Core pharmacology

Class Group

Opiate Analgesic

Legacy Cicm Level

-

Introduction

Pure opioid
Semi-synthetic hydrogenated ketone derivative of morphine
naturally occurring phenanthrene alkaloid which is a methylated morphine derivative

Indications Uses

1. pain of mild to moderate severity
2. diarrhoea and excessive ileostomy output and
3. as an antitussive agent and
4. traditionally to provide analgesia for head-injured patients

Presentation

Codeine phosphate

Tab: 15/30/60mg
Syrup: 5mg/ml
Inj: Clear colorless solution 60mg/ml

Often in fixed dose preparations with paracetamol, ibuprofen or aspirin

Main Action

very low affinity for opioid receptors.

10% metabolized to morphine - analgesic and constipating effects.

antitussive effects of
codeine mediated by specific high-affinity codeine receptors

Mechanism of action

Binds primarily to inhibitory G-Protein Coupled μ-opioid receptors→ ↑adenylyl cyclase→ ↓cAMP→ hyperpolarization of cell→↓neurotransmitter release

Onset Peak Duration

IM absorption ~0.5hrs peak 1hr

Physiological effects

inhibitory action,
modulating the pain response to produce analgesia.

Opioid Effects from Morphine metabolite.

Antitussive effects

Adverse Effects Toxicity

Markedly inhibits GIT motility – constipation

Nausea, vomiting
Dizziness
Excitatory phenomena

Cardiovascular collapse in overdose or IV administration

Reports of Bowel perforation sec to dec GIT transit

Low propensity for dependence

Absorption

PO BA 60-70%

Little first pass metabolism

Protein binding

7%

Volume of distribution

5.4 L/kg

Metabolism

Liver – extensive.
Major Metabolites: Morphine (O-demethylation), codeine-6-glucuronide (glucuronidation),
Norcodeine (N-demethylation)

CYP2D6 genetic variability:
‘Fast’ metabolizers produce more morphine

Excretion

Urine –
17% unchanged
Rest metab

Half-life

2.8hrs

Special Points

Dose to be reduced in renal failure

Route And Dose

PO/IM: 30-60mg Q6-Q6hrly
Rectal: 1mg/kg

Not given IV due to hypotension sec histamine release

(relative potency 0.1)