Opioid Analgesics (save pharmaco)

Question 1

What do phenanthrenes include?

Answer 1

• Morphine and codeine

- Morphine forms a significantly larger bulk of phenanthrenes than codeine, and is a much stronger opioid agonist.

Question 2

Functional effects of mu, delta and kappa receptors

Answer 2

• Three receptors: mu, delta and kappa
• Kappa is the only receptor that causes dysphoria
• Mu and delta both cause euphoria, but mu causes more of it.
• Mu receptor is the only receptor that responds to supra spinal (brain) analgesia
• Mu receptor is responsible for a lot of functional effects.
• It is unknown if delta receptor has any effect on spinal analgesia.

Question 3

Dosing features of opioid analgesics

Answer 3

• Elderly patients require a lower dose to achieve effective pain relief than younger ones.
• Neuropathic pain requires higher opioid doses than nociceptive ones
• Lower doses are used for continuous maintenance of pain relief, than administration in response to recurrence of pain

Question 4

Dosing to effect opioid analgesics

Answer 4

• Opioid doses should be carefully titrated upwards until a minimum dose is reached, or when side effects prove so unacceptable that a re-evaluation of therapy is required.
• Failure of at least partial analgesia with incremental dosing in patient that is on opioid therapy for the first time —> patient’s pain syndrome may not be responsive to opioids
• For some patients with chronic pain, patients’ opioid levels need to reach a therapeutic threshold for there to be effects.

Question 5

What are the clinical uses of opioid agonists?

Answer 5

Pethidine: analgesia
Codeine: analgesia, antitussive/cough suppressant
Diphenoxylate: antidiarrhoeal

Question 6

Pethidine (meriperidine)

Answer 6

• Strong mu agonist (weaker delta and kappa agonist)
• Shorter duration of action than morphine (especially for neonates, therefore used in labour)
• N-demethylated in the liver to norpethidine (hallucinogenic and convulsant effects at high dose)
• Restlessness rather than sedation
• Antimuscarinic effects (dry mouth), lack of meiosis (dry eyes) and less spasm of smooth muscle

Question 7

Codeine

Answer 7

• Weak mu and delta agonist (not a kappa agonist)
• Low maximum analgesic efficacy (effective for analgesia)
• Moderate liability for addiction/abuse.
• About 10% converted to morphine and its derivatives
• ~10% of population show reduced analgesic effect due to lack of demethylating enzyme

Question 8

Adverse effects of opioid dosing

Answer 8

- respiratory depression 
>> occurs in the nucleus tractus solitarius and nucleus accumbens 
>> reduce response to H+ and CO2 
>> suppress voluntary breathing 
- nausea/vomiting 
- constipation 
- drowsiness 
- suppressed immune system 
- postural hypotension and bradycardia 
- miosis (pinpoint pupil) 
- urinary retention

Question 9

Effects of morphine triggering histamine release

Answer 9

• Urticaria and itching
  
  • Bronchoconstriction
  • Hypotension due to vasodilatation

Question 10

What group of people is morphine not suited for?

Answer 10

• those with asthma

Question 11

What medications should be prescribed in the event of opioid overdose.

Answer 11

• opioid antagonists like naloxone (short-acting, IV)

- must use with extreme care in patients with opioid dependency as it can lead to fatal withdrawal syndrome.