Lecture 9 & 10 - Opioids Flashcards Preview

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Flashcards in Lecture 9 & 10 - Opioids Deck (48):
1

What are the CNS effects of morphine (2)

Elevates pain threshold, decreases brain awareness of pain

2

What are some of the side effects or morphine? (6)

Depression of the respiratory centre, constipation, nausea, pupil constriction, euphoria, tolerance, dependence

3

How many rings does morphine have and what shape are they in?

5 rings and T-shaped structure

4

Is morphine acidic or basic?

A functionally weak base

5

What does morphine exist as at physiological pH

Cation

6

What are the four types of opioid receptors?

MOR, KOR, DOR and ORL1 (opioid-like receptors)

7

Which receptor does morphine bind most strongly to?

MOR instead of DOR and KOR

8

What type of receptor is the opioid receptor

GPCR

9

Where does morphine bind to in the MOR?

A cavity at the extracellular edge of the receptor

10

What is the difference between opium and morphine?

Opium is an extract obtained form the opium poppy and contained more than 20 alkaloids, morphine is the main active alkaloid in opium.

11

Why can't morphine poorly absorbed in the gut?

It is polar

12

Why is octanol used to calculate the partition coefficient?

It has a long hydrocarbon tail so it mimics
the amphiphilic nature of lipid membranes

13

What logP guarantees oral absorption?

2-5

14

What percentage of morphine is unionised at pH 7.4

14%

15

What is morphine's pKA

8.2

16

What is the difference between morphine and normorphine

Normorphine has a amine group added instead of the methyl so it has increase ionisation

17

Which molecule has the highest lipophilicity?

Heroin

18

Which molecule has the highest relative analgesic activity?

6-acetylmorphine (an active metabolite of heroin)

19

Heroin is a prodrug true or false

True

20

What groups have been replaced in morphine to make heroin?

The 3-6 hydroxyl groups have been replaced with acetyl groups

21

What is codeine?

A 3-methylether of morphine

22

Is codeine a prodrug

Yes

23

Is codeine found in opium

Yes

24

How is codeine metabolised in the liver?

O-demethylation

25

What re the 3 conjugations of morphine in the liver?

Morphine 3-glucuronide
Morphine 6-glucuronide
Morphine 3,6-glucuronide

26

Which of the glucuronide conjugations of morphine is active?

Morphine 6-glucuronide

27

Which OH group is important for morphine activity

The 3 hydroxyl

28

Which confirmation of the target does an agonist stabilise?

The active conformation

29

What are the three key groups for morphine activity?

1. 3-hydroxyl forms hydrogen bonds
2. Benzene rings have Van der waals interactions
3. The N-methyl group can become charged and form ionic bonds

30

What is the 'message' responsible for?

Pharmacological activity

31

Which parts are responsible for the message in morphine?

The charged amine and phenolic group

32

What is the 'address' responsible for?

Target selectivity (MOR vs KOR)

33

What is responsible for the address portion of morphine?

The variable hydrophobic portion

34

How is oxycodone generated?

An an extra OH group at position 14

35

At which alkyl group does agonistic activity of morphine return?

Pentyl and hexyl

36

What is one of the most potent N-alkylation substitutions?

Phenethylmorphine

37

Why is naltrexone such an effective antagonist?

It has a cycylpropane group at the N-alkylation

38

Which is more rapid, naloxone or naltrexone?

Naloxone

39

Why are fentanyl and sufentanil more potent than morphine?

1. Both are highly lipophilic due to a phenylethyl on N
2. Fentanyl has a phenetyl group attached to the nitrogen ring, sufentanil has a bioisosteric replacement with thiophene

40

How is etorphine different from morphine and how does this influence potency?

Etorphine is synthesised from thebaine and is conformationall restricted

41

Which rings have been removed in pethidine and norpethidine?

B, C and D

42

What is the consequence of removing B, C and D

No 'address' concept, they bind in different manners

43

What are met and leu enkphalins

Pentapeptides with a preference for MOR and DOR

44

Dynorphin vs endorphine selectivity for receptors

KOR vs MOR and DOR

45

Which groups are essential for the activity of met-enkephalin

Tyrosine phenol and amino groups

46

How do you remove the activity of met-enkephalin (2)

Replace the tyrosine
Inactivate it using peptidase

47

What provides the message in met-enkephalin?

The tyrosine

48

Morphine vs enkephalin selectivity for for MOR, KOR and DOR

+++, ++, + vs +++, ___, +++