Opioids

Question 1

Opiates

Answer 1

Act on the opioid receptors
Mimic endogenous opioids
Examples: morphine, heroine and fentanyl

Question 2

Naloxone

Answer 2

µ, δ, κ antagonist
Used to treat overdose

Question 3

Central sites of endogenous analgesia

Answer 3

• Nociceptive neurons go to the spinal cord and are inhibited by opioid receptors.
• Signals in the spinal cord are also inhibited by opioid receptors
• Pleasant signals in the medulla are boosted by the action of opiates

Question 4

µ receptor and sites of analgesia

Answer 4

Supraspinal: +++
Spinal: ++
Peripheral: ++

Question 5

δ receptor and sites of analgesia

Answer 5

Supraspinal: -
Spinal: ++
Peripheral: -

Question 6

κ receptor and sites of analgesia

Answer 6

Supraspinal: -
Spinal: +
Peripheral: ++

Question 7

Action of opioids

Answer 7

Enk triggers transmembrane protein with Gi/o. This decreases Ca2+ (in) channels and increases K+ (out) channels,
Hyperpolarisation
It also decreases the conversion of AMP to cAMP and thus PKA.

Question 8

Opioids and neurotransmitters

Answer 8

Increase action of glutamate and decrease GABA in the PAG - reducing signals to raphe nucleus
Increases action of 5HT and noradrenaline which activate inhibitory interneurons

Question 9

Opioid receptor agonists

Answer 9

Agonists of all three receptors cause analgesia
µ receptor agonists are dangerous because of their euphoric effects and respiratory depression = overdose.
κ and δ may be safer, but dysphoria and proconvulsant side effects limit their use.

Question 10

Opiates and K channels

Answer 10

Opiates activate the opioid/cannabinoid receptor
Activates potassium channels
Inhibitory

Question 11

Desirable effects of µ-opioid receptor activation

Answer 11

Analgesia
Euphoria (contributes to analgesia)
Constipation (helps for diarrhoea)
Sedation (helps for insomnia)
Cough suppression

Question 12

undesirable effects of µ-opioid receptor activation

Answer 12

Respiratory depression
Euphoria (problem for addiction)
Constipation (methylnaltrexone fixes)
Sedation (bad for use long term)
Nausea and vomiting
Tolerance
Itching
Psychological dependence (addiction)
Physical dependence (withdrawal)

Question 13

Effect of increasing potency of opioids on side effects

Answer 13

All side effects are caused by the activation of the µ-opioid receptor, so increasing analgesic potency increases the side effects too.

Question 14

Morphine and heroine

Answer 14

Heroine is an adapted version of morphine that was designed to be safer.
Can pass through the blood-brain barrier more effectively and when in the brain it is metabolised to morphine.
It is essentially just a way of getting morphine into the brain faster.

Question 15

Opiates - pills

Answer 15

Morphine/codeine

Question 16

Opiates - intravenous injection

Answer 16

Patient controlled injection
Morphine / diamorphine / fentanyl

Question 17

Epidural

Answer 17

Delivered into the cerebrospinal fluid
Fentanyl / pethidine

Question 18

Transdermal patch

Answer 18

Works well with lipophilic drugs
Good for maintaining stable levels, due to slow nature of action.
Fentanyl / buprenorphine

Question 19

Lollipop

Answer 19

Fentanyl can enter the blood supply through the cheek and tongue

Question 20

Opioids in the PAG

Answer 20

Increased Glutamate
Decreased GABA
Increased signal to raphe magnus

Question 21

Opioid inhibition in the dorsal horn

Answer 21

Descending input from PAG/locus coeruleus/raphe nuclei
5HT or noradrenaline increase action of enkephalin (inhibitory) interneurons
Opioids increase 5HT and noradrenaline