Core pharmacology

Class Group

Opiate Analgesic

Legacy Cicm Level

Level 3

Introduction

synthetic phenylpiperidine.
μ receptor agonist

Indications Uses

1. to provide the analgesic component in general anaesthesia
2. in sedation regimens for intensive care, and
3. to obtund the cardiovascular responses to laryngoscopy.

Presentation

colourless solution containing 500mcg/ml in 2 of 5ml vials

Main Action

Same as Morphine
PK features, esp pKa ensure however significant differences to the related opioids such as fentanyl.

Mechanism of action

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

Physiological effects

inhibitory action,
modulating the pain response to produce analgesia.

Adverse Effects Toxicity

Same as other opioids

10x variability in clearance due to interpersonal variability of CYP3A4

Absorption

IV

onset / duration rapid / 30-60 minutes

Distribution

relative lipid sol 90

rapid redistribution
pKa 6.5 (95% union) BBB more rapidly

Protein binding

prot bind 85-90%

Volume of distribution

Vd 0.5L/kg

Metabolism

Liver by N – demethylation.
Compared to Fent:
only 10% pulm uptake , lower clearance rate but shorter t1/2.

Excretion

excretion urine

Half-life

half life 1.5 hours (shorter context sensitive compared to fentanyl)

Special Points

Half life prolonged in elderly, debilitated, hepatic and renal impairment

Dialysis - Unknown

Route And Dose

7mcg/kg-50 mcg/kg ventilatd

(relative potency 10-20)