Opioids

Question 1

What is the definition of opioids?

Answer 1

Naturally occurring, synthetic or semi-synthetic compounds which act at opioid receptors

Question 2

What are the effects of opioids?

Answer 2

Surge of pleasurable sensation, reduced stress and anxiety, impaired mental function, slowed cardiac and respiratory function, reduced pain

Question 3

The two acetyl compounds of diacetylmorphine (heroin) make it easier to what?

Answer 3

Cross the BBB

Question 4

What is the generic structure of metenkephalin and leuenkephalin?

Answer 4

Tyr - Gly - Gly - Phe - Met/Leu

Question 5

What are met and leu generated from?

Answer 5

Proenkephalin

Question 6

What ratio of met to leu in proenkephalin?

Answer 6

4:1

Question 7

All endogenous opioids feature…?

Answer 7

The same N terminal sequence of either metenkephalin or leuenkephalin

Question 8

Which fibres are used to signal non-noxious mechanical stimuli?

Answer 8

A beta fibres

Question 9

Which fibres are used to signal noxious mechanical stimuli?

Answer 9

A delta fibres

Question 10

C fibres are used to transmit what sort of stimuli?

Answer 10

Noxious heat and chemical stimuli

Question 11

Which types of fibres are nociceptive?

Answer 11

A delta and C fibres

Question 12

What is coding of intensity?

Answer 12

Action potentials occur more frequently when a stimulus is more painful or increased and vice versa

Question 13

what is coding of intensity recruitment?

Answer 13

More neurons are recruited in the presence of a more painful stimulus, leading to increased frequency of action potentials.

Question 14

What is the endogenous descending control of nociception?

Answer 14

5HT neurons act on 5HT1A receptors to reduce activity of spinal projection neurons at a positive 5HT receptor to stimulate GABAergic neurons to also inhibit.
5HT can also bind to positive receptors on enkephalinergic interneurons to release metenkephalin and leuenkephalin to depress glutamate release from primary afferents and postsynaptically by activating K+ channels to hyper polarise - making it less like to have an EPSP.

Question 15

What are the major sites of analgesic opioid action?

Answer 15

Periacqueductal Grey - opioid receptor activation causes activation of PAG projection neurons by inhibiting the ongoing synaptic inhibition they receive.
Presynaptic terminals of primary afferent nociceptors - depresses release of glutamate and thus synaptic excitation

Question 16

What are the side effects of opioids?

Answer 16

Addiction, tolerance, sedation, itching, dry mouth, dizziness, nausea, vomiting, respirator depression and constipation.

Question 17

Why does constipation occur during opioid use?

Answer 17

Opioid receptors are distributed throughout the GI tract. GI motility relies on fine balance between excitatory and inhibitory release of neurotransmitters by mesenteric neurons - this is redeuced by opioids leading to neuronal mediated blockade of secretomotor GI function - abnormal coordination of smooth muscle contraction and relaxation.

Question 18

What is the solution to opioid-induced constipation?

Answer 18

Peripherally restricted mu opioid antagonists e.g. Alvimopan has low lipid solubility so doesn’t cross the BBB and is poorly absorbed so concentrated in the GI tract.

Question 19

Why does overdose often happen in relapse?

Answer 19

Because opioid tolerance develops when you are taking the drugs, during withdrawal the tolerance reverses - but people may relapse and take the dose they used to, which can now kill them.

Question 20

What is the pathway that leads to tolerance?

Answer 20

Phosphorylation > beta arrestin binding > endocytosis of receptor > tolerance

Question 21

What is evidence that beta arresting is involved in the development of tolerance?

Answer 21

Beta arrestin knockout mice do not develop antinociceptive tolerance.

Question 22

Why is fentanyl more potent in vivo than in vitro?

Answer 22

because it is very lipophilic, so crosses the blood brain barrier quickly.