UPSC MainsMEDICAL-SCIENCE-PAPER-I201415 Marks
Q21.

Write the mechanism of analgesic effect of morphine. Mention the adverse reactions of morphine and the antidotal treatment in its poisoning.

How to Approach

This question requires a detailed understanding of morphine's pharmacology, its adverse effects, and management of its overdose. The answer should be structured into three parts: mechanism of analgesic action, adverse reactions categorized for clarity, and antidotal treatment with specific drugs and their mechanisms. Focus on receptor types, pathways involved, and clinical manifestations of toxicity. A concise and systematic approach is crucial for a high-scoring answer.

Model Answer

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Introduction

Morphine, an opioid analgesic derived from the opium poppy, remains a cornerstone in the management of moderate to severe pain. Its potent analgesic properties stem from its interaction with the opioid receptor system within the central nervous system. However, its use is associated with a range of adverse effects, including respiratory depression and addiction, necessitating a thorough understanding of its pharmacology and the principles of managing its toxicity. This answer will detail the mechanism of morphine’s analgesic effect, enumerate its adverse reactions, and outline the antidotal treatment for morphine poisoning.

Mechanism of Analgesic Effect of Morphine

Morphine exerts its analgesic effect primarily through its interaction with three main opioid receptor subtypes: mu (µ), kappa (κ), and delta (δ). The µ-opioid receptor is most crucial for analgesia.

  • Receptor Binding: Morphine binds to µ-opioid receptors located in the brain (periaqueductal gray, thalamus, cortex) and spinal cord (dorsal horn).
  • G-protein Coupled Receptor Activation: These receptors are G-protein coupled receptors. Upon activation, they inhibit adenylyl cyclase, reducing cAMP levels.
  • Ion Channel Modulation: This leads to increased potassium conductance and decreased calcium conductance.
  • Reduced Neuronal Excitability: The net effect is hyperpolarization of the neuron, reducing its excitability and inhibiting the transmission of pain signals.
  • Descending Pain Pathway Activation: Morphine also activates descending inhibitory pathways originating in the brainstem, further suppressing pain transmission in the spinal cord.
  • Supraspinal Effects: Morphine produces analgesia by altering the perception of pain, reducing anxiety and distress associated with pain.

Adverse Reactions of Morphine

Morphine’s adverse effects are numerous and can be categorized as follows:

Category Adverse Effects
Central Nervous System Sedation, drowsiness, confusion, euphoria, dysphoria, hallucinations, respiratory depression (most serious), seizures (rare)
Gastrointestinal Constipation (very common), nausea, vomiting, abdominal cramping
Cardiovascular Bradycardia, hypotension, QT prolongation
Other Pupillary constriction (miosis), urinary retention, itching (pruritus), sweating, allergic reactions, endocrine disturbances (decreased cortisol, testosterone)

Antidotal Treatment in Morphine Poisoning

The primary antidote for morphine poisoning is naloxone, a competitive opioid receptor antagonist.

  • Mechanism of Action: Naloxone has a higher affinity for opioid receptors than morphine, displacing morphine and reversing its effects.
  • Administration: Naloxone is typically administered intravenously, intramuscularly, or intranasally.
  • Dosage: Initial dose is typically 0.4-2 mg IV, repeated every 2-3 minutes as needed, titrated to effect (respiratory rate >12 breaths/min, improved mental status).
  • Monitoring: Continuous monitoring of vital signs (respiratory rate, heart rate, blood pressure) is crucial.
  • Supportive Care: Supportive care includes airway management (intubation and mechanical ventilation if necessary), oxygen therapy, and fluid resuscitation.
  • Considerations: Naloxone’s duration of action is shorter than morphine’s, so repeated doses may be required until the effects of morphine wear off. Precipitation of withdrawal symptoms in opioid-dependent individuals is a potential complication.

Activated charcoal may be considered if the ingestion was recent (within 1 hour) and the patient is alert and able to protect their airway.

Conclusion

Morphine remains a valuable analgesic, but its use necessitates a comprehensive understanding of its mechanism of action, potential adverse effects, and the principles of managing its toxicity. Naloxone is the cornerstone of treatment for morphine overdose, but supportive care and careful monitoring are equally important. Ongoing research focuses on developing novel analgesics with reduced side effect profiles and lower addiction potential, aiming to improve pain management while minimizing the risks associated with opioid use.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Opioid Receptor Agonist
A substance that binds to and activates opioid receptors, producing effects similar to those of endogenous opioids (e.g., endorphins).
Naloxone
A synthetic opioid antagonist used to reverse the effects of opioid overdose, primarily by blocking opioid receptors in the brain.

Key Statistics

According to the CDC, over 106,000 drug overdose deaths occurred in the United States in 2022, with opioids being involved in nearly 73% of these deaths.

Source: CDC, National Center for Health Statistics (2023)

A study published in the New England Journal of Medicine in 2018 showed that naloxone distribution programs significantly reduced opioid overdose deaths in communities where they were implemented.

Source: New England Journal of Medicine, 2018

Examples

Post-Operative Pain Management

Morphine is frequently used for post-operative pain management following major surgeries, such as hip or knee replacements, due to its potent analgesic effects. However, careful monitoring for respiratory depression and constipation is essential.

Frequently Asked Questions

What is the difference between tolerance and dependence?

Tolerance is a physiological adaptation to a drug, requiring higher doses to achieve the same effect. Dependence is a state of physiological or psychological need for the drug to avoid withdrawal symptoms.

Topics Covered

PharmacologyPain ManagementOpioidsAnalgesicsDrug Toxicity