Core pharmacology

Class Group

Opiate Analgesic

Legacy Cicm Level

Level 1

Introduction

naturally occuring phenanthrene derivative from papaver somniferum plant

Indications Uses

1. for premedication
2. as an analgesic in the management of moderate to severe pain
3. in the treatment of left ventricular failure
4. to provide analgesia during terminal care, and
5. in combination with kaolin in the symptomatic treatment of diarrhoea

Presentation

either as a clear liquid for injection, orally in immediate (liquid or tablet) and sustained release (MS Contin)

Main Action

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

Physiological effects

CNS:
Opioid receptors present in cerebral cortex, periaqueductal grey, nucleus accumbens, area postrema, thalamus and NTS
- Analgesia
- Sedation
- Respiratory depression
- Nausea
- Euphoria
- Psychotomimetics
Seizures (due to M6G metabolite)

PNS Excitatory action
Histamine release

Adverse Effects Toxicity

CNS: dysphoria, confusion, ↓LoC, ↓cough reflex, miosis(PNS)
CVS: hypotension (↓TPR, blunt baroreceptor reflexes)
Resp: dir ↓resp drive indir via obtundation
GI: ↓gut motility, ↓SB secretions, CTZ→N+V, constipn, CBD spasm.
GU: Urinary retention
skin flushing, pruritis(histamine)
Dependence, addiction,Tolernce. IT – resp dep (rostral migration)

Absorption

PO/IV/IM/SC/SL/IT
Poor bioavailability 30% (good abs but high 1st pass metab)
onset / duration Oral ~30 minutes; I.V.: 5-10 minutes

Distribution

relative lipid sol 1

but crosses BBB

pKa 8.0 (25% unionised)
slow redistribution

Protein binding

prot bind 20-40% (Alb)

Volume of distribution

mod Vd 3-4L/kg

Metabolism

Metabolised to morphine-3-glucuronide (70%)
and morphine-6-glucuronide (10%) by gut wall and liver.
M6G is 10-20 times potent, may accumulate in renal failure

Excretion

Excreted mainly in urine as conjugates with 10% in faeces

Half-life

Half time 2-4hrs (large interpatient Variability)

Special Points

May precipitate encephalopathy in hepatic failure
May precipitate coma in hypopituitarism

Good reversal with naloxone (does not affect epidural analgesia)

Not removed by haemo/peritoneal dialysis

Route And Dose

Dose 5-10mg titrate eff¬ect, may increase x100 with tolerance

(relative potency 1)