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OPIOID
ANALGESICS
&
ANTAGONISTS

By: Dr:JAWAD MUMTAZ

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 History of OPIOID ANALGESICS

NORCOTIC ANALGESICS

 The “OPIUM POPPY” is the source of

crude “OPIUM” from which
Serturner in 1803 isolated the pure
alkaloid Morphine - named after
Morpheus,
“The Greek God of dreams”.

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 Which drugs called OPIOID ANALGESICS ???

The drugs which:

 Obtained from opium,
 Semi – synthetic derivatives from opium,
 Synthetic surrogates,
 Opioid like drugs whose actions blocked by Naloxone.
 Endogenous opioid peptides (Endorphin.
Enkephalins, Dynorphins).

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 OPIOID ANALGESICS & ANTAGONISTS

 Natural opium alkaloids:

Morphine, Codeine, Thebane.
 Semi-synthetic opium derivatives: Hydrocodon,
Dihydrocodeine, Diacetylmorphine, Oxymorphine.

 Synthetic opium substitute:

Mepridine, Methadone, Pentazocine, Phenazocine.
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 Opium antagonists:
Naloxone, Naltrexone, Nalmefene.

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 OPIOID ANALGESICS & ANTAGONISTS

 Strong agonists: Morphine, Fantanyl, Mepridine,

Heroin, Methdone, Dufentanil.

 Moderate agonists: Codiene, Propoxyphene.

 Mixed agonists: Buprenorphine, Pentazocine.

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 Antagonists: Naloxone, Naltrexone, Nalmefene.

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 Pharmacokinetics of OPIOID ANALGESICS
 Most opioid well absorbed
when given by
subcutaneous, I/M, oral.
 Some opioids used by
nasal insufflations,
transdermal patches, lozenges (lollipops).
 Morphine has higher first-pass effect.
 All opioids bind to plasma proteins.
 Localized in brain, lungs, liver, kidney, spleen.
 In skeletal muscle is less concentration.
 Excreted by kidneys and bile .
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 Metabolism of OPIOID ANALGESICS

 Morphine: morphine-3-glucuronide (M3G) &

morphine-6-glucuronide (M6G).
 Hydromorphone: hydromorphone-3- glucuronide.
 Diacetyl morphine: monoacetyl-morphine &
morphine.
 Meperidine: meperidine & non-meperidine.
 Fantanyl: not metabolized to active metabolite.
 Codeine & Oxycodone: convert to greater potent
metabolites.
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 Mechanism Of Action OPIOID ANALGESICS

Morphine act on its receptors:

ų = Miyo, MOR: analgesia, euphoria, sedation, miosis,

respiratory depression, decreased GIT motility,
smooth muscle spasm, nausea, vomiting, feeding,
release of growth & prolactin hormone.
қ = Kappa,KOR: analgesia, sedation, miosis, diuresis.
δ = Delta, DOR: analgesia, release of growth hormone.
σ =Sigma, NOR: learning and memory.

They are present in CNS and other tissues.

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 Mechanism Of Action OPIOID ANALGESICS

 1). Opioid analgesics bind to specific receptors in the

brain, which are coupled to inhibitory–G protein
Inhibits adenylyl cyclase inhibit release of
excitatory neurotransmitter from nerves terminals
containing nociceptive (pain) stimuli.
 2). Open K+ channel to inhibit post-synaptic neurons.
 3). Close Ca++ channels on presynaptic neurons to
inhibit release of neurotransmitters from nociceptive
nerves terminals.

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 CNS effects of Morphine

a). Analgesia: Relieves superficial & visceral pain by:

 Raising the pain-threshold perception.
 Alter the response to pain.
 Blocks the impulse between thalamus and cortex .

b). Euphoria: Produces a sense of emotional well being

termed euphoria.

c). Sedation: Drowsiness and clouding of mentation are

frequent effects of morphine.
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 CNS effects of Morphine

d). Respiratory depression: morphine depresses the

respiratory center in medula, there fore sensitivity of
respiratory center to CO2 is reduced.

e). Cough Suppression: A well recognized action of

morphine. Suppression of cough center in medula,
causes accumulation of secretions, which leads to
airway obstruction and atelectasis.

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 CNS effects of Morphine

f). Miosis: Stimulation of Edinger Westphal nucleus,

causes Pin point pupil.

g). Truncal rigidity: Rapid high dose i/v, increases

tone of muscles of trunk.

h). Nausea & Vomiting: By stimulating

chemo-receptor trigger zone.

