ACETYLCYSTEINE

Acetylcysteine is used dog and cats as an antidote (acetaminophen/paracetamol toxicosis in cats), antioxidant, mucolytic agent, to prevent contrast medium nephropathy, etc.

Acetylcysteine also known as N-acetylcysteine and NAC. It is a sulfahydryl compound.

MECHANISM OF ACTION

Acetylcysteine decreases the viscosity of secretions and is used as a mucolytic agent (Acetylcysteine splits disulphide bonds in mucoproteins and thus lowers mucus viscosity, resulting in a larger volume of sputum.) in the eyes and in bronchial nebulising solutions. Acetylcysteine is a sulfahydryl compound and acts to increase the synthesis of glutathione in the liver. Glutathione subsequently acts as an antioxidant and facilitates conjugation to toxic metabolites, particularly the toxic metabolites of acetaminophen/paracetamol. The antioxidant effects also have been used to treat conditions associated with oxidative stress. The pharmacokinetics have been studied in cats. It has a half-life of approximately 1.5 hours and oral absorption of 33%. The clearance is faster than in humans.

CLINICAL USES

As a donor of the sulfhydryl group, it is used as an antidote for intoxications (e.g., acetaminophen/paracetamol toxicosis in cats). It acts to replenish glutathione in animals that have been intoxicated with drugs that have reactive metabolites. When treating poisoning, it is important that acetylcysteine be administered as soon as possible for optimum effectiveness. Acetylcysteine has also been used to prevent contrast medium induced nephropathy. Acetylcysteine has been used as a treatment of oxidative stress because it is a scavenger of hydroxyl radicals and hypochlorous acid. It has also been used to treat heavy metal toxicosis when administered with chelating agents. Acetylcysteine can reduce cerebral edema, but this has not produced any established clinical uses.

SIDE EFFECTS

Allergic reactions have been reported in people, which resemble anaphylactic reactions when it is given IV. These reactions manifest as skin reactions, bronchospasm, tachycardia, and hypotension. Vomiting has been observed in cats, but this also may be caused by the toxicant (acetaminophen/paracetamol). When delivered via aerosol to the airways of cats, it increases airway resistance and could worsen airway disease in cats.

CONTRAINDICATIONS

Acetylcysteine may cause sensitization with prolonged topical administration. It may react with certain materials in nebulizing equipment. Avoid delivering via aerosol to the airways of cats because it might worsen clinical airway disease. Because acetylcysteine is hyperosmolar (2600 mOsmol/L), it must be diluted in sterile water prior to injection. Visually inspect for particulate matter and discolouration prior to injection.

DRUG INTERACTIONS

Acetylcysteine acts to donate sulfhydryl groups and may facilitate drug conjugation.

PRECAUTIONS

Available as an agent for decreasing viscosity of respiratory secretions, but most common use is as a treatment for intoxications, primarily for cats to treat acetaminophen/paracetamol toxicosis. When treating an intoxication, doses are listed here, but also consult a poison control center for specific guidelines. The doses used in cats (and listed in the dosing section) are extrapolated from dosages used in humans for treatment of intoxication. However, pharmacokinetics are different in cats (shorter half-life and faster clearance), and higher doses may be needed in severe cases. For treatment of oxidative stress, constant rate infusions (CRIs) have been used in which 50 mg/kg is diluted 1:4 in saline solutions and administered IV over the course of 1 hour. Alternatively, the injection can be administered IV as a loading dose (150 mg/kg) over 60 minutes, followed by 50 mg/kg over the next 4 hours, and 100 mg/kg over the next 16 hours (21-hour total treatment time).

When administered by injection, the solution is hyperosmolar and must be diluted first. Diluent for dilution can include 0.45% NaCl, 5% dextrose, or sterile water.

MONITORING

When used to treat acetaminophen/paracetamol toxicity, monitor complete blood count (CBC) and liver enzyme concentrations.

FORMULATIONS

Injectables:

6 g of acetylcysteine in 30 mL vials for IV use (200 mg/mL). 200 mg/mL ampoules (Mucomix) also available.

Tablets:

500mg and 2.5g acetylcysteine tablets available.

An effervescent tablet of acetylcysteine (Cetylev) also is available and used in people to decrease hepatic injury caused by high doses of acetaminophen/paracetamol.

Syrup/Suspensions:

Acetylcysteine is available in a 20% oral solution (200 mg/mL).

Other formulations:

Nasal (nebulisation; Mucyst), and topical (eye) also available.

STORAGE

Acetylcysteine is unstable in air and easily oxidizes. It should be protected from light. Discard open vials after 96 hours. The normal color of the solution ranges from colorless to a slight pink or purple after the stopper is punctured. This color change does not affect the quality of the product. After dilution, the solution can be stored for 24 hours at room temperature. Discard unused portion if stored for longer.

DOSE RATE

Dose rates for various animals are listed below. Adjust the dose rates according to the pathophysiology and condition of each case.

DOGS & CATS

Antidote: 140 mg/kg (loading dose); then 70 mg/kg q4h IV or PO for five doses.
Eye solution: 2% solution topically q2h.
To prevent contrast-medium nephropathy: 17 mg/kg IV bolus followed by 17 mg/kg q12h for 48 hours.
CRIs have been used to treat oxidative stress (50 mg/kg diluted in saline infused over 1 hour).

ADMINISTRATION

Acetylcysteine typically administered via intravenous (IV), intramuscular (IM), subcutaneous (SC), per oral (PO), nasal (nebulisation), and topical (eye) routes. It is essential to check the label for specific preparation instructions since certain formulations may be designated for specific routes of administration.

ORAL BIOAVAILABILITY

A bioavailability of 33% can be expected for Acetylcysteine when administered orally.

PROTEIN BINDING

Protein binding for acetylcysteine ranges from 66% to 87%.

ELIMINATION HALF LIFE

The elimination half-life of acetylcysteine is approximately 1.5 hours.

METABOLISM

Metabolism of Acetylcysteine takes place in the Liver.

EXCRETION

Excretion of Acetylcysteine takes place in the Kidneys.

ANTIDOTE

No specific antidote.

NOTES

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