Opioid Analgesics

Question 1

What are the major analgesic drug classes?

What are Opiates? Give an example

What are Opioids?

What type of receptors do Opioids act at?

Which type of opioid receptors are associated with Morphine and analgesia?

Answer 1

• Major Analgesic drugs - Opioids, NSAIDs, TCAs, Anticonvulsants, CCBs, Cannabinoids
• From Poppy somniferum e.g. Morphine, Codeine
• Endogenous (e.g. Endorphin) and Synthetic (e.g. Fentanyl) compounds that produce morphine-like effects
• GPCRs; linked to Gi/Go
• MOP receptors

Question 2

What do opioids do to synaptic transmission?

How do opioids affect synaptic transmission at the pre-synaptic and post-synaptic membranes?

What do opioids do to descending inhibition? Where does it act to do this?

How does it do this?

Where are opioid receptors found?

What does it do to the Nociceptive inputs?

Answer 2

• Reduce it
• • Presynaptic; binds to ↓VGCC/Ca2+ influx, ↑VGK/K+ efflux = Hyperpolarisation = ↓NT release
  • Postsynaptic; binds to ↑VGKC/K+ efflux = Hyperpolarisation = ↓AP firing
• Increases Descending Inhibition; act within the Periaqueductal Grey Matter of the brainstem
• Opioids switch off Inhibitory interneurons in P. Grey Matter by decreasing inhibition of the inhibitory pathway = Disinhibition
• Found at major sites of the Nociceptive pathways; In Periphery, Dorsal Root Ganglion, Dorsal Horn, and Descending Inhibitory Pathway (brainstem)
• ↓Nociceptive inputs (weaker effect)

Question 3

What type of substance are opioids? Where are they absorbed?

Why are they mainly given IV/IM?

What are the pro-drugs to morphine?

Where is morphine broken down? What are the 2 metabolites produced?

When is it important to carefully monitor opioid (in terms of its excretion)?

Answer 3

• Weak bases (unionised); absorbed in intestines
• Significant first-pass metabolism = Poor bioavailability
• Codeine, Methadone, Diamorphine (Heroin)
• Liver into Morphine-3-Glucoronide (inactive) and Morphine-6-Glucoronide (active)
• With kidney failure; will cause opioid buildup

Question 4

What is Diamorphine?

What is Buprenorphine? What is it used to treat?

What is Naloxone? What is it used to treat?

What are the common signs of an Overdose?

Answer 4

• Heroin; Full agonist
• Partial Agonist; Long duration, Treatment for Heroin Addiction
  o Won’t produce as much of a response as heroin; useful for withdrawal
• Naloxone is a Competitive Antagonist; Non-specific
  o Reverses morphine-induced symptoms, Used to reverse overdose problems
• Pupil constriction, Coma, Respiratory depression

Question 5

What are the Side-effects of Opioid use?

How do opioids cause Euphoria?

How do opioids cause Respiratory depression?

How do opioids cause Vomiting?

How do opioids cause Pupil constriction? Why is it important for diagnosing overdose?

How do opioids cause Constipation?

How does Histamine release from opioid use affect the body?
→ In which condition are opioids avoided, and why?

Answer 5

• Euphoria, Respiratory depression, Vomiting, Pupil constriction, Constipation, Histamine release, Suppression of cough reflex
• Relieves stress, making it an important ‘analgesic’ drug for anxious/distressed patients
  o Disinhibition of Dopamine release by inhibition of GABAnergic interneurons
• Opioid receptors in respiratory areas of brain (Pre-Botzinger Complex, Brainstem, Medullary Nuclei Chemoreceptors)
  o Suppression of respiratory pattern; chemoreceptors become less sensitive to pCO2, which is the driver of ventilation rate
• Stimulates Chemoreceptor Trigger Zone (Area Postrema) = Emesis
  o Morphine often given with Metoclopramide (Anti-emetic)
• Stimulates oculomotor nerve and ↑Parasympathetics = Pupil constriction
  o Important feature for diagnosing overdose; Other causes for loss of consciousness will cause pupil dilation instead of constriction
• ↑Tone, ↓Motility of GI = Constipation
• Inflammation, BRONCHOCONSTRICTION and Hypotension
  → ASTHMA due to the bronchoconstriction