Opioids

Question 1

What are the three types of opioid receptors present?

Answer 1

mu, kappa and delta

*two subtypes: Mu-1 and Mu-2 , three kappa receptor subtypes

Question 2

How are opioids classified?

Answer 2

Via their actions at the opioid receptors:

1) Pure agonist: stimulates opioid receptors
2) Agonist/antagonist: blocks one type of opioid receptor while stimulating another
3) Partial agonist: binds to an opioid receptor but are less efficacious compared to pure agonist drugs
4) Pure antagonist: attach to opioid receptors but do not activate receptor (reversal agents)

Question 3

What are examples of pure agonist and what do they do?

Answer 3

Morphine, hydromorphone, oxymorphone, meperidine, methadone, Fentanyl

• greatest effect at the Mu receptor = pure mu agonist
• best option for prevention and treatment of surgical pain
• great at treating both visceral and somatic pain
• effects are cumulative

Side effects:

• vomiting (Morphine most likely to cause this)
• hypoventilation rare unless extremely high dose rates
• Hydromorphone has been associated with hyperthermia in cats
• morphine, butorphanol and buprenorphine can also cause hyperthermia
• Low dose sedative agents such as acepromazine or dexmedetomidine can help decrease clinic
• Can use butorphanol to cause partial reversal

Question 4

Morphine fun facts

Answer 4

Cats have a decrease ability to metabolise the active ingredient morphine-6-glucuronide through glucuronidation and therefore morphine is less effective for cats.

Morphine and meperidine releases histamine if administered IV rapidly

Question 5

Methadone

Answer 5

Acts as an NMDA receptor antagonist which is beneficial for the treatment and prevention of ‘wind up’ pain.

Question 6

What should meperidine and methadone not be given with and why?

Answer 6

Monoamine oxidase (MAOI) or tricyclic antidepressants. Meperidine and methadone are serotonin reuptake inhibitors and when combined with the above can cause serotonin toxicity which could be life-threatening.

Question 7

What is an example of Partial mu agonist and what does it do?

Answer 7

Buprenorphine has a slow onset of action with peak effect occurring approximately 30-45 mins after IV or IM administration. Duration of action is dose dependent. Should only be used for mild to moderate pain as it has a ceiling effect.
Can inhibit a pure mu agonist from binding to the mu receptor due to its high affinity for the mu receptors. Problem if more analgesia is needed.

Question 8

Agonist and antagonist examples and what are they effective for?

Answer 8

Butorphanol and Nalbuphine. They stimulate the kappa receptor and antagonizes the mu receptor. Effective at treating mild pain in small animals. Good at treating visceral pain but should not be used as the sole analgesic for somatic pain.

• mild sedation in dogs and may not be seen in cats
• combined with other drugs = profound sedation
• can be used as reversal agents for pure agonist to partially reverse respiratory depression and sedation while maintaining some analgesic effect.
• vomiting not usually seen
• ceiling effect
• butorphanol 4-5X as potent as morphine

Question 9

Opioid antagonist

Answer 9

• Naloxone and Nalmefene
• completely reverse the adverse cardiopulmonary, sedation and analgesic effects of opioid drugs
• to avoid adverse effects from reversal drugs, total dose should be diluted in saline and titrated IV slowly to effect over 5-10mins
• Naloxone: 1-2min IV onset and within 5mins IM, duration 30-60mins
• Buprenorphine may be difficult to reverse, therefore won’t get complete reversal
• Nalmefene: similar onset to Naloxone, but duration is twice as long (1-2hrs). 4X more potent than Naloxone