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 Peripheral effects of Morphine

a). CVS: Most opioids have no significant direct effect

on heart.
 Hypotension and bradycardia may occur.
 Mepridine is an exception and has anti-muscarinic
action can result in tachycardia.
 When respiratory depression occur, PCO2 rises,
then cerebral vasodilatation occur and
increases intracranial pressure.

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 Peripheral effects of Morphine

b). GIT: Constipation, due to decrease motility of

smooth muscle and increase tone.

c). Biliary tract: Contract smooth muscles results in

biliary colic.
 Sphincter of Oddi may constrict, resulting in reflux
of biliary and pancreatic secretions, causes
elevate plasma amylase and lipase levels.

d). Uterus: Decrease uterine tone causes prolong labor.

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 Peripheral effects of Morphine

e). Renal: Renal functions decreased, due to

decreased renal blood flow.
 Ų- Miyo receptor has anti-diuretic action.
 Enhences renal tubular sodium reabsorption,
 Increases bladder sphincter tone, causes urinary

retention.
 Worsen the ureteric calculus colic.

f). Neuro-endocrine: Stimulate the releases of ADH,

prolactin and growth hormones.
Inhibit release of LH, FSH, ACTH and cortisol.
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 Peripheral effects of Morphine

g). Pruritus: Due to CNS effect, releases histamine

produces flushing and warming of skin.
Causes sweating and itching.
Induces purities and urticaria.

h). Miscellaneous: Opioids modulate the immune

system by effects on lymphocyte
proliferation, antibody production and
chemotaxis.

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 Clinical Uses Of OPIOID ANALGESICS
 Analgesia:
 Severe and constant pain.
 Pain associated with cancer & other terminal illness.
 Obstructive labor.
 Acute severe pain of renal and biliary colic.
 Painful myocardial ischemia.

 Diarrhea.
 Antitussive (Cough),
 Acute pulmonary edema.
 Pre-anesthesic medication.

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 Side effects of Morphine
 Physiologic & Psychological Dependence.
 Severe respiratory depression.
 Dysphoria, Mental clouding.
 Allergic reaction (itching),
 Increased I/C pressure.
 Bronchoconstriction.
 Nausea, Vomiting.
 Urinary retention.
 Tolerance.

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 Contraindications of Morphine

 Head injury.
 Hypotension.
 Emphysemia.
 During delivary
 Bronchial asthma.
 Impaired hepatic or renal function.

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 Drug Interaction with Morphine
 Depressant action enhanced by
phenothiazines,
mono amino oxidase inhibitors,
tricyclic anti depressant.

 Analgesia enhanced by amphetamine.

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 HEROIN
 Produced by acetylation of morphine.
 Due to greater lipid solubility, cross blood brain barrier.
 So causes severe euphoria.
 Convert to morphine (in body).
 No accepted medical use.

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 CODIENE

 Less potent analgesic.

 Good anti- tussive.
 Rarely produce dependence.
 Less euphoria.
 Often used in combination with aspirin.

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 MEPRIDINE
 A synthetic Opioid, used for acute pain.
Actions:
 Respirator depression.
 I/V decrease peripheral resistance.
 Dilate cerebral vessels.
 Increase C.S.F.
 Contract smooth muscle.
 Impede GIT motility.
 Dilate pupil (like atropine).

Adverse effect: Tremors, Muscle twitching, convulsions.

 Severe hypotension, Pupil dilation.
 Mono amine oxidase inhibitor causes convulsions,
hyperthermia.
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 METHADONE
 Synthetic.
 Orally effected.
 Longer duration of action.
 Mainly act on ų- Miyo receptor.
 Has strong analgesic action.
 Also causes constipation.
 Used for withdrawal of heroin.
 Metabolized in liver.
 Excreted by urine.

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 FANTANYL
 80 time more analgesic potency.
 With droperidol produce dissociated anesthesia.

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 Mixed agonist - antagonist

Pentazocine:
 Agonist on қ –Kappa receptor.
 Week antagonist at u- Miyo receptors.
 For dysphoria act on σ- Sigma receptor.
 For analgesia act on spinal cord receptor.
 At high dose respiratory depression,
decrease activity of GIT.
Increase BP, tachycardia,
hallucination, night mares.

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 OPIOID Antagonists
NALOXONE , NALTREXONE, NALMEFENE

 Naloxone is a morphine derivative and is

competitive antagonist at all morphine receptors.
 Bind to opioid receptors but fail to activate them.
 Rapidly reverse the effects of agonist (heroin).
 No effect in normal individual.
 Duration of action is 1-2 hours.

 Naltrexone has similar action but longer than

nalaxone.
 Nalmefene is derivative of naltraxone.
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