Opioids

Question 1

Central effects of opioids

Answer 1

Psychoactive I.e euphoria

Question 2

Peripheral effects of opioids

Answer 2

Inhibit substance P release from presynaptic nerve

Question 3

Explain gate theory of pain

Answer 3

Pain signals come from A or C fibres and goes through the substantia gelatinosa in spinal cord and can be modulated (gate opened or closed)
Thalamus processes pain signals and only strong signals will be transmitted to primary sensory cortex

Question 4

What are the endogenous opioids and what molecules are they derived from. Give an example of each

Answer 4

Enkephalins e.g metenkephalin, leukenkephalin - derived from proenkephalin)
Endorphins e.g beta endorphin - derived from POMC
Dynorphins - derived from prodynorphin

Question 5

What are the opioid receptors and where do they act

Answer 5

Mu - supraspinal
Kappa - spinal cord
Delta - widely distributed

All GPCRs

Question 6

Main consequence of Mu receptor activation

Answer 6

Increase K efflux via GIRK channels which decreases excitability

Question 7

Main consequence of kappa receptor activation

Answer 7

Decrease calcium influx

Question 8

Main consequence of delta receptor activation

Answer 8

Decrease cAMP synthesis which leads to less calcium influx

Question 9

Net effect of opioid receptor activation

Answer 9

Decreased release of neurotransmitter, especially substance P

Question 10

Which opioid receptor is most responsible for side effects

Answer 10

Mu

Question 11

Mu binding side effects of opioids

Answer 11

N&V
Constipation
Drowsiness
Meiosis 
Respiratory depression
Hypotension

Question 12

Kappa binding opioid side effects

Answer 12

Dysphoria - confusion

Question 13

What’s a partial agonist of opioid receptors

Answer 13

Buprenorphine

Question 14

What’s an antagonist of opioid receptors

Answer 14

Naloxone

Question 15

Chemical structure of morphine and what does this allow

Answer 15

2 OH groups - makes it poorly lipophilic so it goes straight into phase 2 metabolism and is broken down rapidly to an active metabolite (morphine-6-glucoronide)

Question 16

Chemical structure of diamorphine and what does this allow

Answer 16

2 acetyl groups - makes it more lipophilic than morphine so it rapidly crosses BBB
Ester bonds - rapidly hydrolysed by pseudocholinesterases to morphine
I.e diamorphine rapidly delivers large dose of morphine straight to brain

Question 17

Clinical uses of morphine

Answer 17

Palliative analgesic

Diarrhoea

Question 18

Clinical uses of methadone

Answer 18

Dependence

Question 19

Clinical uses of tramadol

Answer 19

Analgesic

Antidepressant

Question 20

Clinical uses of codeine

Answer 20

Mild analgesic

Question 21

Clinical uses of fentanyl

Answer 21

Anaesthesia

Question 22

What determines dosing of codeine

Answer 22

CYP450 polymorphism as codeine is metabolised to morphine