Summary of "Morphine 1"

Morphine Pharmacology Lecture Summary

This detailed lecture explores the pharmacology of morphine, covering its pharmacokinetics, pharmacodynamics, clinical effects, side effects, and essential clinical considerations. It is especially useful for medical students preparing for exams.

Main Plot & Highlights

Introduction & Pharmacokinetics

Morphine is described as the “godfather” of narcotic analgesics.
Oral morphine undergoes a significant first-pass effect, with about 70% metabolized by the liver, leaving only 30% bioavailable.
Alternative administration routes such as lozenges (buccal absorption), nasal inhalation, and injections bypass the first-pass metabolism.
Intramuscular (IM) or subcutaneous (SC) morphine should be avoided in shock due to poor peripheral circulation, which risks drug accumulation and toxicity.

Distribution

Morphine is lipophilic and crosses the blood-brain barrier.
It crosses the placenta, potentially causing congenital malformations and neonatal withdrawal syndrome in addicted pregnant women.
Use during labor can depress the newborn’s respiratory center, preventing the vital “cry of life.”
Naloxone (Nalogen) is introduced as an antidote; it can be administered to the mother before cord cutting or directly to the newborn.

Metabolism

Morphine is conjugated with glucuronic acid, producing two metabolites:
- Morphine-3-glucuronide (neuroexcitatory)
- Morphine-6-glucuronide (more potent analgesic than morphine)
Impaired liver function (in children or adults) increases morphine’s effects due to reduced metabolism.

Excretion

Morphine and its metabolites are mainly excreted via urine and gastric juice (about 20% in gastric juice).
This explains why gastric lavage is performed even if morphine was administered parenterally in overdose cases.

Mechanism of Action

Morphine acts on opioid receptors (mu, kappa, delta), which are G-protein coupled (Gi).
Effects include:
- Inhibition of adenylate cyclase
- Closing presynaptic calcium channels (reducing neurotransmitter release)
- Opening postsynaptic potassium channels (causing hyperpolarization)
Morphine also releases histamine, causing vasodilation, hypotension, skin redness, itching, and bronchospasm.

Central Nervous System (CNS) Effects

Inhibits:
- Cortex, thalamus, spinal cord (analgesia)
- Cough center (antitussive effect)
- Respiratory center (risk of respiratory depression)
- Heat regulator (causing hypothermia)
- Vasomotor center (vasodilation)
Inhibits sympathetic nervous system and activates parasympathetic nervous system, contributing to:
- Hypotension
- Bradycardia via stimulation of the cardiac inhibitory center (CIC)
Activates the chemoreceptor trigger zone (CTZ), causing nausea and vomiting—a serious risk during anesthesia due to aspiration.

Eye Effects

Causes miosis (pinpoint pupils) by activating the Edinger-Westphal nucleus in the brainstem, stimulating parasympathetic nerves to the eye.
Miosis is a classic sign of opioid use.
Eye drops of morphine do not cause miosis; systemic absorption is required.
Miosis can be reversed with naloxone, ganglion blockers, or atropine.

Reflexes

Morphine inhibits most reflexes except the monosynaptic stretch reflex, which it stimulates, leading to hyperreflexia.

Gastrointestinal Effects

Causes spasmogenic constipation by:
- Stimulating circular muscles (increasing segmentation)
- Inhibiting longitudinal muscles (reducing propulsion)
Causes sphincter spasms, blocking defecation reflexes, leading to severe constipation.
In biliary colic and renal colic, morphine alone is contraindicated because it causes spasm of the bile duct and ureteral sphincters, increasing pressure and risk of rupture.
Co-administration of atropine (a spasmolytic) is necessary to counteract these effects.

Endocrine Effects

Suppresses pituitary hormones (FSH, LH, ACTH, TSH), potentially causing:
- Gonadal dysfunction
- Adrenal insufficiency (Addison’s disease)
- Hypothyroidism (myxedema)
Increases antidiuretic hormone (ADH), causing oliguria.

Tolerance & Addiction

Initially causes euphoria and CNS excitation.
Tolerance develops within 10–14 days, reducing euphoric effects.
Tolerance does not develop for miosis and constipation, which persist.
Cross-tolerance with anesthetics means addicts require higher doses of anesthetics.

Notable Jokes & Teaching Style

The instructor uses humor and relatable examples, such as police officers checking eyes for narcotic use or the analogy of “throwing money on the ground” when morphine is given in shock but not absorbed.
The lecture is conversational, often addressing the viewer directly (“my dear friend,” “Ad”) and encouraging note-taking and memorization for exams.
Key points are frequently repeated, especially those important for multiple-choice questions (MCQs).
Visual aids and diagrams are recommended for complex topics like eye effects and reflexes.

Key Reactions & Clinical Pearls

Morphine in shock: Avoid IM or SC injections due to poor circulation and risk of sudden toxicity when circulation returns.
Pregnancy: Morphine causes birth defects and neonatal withdrawal; naloxone can reverse respiratory depression if given timely.
Morphine-induced hypotension: Multifactorial—histamine release, vasomotor inhibition, sympathetic inhibition, parasympathetic activation, and direct vasodilation.
Morphine and biliary/renal colic: Contraindicated alone; must combine with atropine to prevent sphincter spasms and increased pressure.
Morphine poisoning: Respiratory center depression is the main cause of death; naloxone is the antidote.
Tolerance: Develops to euphoric effects but not to miosis or constipation.

Personalities in the Video

The Lecturer/Doctor: The main speaker provides a comprehensive, detailed, and engaging explanation of morphine pharmacology with humor and interactive questioning.

This lecture stands out for its thoroughness, exam-focused approach, practical clinical advice, and memorable teaching style, making complex pharmacological concepts accessible and relevant for medical students.