Reversibly inhibits COX 1 and 2 enzymes
causing decreased production of prostaglandin precursors

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%

As an anti-inflammatory, anti-pyretic and mild analgesic

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

Rapidly absorbed
85% bioavailability

PO bioavailability 60-90% (Small intest)

pKa 4.5, weak acid therefore mostly unionised, abs via gut and SB

Lipid solubility intermediate
pKa 9.5

99% protein bound (may displace highly protein bound drugs such as warfarin altering PD properties)

Low protein binding (5%)

Very small Vd 0.1L/kg

Vd = 1L/kg

hepatic via oxidation

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

excreted as metabolites in urine 1% unchanged

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

half life 2-3 hours

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

Worsen renal function by inhibiting PGE2 and causing vasoconstriction.
 risk of thromboembolic events.
Increased risk of GI bleeding and ulceration, GORD.
Impair platelet function
May reduce the beneficial eff¬ects of aspirin

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.

Non-Opiate Analgesic

Non-Opiate Analgesic

Analgesia
Antipyretic
Antiinflammatory

Analgesia
Anitpyretic

non selective cycloxygenase inhibitor

Acetanalide derivative

Level 3

Level 1

onset 30 mins, duration 6 hours

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

200mg tablets, some formulations in combination with codiene

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

Tablets for PO/PR

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