Core pharmacology

Class Group

Opiate Analgesic

Legacy Cicm Level

Level 2

Introduction

synthetic derivative of the opioid alkaloid thebaine

Indications Uses

1. in the treatment of moderate to severe pain and has been used
2. in sequential analgesia.

Presentation

Inj:
300mcg/ml clear, colourless solution
PO: 200/400mcg tablets
TD patches

Main Action

partial agonist at MoP receptors
but dissociates slowly from the latter, leading to prolonged analgesia and low dependence

Κ: high affinity, low activity

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. (25x potent)

Adverse Effects Toxicity

Similar to morphine

CVS
Minimal (dec HR and SBP)
RS resp depression, antitussive. Histamine and tryptase release – inc PVR

Other:
Dec LH inc prolactin

Drowsiness, dizziness, headache, confusion, dysphoria, nausea vomiding

Less liable to produce dependence

Absorption

Significant firstpass orally

SL 44-94%
IM 40-90%

Distribution

Only unchanged buprenorphine reaches CNS

Protein binding

96%

Volume of distribution

3.2L/kg

Metabolism

Liver
Dralkylation and conjugation to glucuronide - Polar conjugates excreted in bile and hydrolysed by bacteria in GIT

Excretion

Faeces – unchanged
Urine – conjugated and deaklylated derivates

Half-life

5 hrs

Special Points

Partial agonists – antagonizes opioid agents and may precipitate abstinence syndromes in dependent subjects

Resp depression not completely reversed by naloxone

Not removed by haemodialysis

Route And Dose

IM/IV: 0.3-0.6mg Q6hrly
SL: 0.2-0.4mg Q6 to Q8hrly
Epidural: 0.3mg

(relative potency 25)