Paracetamol

Paracetamol - the efficacy of single-dose IV paracetamol as a post-operative analgesic has been confirmed by many studies. The IV formulation provides a more predictable plasma concentration and has potency slightly less than that of a standard dose of morphine or the NSAIDs.The mechanism of action remains unclear as, unlike opioids and NSAIDs respectively, paracetamol has no known endogenous binding sites and does not inhibit peripheral cyclooxygenase activity significantly.There is increasing evidence of a central antinociceptive effect, and potential mechanisms for this include inhibition of a central nervous system COX-2, inhibition of a putative central cyclooxygenase ‘COX-3’ that is selectively susceptible to paracetamol, and modulation of inhibitory descending serotinergic pathways. Paracetamol has also been shown to prevent prostaglandin production at the cellular transcriptional level, independent of cyclooxygenase activity.

The availability of intravenous paracetamol (Perfalgan) will enhance and extend the use of this drug as a fundamental component of multimodal analgesia after surgery and in critically ill patients who are not able to absorb enterally.

Uses
Mild to moderate pain
Fever

Administration
Oral or PR: 0.5–1 g every 4–6 hours; maximum of 4 g daily
IV infusion: 1 g (100 ml) given over 15 min, every 4–6 hours;maximum
of 4 g daily

How not to use paracetamol
Do not exceed 4 g/day

Adverse effects
Hypotension with IV infusion
Liver damage with overdose

Cautions
Hepatic impairment
Renal impairment
Alcohol dependence

Organ failure
Hepatic: avoid large doses (dose-related toxicity)
Renal: increase IV infusion dose interval to every 8 hours if creatinine clearance <10 ml/min