Acetylcysteine Information
Acetylcysteine ()
Acetylcysteine () Description
Acetylcysteine () is the nonproprietary name for the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. Chemically, it is N-acetyl-L-cysteine.
The compound is a white crystalline powder which melts in the range of 104° to 110°C and has a very slight odor. The structural formula of Acetylcysteine () is:
CHNOS M.W.=163.19
Acetylcysteine () Solution, USP is supplied as a sterile unpreserved solution (not for injection) in vials containing a 10% (100 mg/mL) or 20% (200 mg/mL) solution of Acetylcysteine () as the sodium salt. The inactive ingredients are edetate disodium, sodium hydroxide and Sterile Water for Injection, USP. The pH of the solution ranges from 6.0 to 7.5. It is administered by inhalation or direct instillation for mucolysis, or orally for acetaminophen overdosage.
Acetylcysteine () Acetylcysteine As A Mucolytic Agent
The viscosity of pulmonary mucous secretions depends on the concentrations of mucoprotein and, to a lesser extent, deoxyribonucleic acid (DNA). The latter increases with increasing purulence owing to the presence of cellular debris. The mucolytic action of Acetylcysteine () is related to the sulfhydryl group in the molecule. This group probably “opens” disulfide linkages in mucous thereby lowering the viscosity. The mucolytic activity of Acetylcysteine () is unaltered by the presence of DNA, and increases with increasing pH. Significant mucolysis occurs between pH 7 and 9.
Acetylcysteine () undergoes rapid deacetylation to yield cysteine or oxidation to yield diAcetylcysteine () .
Occasionally, patients exposed to the inhalation of an Acetylcysteine () aerosol respond with the development of increased airways obstruction of varying and unpredictable severity. Those patients who are reactors cannot be identified from a random patient population. Even when patients are known to have reacted previously to the inhalation of an Acetylcysteine () aerosol, they may not react during a subsequent treatment. The converse is also true; patients who have had inhalation treatments of Acetylcysteine () without incident may still react to a subsequent inhalation with increased airways obstruction. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, the medication should be discontinued immediately.
After proper administration of Acetylcysteine () , an increased volume of liquefied bronchial secretions may occur. When cough is inadequate, the airway must be maintained open by mechanical suction if necessary. When there is a mechanical block due to foreign body or local accumulation, the airway should be cleared by endotracheal aspiration, with or without bronchoscopy. Asthmatics under treatment with Acetylcysteine () should be watched carefully. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, the medication should be discontinued immediately.
Adverse effects have included stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness and bronchoconstriction. Clinically overt Acetylcysteine () induced bronchospasm occurs infrequently and unpredictably even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma.
Acquired sensitization to Acetylcysteine () has been reported rarely. Reports of sensitization in patients have not been confirmed by patch testing. Sensitization has been confirmed in several inhalation therapists who reported a history of dermal eruptions after frequent and extended exposure to Acetylcysteine () .
Reports of irritation to the tracheal and bronchial tracts have been received and although hemoptysis has occurred in patients receiving Acetylcysteine () such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship has not been established.
Acetylcysteine () Acetylcysteine As An Antidote For Acetaminophen Overdosage
(Antidotal) Acetaminophen is rapidly absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. The parent compound, which is nontoxic, is extensively metabolized in the liver to form principally the sulfate and glucuronide conjugates which are also nontoxic and are rapidly excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by the cytochrome P-450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite which preferentially conjugates with hepatic glutathione to form the nontoxic cysteine and mercapturic acid derivatives which are then excreted by the kidney. Therapeutic doses of acetaminophen do not saturate the glucuronide and sulfate conjugation pathways and do not result in the formation of sufficient reactive metabolite to deplete glutathione stores. However, following ingestion of a large overdose (150 mg/kg or greater) the glucuronide and sulfate conjugation pathways are saturated resulting in a larger fraction of the drug being metabolized via the P-450 pathway. The increased formation of reactive metabolite may deplete the hepatic stores of glutathione with subsequent binding of the metabolite to protein molecules within the hepatocyte resulting in cellular necrosis.
Acetylcysteine () has been shown to reduce the extent of liver injury following acetaminophen overdose. Its effectiveness depends on early oral administration, with benefit seen principally in patients treated within 16 hours of the overdose. Acetylcysteine () probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.
Generalized urticaria has been observed rarely in patients receiving oral Acetylcysteine () for acetaminophen overdose. If this occurs or other allergic symptoms appear, treatment with Acetylcysteine () should be discontinued unless it is deemed essential and the allergic symptoms can be otherwise controlled.
If encephalopathy due to hepatic failure becomes evident, Acetylcysteine () treatment should be discontinued to avoid further administration of nitrogenous substances. There are no data indicating that Acetylcysteine () influences hepatic failure, but this remains a theoretical possibility.
Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment with oral Acetylcysteine () may aggravate the vomiting. Patients at risk of gastric hemorrhage (e.g., esophageal varices, peptic ulcers, etc.) should be evaluated concerning the risk of upper gastrointestinal hemorrhage versus the risk of developing hepatic toxicity, and treatment with Acetylcysteine () given accordingly.
Dilution of the Acetylcysteine () (See ) minimizes the propensity of oral Acetylcysteine () to aggravate vomiting.
Acetylcysteine () Dosage Guide And Preparation
Doses in relation to body weight are:
Acetylcysteine () How Supplied
Acetylcysteine () Solution, USP, is available in rubber stopped glass vials containing 10 or 30 mL. The 20% solution may be diluted to a lesser concentration with either Sodium Chloride for Injection, Sodium Chloride for Inhalation, Sterile Water for Injection, or Sterile Water for Inhalation. The 10% solution may be used undiluted.
Acetycysteine is sterile, and can be used for inhalation (mucolytic agent) or oral administration (acetaminophen antidote). It is available as follows:
10% Acetylcysteine () Solution, USP (100 mg Acetylcysteine () per mL). 10 mL vials; carton of 3 30 mL vials; carton of 3
20% Acetylcysteine () Solution, USP (200 mg Acetylcysteine () per mL). 10 mL vials; carton of 3 30 mL vials; carton of 3
Acetylcysteine ()
Acetylcysteine () Vial Label %, Ml
Acetylcysteine () Vial Label %, Ml
Acetylcysteine () Vial Label %, Ml
Acetylcysteine () Vial Label %, Ml
