Core pharmacology

Class Group

Non-Opiate Analgesic

Legacy Cicm Level

Level 1

Introduction

Acetanalide derivative

Indications Uses

Analgesia
Anitpyretic

Presentation

Tablets, IV formulation with 10mg/mL containing mannitol, Combination formulations with codeine and non-steroidals

Mechanism of action

Not entirely elucidated
1. Reduced prostaglandin synthesis in areas of inflammation ? COX 3 inhibition
a) ↓ PGE2 in Hypothalamus → Anti-pyretic effect
2. Analgesic Effect
a) ↓’d central serotonergic reuptake → ↑ descending
b) 5HT agonist → enhanced descending inhibitory pain pathways.
c) Central inhibition of endocannabinoid uptake
d) Peripheral afferent nociceptive chemoreceptor impulse blockade via bradykinin inhibition
synergistic with opioid medications,
reducing the overall opioid requirement by 20-30%

Onset Peak Duration

onset / duration PO <1 hr / 4-6 hrs, IV 10-15mins / 4-6 hrs

Physiological effects

Functional class: Antipyretic, Analgesic
Indications: Mild-moderate pain, Opioid sparing, Antipyretic

Adverse Effects Toxicity

Very safe SE profile. Safe in ped,preg.
Toxicity – hepatic and renal toxicity. plasma levels should be plotted on a nomogram and consideration of NAC infusion commenced as appropriate. ALT is a marker of damage.

Absorption

PO bioavailability 60-90% (Small intest)

Distribution

Lipid solubility intermediate
pKa 9.5

Protein binding

Low protein binding (5%)

Volume of distribution

Vd = 1L/kg

Metabolism

Metabolised by the liver to glucuronide, sulphate and cysteine conjugates.

Excretion

Renal excretion of glucuronide, sulphide metabolites. Inactive, build up in renal failure.

Half-life

half life ~2 hours
- prolonged in overdosage and renal dx.

Route And Dose

Route: Tablets, IV
Dose: 15mg/kg to 1g QID