Acetylcysteine

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[edit] BRAND NAMES

[edit] STRUCTURE

Acetylcysteine.jpg

[edit] MECHANISM OF ACTION

N-acetylcysteine ​​(NAC) is an acetylated form of the amino acid cysteine​​. it exerts its mucolytic action through its free sulfhydryl group, which opens the disulfide bonds and lowers mucus viscosity. NAC has been demonstrated to cause a decrease in sputum consistency, to facilitate easier expectoration, and to increase sputum volume, making it a drug of choice in many respiratory diseases characterized by thick secretions.

N-acetylcysteine ​​also exerts a direct and indirect antioxidant properties. Its free thiol group (-SH) interacts and detoxifies reactive electrophiles and free radicals.

N-acetylcysteine is a precursor of glutathione as well. Glutathione is a potent antioxidant that cannot cross the cell membranes, but N-acetylcysteine easily crosses it and is converted to cysteine, an amino acid essential for the synthesis of glutathione.

At therapeutic doses, 90% of acetaminophen (Paracetamol) is metabolized in the liver to sulfate and glucuronide conjugates that are then excreted in the urine. A small portion of acetaminophen is oxidized by CYP2E1 to form N-acetyl-p-benzo-quinone imine (NAPQI). NAPQI binds covalently with hepatocyte macromolecules, producing hepatic cell lysis. With normal doses, NAPQI is rapidly conjugated with hepatic glutathione, forming a nontoxic compound which is excreted in the urine.

Liver damage due to excess NAPQI can occur in many circumstances (e.g. excessive intake of acetaminophen, excessive CYP2E1 activity due to induction by other drugs or chronic alcohol use, Competition for conjugation enzymes, depletion of glutathione stores due to malnutrition or chronic alcohol ingestion), in these circumstances, N-acetylcysteine can be administered orally or IV as an antidote to prevent or lessen hepatic injury.

[edit] INDICATIONS

  • Eye drops: To help lubricate the eye and to provide relief for dry eyes conditions which are associated with a lack of tears or abnormal tear production.
  • Oral/Nebulization: Adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions (Acute and chronic bronchopulmonary diseases and pulmonary complications of cystic fibrosis)
  • Oral/Intravenous: Antidote to prevent or lessen hepatic injury, following ingestion of toxic levels of acetaminophen.

[edit] DOSAGE

  • As a mucolytic agent (Oral route):
    • Adults: 200 mg three times daily or 600 mg once daily
    • Children 8 years and over: Adult dose
    • Children 2 to 7 years: 200 mg twice daily.
  • As a mucolytic agent (Inhalation route):
    • The recommended dose for most patients is 3-5 mL of a 20% solution three to four times a day, nebulized via aerosol
  • As an antidote for Acetaminophen Overdose (Oral route):
    • The initial dose is 140 mg / kg of body weight administered as soon as possible, within 10 hours from intoxication, followed by single doses of 70 mg/kg every 4 hours for 1-3 days.
  • Antidote for Acetaminophen Overdose (I.V. administration): The total dose is 300 mg/kg administered over 21 hours, within 24 hours of paracetamol ingestion
    • Patients who weigh 41 kg to 100 kg:
      • Loading Dose: Dilute 150 mg/kg in 200 mL of 5% dextrose and administer over 60 minutes.
      • Second Dose: Dilute 50 mg/kg in 500 mL of 5% dextrose and administer over 4 hours.
      • Third Dose: Dilute 100 mg/kg in 1000 mL of 5% dextrose and administer over 16 hours.
    • Patients who weigh 21 kg to 40 kg
      • Loading Dose: 150 mg/kg in 100 mL of diluent administered over 60 min
      • Dose 2: 50 mg/kg in 250 mL of diluent administered over 4 hr
      • Dose 3: 100 mg/kg in 500 mL of diluent administered over 16 hr
    • Patients who weigh 5 kg to 20 kg:
      • Loading Dose: 150 mg/kg in 3 mL/kg of body weight of diluent administered over 60 min
      • Dose 2: 50 mg/kg in 7 mL/kg of body weight of diluent administered over 4 hr
      • Dose 3: 100 mg/kg in 14 mL/kg of body weight of diluent administered over 16 hr

[edit] CONTRAINDICATIONS

  • Patients with previous anaphylactoid reactions to acetylcysteine.
  • Children under 2 years of age (as a mucolytic)

[edit] WARNINGS AND PRECAUTIONS

  • Serious anaphylactoid reactions, including death in a patient with asthma, have been reported in patients administered acetylcysteine intravenously. Acute flushing and erythema of the skin may occur in patients receiving acetylcysteine intravenously. These reactions usually occur 30 to 60 minutes after initiating the infusion and often resolve spontaneously despite continued infusion of acetylcysteine. Anaphylactoid reactions (defined as the occurrence of an acute hypersensitivity reaction during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath) have been observed in patients receiving I.V. acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion. If a reaction to acetylcysteine involves more than simply flushing and erythema of the skin, it should be treated as an anaphylactoid reaction. This usually entails administering antihistaminic drugs (chlorphenamine 10-20 mg IV over 1 min) and in severe cases may require administration of epinephrine and salbutamol nebs (if significant broncospasm). In addition, the acetylcysteine infusion may be interrupted until treatment of the anaphylactoid symptoms has been initiated and then carefully restarted. If the anaphylactoid reaction returns upon reinitiation of treatment or increases in severity, intravenous acetylcysteine should be discontinued and alternative patient management should be considered.
  • Use with caution in patients with asthma, or where there is a history of bronchospasm.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B (US): acetylcysteine should be used during pregnancy only when clearly needed.
  • Lactation: It is not known whether or not acetylcysteine passes into breast milk. Use caution when considering the use of acetylcysteine in lactating women.

[edit] SIDE EFFECTS

Possible side effects include: heartburn, nausea, vomiting, diarrhea, mild skin rashes, headaches and fever. Anaphylactoid reactions are rare and occur more frequently in patients treated with the i.v. preparation.

I.V Administration: Most common adverse reactions (incidence greater than 2%) are rash, urticaria/facial flushing and pruritus

See also WARNINGS AND PRECAUTIONS section

[edit] RELATED LINKS

The Health Benefits of N-Acetyl Cysteine

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Antitussives / Cough
Cough suppressants Benzonatate   Butamirate   Codeine   Dextromethorphan   Dihydrocodeine   Dropropizine   Levocloperastine   Levodropropizine   Nepinalone   Oxolamine
Mucolytics Acetylcysteine   Ambroxol (Oral)   Bromhexine   Carbocisteine   Erdosteine   Guaifenesin   Neltenexine