Opioids

Question 1

Contrast weak vs strong opioids

Answer 1

• difference in duration of action and potency
• weak opioids have ‘ceiling effect’ - at some point no matter how much you increase the dose, you will not increase the analgesia

Question 2

Name some strong opioids

Answer 2

• morphine (0.1/0.3 mg/kg)
• oxycodone
• diamorphine
• fentanyl (1-2mg/kg)
• pethidine
• remifentanil
• methadone

Question 3

Name some weak opioids

Answer 3

• codeine
• tramadol
• dihydrocodeine
• loperamide (not analgesic, used to treat diarrhoea)

Question 4

What are the opioid antagonists?

Answer 4

• naloxone

* naltrexone

Question 5

How are opioids absorbed in the body?

Answer 5

• most opioids are weak bases
• unionised form more diffusable (as it can pass membranes)
• absorbed in more basic (alkaline) environment in small intestines for first pass metabolism through the portal vein to the liver
• act on opioid receptors (mu opioid peptide receptors (MOP)) located in dorsal horn and spinal cord for analgesic effects

Question 6

What are the opioid receptors?

Answer 6

• mu opioid peptide receptor (MOP)
• kappa (KOP)
• delta (DOP)
• nociception (NOP)

Question 7

Describe the mechanism of opioids at the cellular level

Answer 7

• opioid receptor = 7 transmembrane G-coupled protein receptor
• activation leads to intracellular inhibition of transduction pathways
• results in stimulation of K+, inhibition of adenylate cyclase causing NT release, and inhibit voltage-gated Ca2+ channels

Question 8

Describe the action of opioids on the body

Answer 8

CNS:

• euphoria (risk of misuse and dependence)
• analgesia
• sedation (good/bad)
• miosis (from MOP receptors in Edinger-Westphal nucleus), resp depression and decreased tidal volume (overdose)

Resp:

• can be anti-tussive (good in lung cancer) eg. codeine linctus
• can cause bronchoconstriction (asthma caused by histamine release)

CVS:
* bradycardia due to decreased sympathetic drive (via SA node) and peripheral vasodilation (decreased BP)

GI:
* constipation (give laxative) and nausea (give anti-emetic) due to delayed motility

General:

• itch
• urinary retention
• immune suppression (NK cells)
• decreased ACTH and prolactin
• increased ADH

Question 9

Describe the metabolism of opioids

Answer 9

Most are prodrugs - metabolised by cytochrome system in liver to release active drug