Codeine

Question 1

What class of opioid is codeine

Answer 1

Phenanthrene - naturally occuring alkaloid

3-methyl-morphine

Question 2

Describe the presentation

Answer 2

Tablets or suspension (30mg)

Often in combination with paracetamol

Question 3

What is the mechanism of action of codeine

Answer 3

Codeine has a low affinity for opioid receptors (x10 less potent than morphine)
Metabolised to various metabolites with one being morphine which then acts at mu receptor
Other metabolites have no opioid agonist activity

Question 4

Describe the main effects of codeine

Answer 4

Analgesia as per morphine with less nausea/vomiting, less sedation, less abuse potential
Constipation
Antitussive

Question 5

What is the oral bioavailability

Answer 5

60-70% as the methyl group protects it from conjugation

Question 6

How much is protein bound

Answer 6

7%

Question 7

How is codeine metabolised

Answer 7

3 metabolic pathways
6-hydroxy glucuronidation (60-70%) -> inactive
O-demethylation (5-15%) -> morphine
N-demethylation (10-20%) -> norcodeine (inactive)

Question 8

Why is genetic polymorphism important for codeine metabolism

Answer 8

O-demethylation uses CYP2D6 which exhibits genetic polymorphism
Some ethnic groups are poor metabolisers of codeine and will experience very little pain relief as codeine is only metabolised to inactive metabolites
~30% of Hong Kong Chinese, ~10% of the UK
Other groups are ultra-fast metabolisers and may be at risk of opioid toxicity, including life-threatening resp depression because of the augmented metabolism

Question 9

How is codeine excreted and what is the elimination half life

Answer 9

Metabolites excreted in the urine
5-15% excreted unchanged
T1/2 = 3.5hrs