Opioids & Pain 💣

Question 1

What are opioid receptors

Answer 1

G-coupled protein receptors that qffext second messenger systems and K and Ca channels.

Question 2

3 types of opioid Receptors?

Answer 2

m, k, and d

Question 3

Selectivity of =
B-endorphins
Dynorphins
Encephalins

Answer 3

B-endorphins = non selective

Dynorphins = affect only k receptors

Encephalins = affect only m and d receptors

Question 4

Pharmacological effects of different opiod receptors

Table

Answer 4

M RECEPTOR =
Analgesia ✔
Resp depression ✔✔
Smooth muscle spasm ✔✔
Euphoria/sedation ✔✔

K RECEPTOR =
Analgesia ✔
DYSPHORIA+ sedation ✔

D Receptor =
Dilation of Pupil
Dysphora ✔✔
Psychotimimetic ✔

Question 5

Structure of MORPHINE

Answer 5

1. A, B, C rings = not Coplanar (looks like a T)
2. 5 rings have rigid structure
3. C, D rings hold the basic N in fixed position

Question 6

Metabolism of Codein and Morphine

Diagram

Answer 6

Question 7

Major structural features affecting activity of MORPHINE

Answer 7

1. Aromatic ring A (with 3-OH group)
2. Basic amino group in correct position:
   - NCH3 = agonist
   - N-allyl = mixed agonist/Antagonist (Nalorphine)

Question 8

HEROIN

is it a prodrug?
Is heroin or morphine better at penetrating membranes?

Answer 8

Heroin is better at penetrating membranes.

Heroin is hydrolysed to Morphine
(Heroin is a prodrug)

Question 9

CODEINE

Answer 9

1. Prodrug of morphine
2. Importance or OH group at 3 position

Question 10

Shape of C ring

Answer 10

Boat and T shape molecules

Chair and T shape molecule

Question 11

Shape of Antagnoists

Important structures

Answer 11

1. All are T-shaped
2. OH group- axial to rings C and D
3. OH group PREVENTS larger substituents on the N side to flip up because of steric effects

Question 12

What drug developments were made from Pethidine?

Answer 12

Antidiarrhoeals.
= loperamide (imodium) and
Diphenoxylate (lefenoxal)
= drugs are active in GIT, do not cross BBB.

Question 13

Pharmacology of Tramadol

Answer 13

• 1/10 the potency of morphine
• contains A and C rings
• m opioid Receptor agonist
• • serotonin reuptake inhibitor

Question 14

Pharmacology of Tapentadol

Answer 14

• benzenoid class
• only A ring
  Phenol moiety (A ring) plus tertiary amine gives rise to M-opiod Receptor effect
• m opioid Receptor agonist and
• noradrenaline reuptake inhibitor

Question 15

Metabolism of Tramadol

Answer 15

1. Metabolised by CYP2D6 =
   get O- desmethyltramadol
   x200 more affinity to m-opiods than tramadol.