E. The medicinal chemistry of opioid analgesics

Question 1

What does the term opioid mean?

Answer 1

Describes ALL the synthetic, semi-synthetic and naturally occuring and endogenous compounds which interact with the opioid receptors in the body

Question 2

What does the term opium mean?

Answer 2

Describes the narcotic analgesic compounds which are structurally related to morphine .

Question 3

What are the clinical uses of opioids ?

Answer 3

Managing acute and chronic pain due to their analgesic properties.

Indications:

• Moderate to severe pain
• Cough
• Diarrhoea
• Opioid Dependance

Question 4

Name an example of an opioid that can be used for moderate to severe pain.

Answer 4

Morphine
Fentanyl
Oxymorphone
Hydromorphone

Question 5

Name and example of an opioid that can be used for cough.

Answer 5

Codeine 
Dihydrocodeine 
Ethylmorphine 
Hydromorphone 
Hydrocodone

Question 6

Name an example of an opioid that can be used for diarrhoea.

Answer 6

Loperamide
Difenoxin
Diphenoxylate

Question 7

Name an example of an opioid that can be used for opioid dependance

Answer 7

Methadone

Buprenorphine

Question 8

What are the common side effects for opioids?

Answer 8

Respiratory depression, nausea, vomiting, drowsiness, itching, dry mouth, miosis and constipation

Question 9

What are the problems associated with opioid use?

Answer 9

Tolerance
Physical dependence
Addiction

Question 10

What are the main natural analgesics that the body produces?

Answer 10

Endorphins

Enkephalins

Question 11

What are the most important enkephalins?

Answer 11

Leu-Enkephalin

Met-enkephalin

Question 12

What is an alkaloid?

Answer 12

An organic compound that contains a basic nitrogen atom

Question 13

Is morphine mostly ionised or unionised at physiological pH?

Answer 13

Ionised

Question 14

How many chiral centres does morphine have and is nitrogen one of them ?

Answer 14

5 chiral centres and nitrogen is not one of them

Question 15

Is a tertiary alaphatic amine basic or acidic ?

Answer 15

Basic

Question 16

What would happen if you modified the functional group (phenol-OH) in morphine ?

What does this conclude about the importance of phenol in morphine?

Answer 16

The analgesic activity would decrease.

The phenolic OH is important in morphine.

Question 17

Why does codeine posses 0.1% activity compared to morphine in vitro?

Answer 17

Codeine is a prodrug of morphine therefore requires enzymes within the liver to form morphine.

Question 18

What happened to the analgesic activity when the 6-OH in morphine was modified ?

Answer 18

The modification lead to a 4-5 fold increase in activity. The inversion of alcohol, removal or oxidation to ketone led to compounds with increased or similar activity

Question 19

In vivo what has the most analgesic activity.

morphine, 6-acetylmorphine, 3,6-diacetylmorphine

Answer 19

6-acetylmorphine
3,6-diacetylmorphine
Morphine

Question 20

Why is 6-acetylmorphine and heroin possess more activity than morphine?

Answer 20

Highly lipophilic molecules than the more polar morphine molecule. This means that they have a higher chance of reaching the receptor.

A greater percentage of heroin can cross the lipid BBB. Only the neutral form can cross the BBB. Once it reaches the brain cells, the esterases must metabolise the groups to make a phenolic group exposed. this is when it is able to act on the receptor to produce the analgesic effects