulmonary oedema.
4. Post anaesthetic shivering – pethedine is effective.
5. Cough – codeine used for suppression of dry cough
6. Diarrhoea – Loperamide and diphenoxylate are used for
symptomatic treatment of diarrhoea.
Therapeutic Uses

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Codeine
•Natural opium alkaloid
• Commonly used form of this drug is codeine sulphate.
• It has analgesic and cough supressant effects.(Anti tussive activity).
• In addition, it also causes sedation, constipation, drowsiness and
respiratory depression.
• The analgesic properties of codeine are arise from its conversion to
morphine.
• Cytochrome P4502D6 is the major enzyme responsible for conversion
of codeine to morphine.
• Compared to morphine
less potent
less respiratory depresent effect.

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Tramadol
 It is a synthetic µ receptor agonist.
 It is the 5-HT and NE reuptake inhibitor.
 It decreases seizure threshold.
• Pharmocological uses of Tramadol
o Analgesia
o Respiratory depression
o Nausea and vomiting
o Euphoria
o Constipation
o Sedation
o Physical and pschycological dependence

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Fentanyl
It is a synthetic opioid with a potent µ-agonist effect.
It is 100 times more potent than morphine as an analgesic.
Pharmacological actions are similar to morphine.
Pentazocine
 Opioid agonist-antagonist (mixed action).
It shows agonistic action at K receptor and weak antagonist
action at µ receptor.
 In low doses, PA and side effects are similar to morphine.
 In high doses, tachycardia, palpitations and rise in BP are seen.

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Buprenorphine
 It is a partial µ receptor agonist and K receptor antagonist.
 It is 25 times more potent than morphine as analgesic.
 Pharmological actions are similar to morphine but it has a
delayed onset and prolonged duration of action.
Opioid antagonist
Naloxone and Naltrexone
 These are pure opioid antagonist and have low agonistic activity.
 These drugs compititively reverse the effects of both natural and
synthethic opioid.

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Naloxone
 Orally not effective because of high first pass metabolisms.
 On I.V admistration , it immediately antagonists all the actions.
 I.V naloxone precipates withdraw symptoms in morphine and heroin
addicts.
Uses:
• It is mainly used for the treatment of morphine and other opioid
poisoning.
• In the treatment of opioid overdose, I.V naloxone rapidly reverses
respiratory depression induced by opioids (except Buprinorphine).
• To treat Neonatal asphyxia.

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Uses of Naltrexone
• It is orally more potent and has longer duration of action than
naloxone
• Naltrexone is used for opioid blockade therapy to prevent relapse in
opioid dependent individuals.
• It is also used for treatment of alcoholism as it reduces to urge the
drink.
• Methyl naltrexone, derivative of naltrexone used for the treatment of
constipation due to opioids.

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Endogenous opioid peptides
• Induce analgesia in humans and antinociception in animals.
• These are small molecules that are produced naturally in CNS and in
various glands.
• Serves as neuromodulators and act in brain and spinal cord.
Endorthins (Poly peptide)
• Natural painkiller.
• May also has a role in preventing obesity, diabetes, psychiatric
disorders.
• High affinity to µ-receptors.

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Enkephalin (pentapeptide)
• Also considerd as neuropeptides
• Found in brain and adrenal medulla.
• This can bind to δ and µ opioid and receptors.
Dynorphin
It is arise from the precussor protein prodynorphin.
Pro Protein convertase converts prodynorphin into dynorphin A
and dynorphin B.
Found In CNS, hypothalamus, midbrain, spinal cord.
Binds to K receptors.

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References
1. Goodman and Gillman‘s. Pharmacological Basis of
Therapeutics.
2. Katzung, B.G. Basic and Clinical Pharmacology.
3. Tripathi, KD. Essentials of Medical Pharmacology.
4. Craig Charles R. & Stitzel Robert E., Lippincott
Publishers. Modern Pharmacology with Clinical
Applications.

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