Paper I
2022 February (2019 Scheme) · 100 marks · 180 min

Question

Classify Opioid analgesics. Write the pharmacological effects, therapeutic uses, adverse effects and contraindications of Morphine. (4+3+3+3+2)

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Answer

Classification of opioid analgesics

BasisClassExamples
SourceNaturalMorphine, Codeine
SemisyntheticDiacetylmorphine (heroin), Pholcodine, Buprenorphine
SyntheticPethidine, Fentanyl, Methadone, Tramadol, Loperamide
Receptor actionPure agonistMorphine, Fentanyl, Pethidine, Codeine
Partial agonistBuprenorphine
Agonist-antagonistPentazocine, Nalbuphine (kappa agonist/mu antagonist)
Pure antagonistNaloxone, Naltrexone (no analgesic action — reverses overdose/dependence)
Potency/clinical useStrong agonistMorphine, Fentanyl
ModerateCodeine, Tramadol (mild-moderate pain, antitussive)

Pharmacological effects of Morphine Acts predominantly on mu (μ) receptors: mu-receptor bindingGi-protein coupling↓cAMPneuronal hyperpolarization → reduced neurotransmitter release and pain-signal transmission.

  • CNS: analgesia (raises pain threshold and alters perception — most effective against dull, continuous visceral pain)
    • Sedation and euphoria (dysphoria in some individuals)
    • Miosis — pinpoint pupils via Edinger-Westphal nucleus stimulation, a valuable diagnostic sign
    • Respiratory depression — reduced brainstem sensitivity to CO₂, the most dangerous acute effect
    • Antitussive action (cough-centre suppression)
    • Nausea and vomiting (direct chemoreceptor trigger zone stimulation)
  • GIT: markedly reduced motility and increased sphincter tone — constipation, risk of biliary/sphincter of Oddi spasm
  • CVS: minimal effect supine; postural hypotension and bradycardia can occur, partly via histamine release
  • Other: histamine release (itching, urticaria, bronchospasm in susceptible individuals); ADH release (reduced urine output)

Therapeutic uses

  • Severe acute pain — post-operative, myocardial infarction (also relieves associated anxiety and reduces sympathetic-driven cardiac work)
  • Chronic cancer pain — WHO analgesic ladder, step 3
  • Acute left ventricular failure/pulmonary edema — reduces preload via venodilation, relieves air hunger
  • Pre-anesthetic medication
  • Obstetric analgesia (used cautiously — crosses the placenta)
  • Cough suppression and diarrhoea control, via congeners such as codeine and diphenoxylate

Adverse effects

  • Respiratory depression — dose-related, the most serious acute toxicity
  • Constipation — no tolerance develops to this effect, unlike most others
  • Nausea and vomiting
  • Sedation and mental clouding
  • Miosis
  • Urinary retention
  • Tolerance and physical/psychological dependence with chronic use
  • Histamine-mediated hypotension, flushing, and pruritus

Contraindications

  • Head injury/raised intracranial pressure — CO₂ retention from respiratory depression further raises ICP, and miosis masks the pupillary sign of deterioration
  • Bronchial asthma — histamine-mediated bronchospasm
  • Severe hepatic impairment — reduced first-pass metabolism, risk of toxicity
  • Labour and near-term pregnancy — neonatal respiratory depression
  • Concurrent MAO inhibitors — risk of a serotonin-syndrome-like reaction, particularly with pethidine

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