Acetylcysteine (Parvolex)

Acetylcysteine - is an effective antidote to paracetamol if administered within 8 hours after an overdose.Although the protective effect diminishes progressively as the overdose–treatment interval increases, acetylcysteine can still be of benefit up to 24 hours after the overdose. In paracetamol overdose the hepatotoxicity is due to formation of a toxic metabolite. Hepatic reduced glutathione inactivates the toxic metabolite by conjugation, but glutathione stores are depleted with hepatotoxic doses of paracetamol. Acetylcysteine, being a sulphydryl (SH) group donor, protects the liver probably by restoring depleted hepatic reduced glutathione or by acting as an alternative substrate for the toxic metabolite.

Acetylcysteine may have significant cytoprotective effects.The cellular damage associated with sepsis, trauma, burns, pancreatitis, hepatic failure and tissue reperfusion following acute MI may be mediated by the formation and release of large quantities of free radicals that overwhelm and deplete endogenous antioxidants (e.g. glutathione). Acetylcysteine is a scavenger of oxygen free radicals. In addition, acetylcysteine is a glutathione precursor capable of replenishing depleted
intracellular glutathione and, in theory, augmenting antioxidant defences.

Acetylcysteine can be used to reduce the nephrotoxic effects of intravenous contrast media.Possible mechanisms include scavenging a variety of oxygen-derived free radicals and the improvement of endotheliumdependent vasodilation.

Nebulised acetylcysteine can be used as a mucolytic agent. It reduces sputum viscosity by disrupting the disulphide bonds in the mucus glycoproteins and enhances mucociliary clearance, thus facilitating easier expectoration.

Uses:
Paracetamol overdose
Antioxidant (unlicensed)
Prevent contrast-induced nephropathy (unlicensed)
Reduce sputum viscosity and facilitate easier expectoration (unlicensed)
As a sulphydryl group donor to prevent the development of nitrate tolerance (unlicensed)

Administration:
Paracetamol overdose
• IV infusion: 150 mg/kg in 200 ml glucose 5% over 15 min, followed by 50 mg/kg in 500 ml glucose 5% over 4 h, then 100 mg/kg in 1 litre glucose 5% over the next 16 h

Weight (kg)	Initial	Second	Third
	150mg/kg in 200 ml glucose 5% over 15 min	50mg/kg in 500 ml glucose 5% over 4 h	100mg/kg in 1 litre glucose 5% over 16 h
	Parvolex (ml)	Parvolex (ml)	Parvolex (ml)
50	37.5	12.5	25
60	45.0	15.0	30
70	52.5	17.5	35
80	60.0	20.0	40
90	67.5	22.5	45
x	0.75x	0.25x	0.5x

For children > 20 kg: same doses and regimen but in half the quantity of IV fluid

Hours after ingestion

Patients whose plasma concentrations fall on or above treatment line A should receive acetylcysteine. Patients with induced hepatic microsomal oxidase enzymes (for chronic alcoholics and patients taking enzymeinducing drugs are susceptible to paracetamol-induced hepatotoxicity at lower paracetamol concentrations and should be assessed against treatment line B.

Antioxidant
• IV infusion: 75–100 mg/kg in 1 litre glucose 5%, give over 24 h (rate 40 ml/h)

Prevent contrast-induced nephropathy
• IV bolus 1200 mg pre-contrast, then after 12 hours 1200mg PO/NG (or IV if nil-by-mouth) 12 hourly for 48 hours

Reduce sputum viscosity
• Nebulised: 4 ml (800 mg) undiluted Parvolex (20%) driven by air, 8 hourly Administer before chest physiotherapy

How not to use acetylcysteine
Do not drive nebuliser with oxygen (oxygen inactivates acetylcysteine)

Adverse effects
Anaphylactoid reactions (nausea, vomiting, flushing, itching, rashes,
bronchospasm, hypotension)
Fluid overload

Cautions
Asthmatics (risk of bronchospasm)
Pulmonary oedema (worsens)
Each 10ml ampoule contains Na+ 12.78mmol (up total body sodium)