Core pharmacology

Class Group

Opiate Analgesic

Legacy Cicm Level

Level 2

Introduction

Pure opioid
Semi-synthetic hydrogenated ketone derivative of morphine

Indications Uses

1. as an analgesic in the management of moderate to severe pain – acute and chronic

Presentation

Inj: Clear solution with slightly different refractive index from water. May acquire amber discoloration if exposed to light (with no effect on potency)

Tablets, liquid, suppositories

Main Action

Same as morphine

primarily CNS μ receptor activity, also κ and δ.

Mechanism of action

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

Onset Peak Duration

IR: Onset 15-20min, Peak 30-60min, Dur 3-4hrs

XR: Onset 6hrs, Peak 9hrs, Dur 13hrs

Physiological effects

inhibitory action,
modulating the pain response to produce analgesia.

Adverse Effects Toxicity

Similar to morphine

reduced incidence of pruritus and nausea (which indicates a lower release of histamine)

Absorption

Significant first pass metabolism

PO BA 60%

Distribution

Parenteral: Rapid redistribution to liver, spleen, kidney, skeletal muscle

Protein binding

8-19%

Volume of distribution

4 L/kg

Metabolism

Liver
Mainly to hydromorphone-3-glucuronide

Excretion

Urine – main metabolite (7% unchanged)
Faeces

Half-life

IR: 2-3hrs
XR: 8-15hrs

Special Points

Reversed by naloxone

Route And Dose

(relative potency 5-7)