L20

Question 1

opiate

Answer 1

• naturally occurring substances found in opium poppy (Papaver somniferum)
  o codeine
  o morphine (the Greek God of dreams, Morpheus)
• a long history of social and medicinal use

Question 2

opioid

Answer 2

• substances with an affinity for opioid receptors

Question 3

endorphins (endogenous morphine)

Answer 3

• methionine-enkephalin & leucine-enkephalin
• a common tyrosine residue (except nociceptin)

Question 4

Opioid receptors

Answer 4

*MOR / µ - cloned in 1993; primary drug target for opioids to induce analgesia
*KOR / [k] - cloned in 1993
*DOR / delta - cloned in 1992
* NOP - cloned in 1994, >60% amino acid sequence homology; nociceptin/orphanin FQ receptor

Question 5

All opioid receptors are what type of receptors

Answer 5

G-coupled protein
Associated with G-alpha(i)

Question 6

µ opioid receptors side-effect

Answer 6

• analgesia (good one)
• respiratory depression
• miosis (pupillary constriction)
• sedation
• reduced airway reflexes
• nausea and vomiting
• constipation
• dependence

Question 7

G-alpha (i)

Answer 7

Inhibit adenylate cyclase

Question 8

G-alpha (s)

Answer 8

Activate adenylate cyclase

Question 9

G-alpha (q)

Answer 9

Activate phospholipase C

Question 10

µ opioid receptor-mediated signalling all

Answer 10

1. G protein-dependent signalling (associated with analgesia) - activity of adenylate cyclase ↓, G protein-gated inwardly rectifying K+ channels (GIRK/Kir3) ↑, voltage-gated calcium channels ↓
2. G protein-independent signalling - the involvement of arrestin (a scaffold protein)
3. other signalling pathways - G protein-dependent or independent?

Question 11

µ opioid receptor-mediated signalling G-dep

Answer 11

• associated with analgesia
• activity of adenylate cyclase ↓,
• G protein-gated inwardly rectifying K+ channels (GIRK/Kir3) ↑,
• voltage-gated calcium channels ↓

Question 12

µ opioid receptor-mediated signalling G-indep

Answer 12

involvement of arrestin (a scaffold protein)

Question 13

µ opioid receptors and analgesia (locations)

Answer 13

• periphery
• Dorsal horn of spinal cord
• brainstem

Question 14

µ opioid receptors and analgesia (full)

Answer 14

• periphery - nociceptive fibres - reduce neuronal excitability
• Dorsal horn of spinal cord
  –presynaptic - ↓ release of substance P and CGRP
  – postsynaptic - ↓ neuronal excitability
• brainstem
  – stimulate the descending inhibitory pathway

Question 15

Typical opioids - codeine and morphine

Answer 15

• Codeine –CYP2D6–> morphine
• Codeine - prodrug
• go through CYP2D6 polymorphism
• Morphine –UGT2B7–> morphine-3 glucuronide (inact) and morphine-6-glucuronide (act)

Question 16

Metaboliser types:
copies of functional and/or defective genes
plasma concentration-time curve (shaded
area = therapeutic window)
response to a pharmacologically active
parent drug

Answer 16

Ultrarapid metaboliser (UM)
Extensive metaboliser (EM)
Intermediate metaboliser (IM)
Poor metaboliser (PM)

Question 17

Codeine effects

Answer 17

• good oral bioavailability
• mild to moderate acute pain
• analgesic effect required conversion to morphine
• cough suppressant
• nausea, vomiting and constipation

Question 18

Morphine effects

Answer 18

• predominantly a µ-receptor agonist
• treat moderate to severe acute pain
• used perioperatively (during anaesthesia and post-operative analgesia)
• minimise life-threatening adverse effects, e.g., respiratory depression
  o patients at risk of airway/breathing complications
• cautious use in hepatic and renal failure

Question 19

µ-receptor agonists

Answer 19

• morphine