Rt O

Uses

Acetylcysteine is used for an adjunctive treatment for patients with abnormal, viscid or inspissated mucus secretions associated with conditions such as-

Acute and chronic bronchopulmonary disorders (e.g. pneumonia, bronchitis, emphysema, tracheobronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis, primary amyloidosis of the lung) Atelectasis caused by mucus obstruction Pulmonary complications of cystic fibrosis Pulmonary complications of thoracic and cardiovascular surgery Post-traumatic chest conditions.

It is effective in all respiratory airways disease causing formation of a dense secretion that cannot be or can only partially be expectorated such as acute and chronic bronchitis, laryngitis, sinusitis, tracheitis, infuenza & bronchial asthma. Acetylcysteine is also used for the treatment of Paracetamol overdose. Treatment option is optimal if given within 8 hours of Paracetamol ingestion.

• • Acute and chronic diseases of respiratory tracts associated with viscid mucus including acute and chronic bronchitis
• • Productive cough
• • Inflammatory diseases of Rhinopharyngeal tract (e.g. Laryngitis, Pharyngitis, Sinusitis and Rhinitis) associated with viscid mucus
• • Asthmatic bronchitis, Bronchial asthma with difficult departure of mucus
• • Bronchiectasis
• • Chronic pneumonia.

Rt O is also used to associated treatment for these conditions: Acetaminophen Overdose, Chronic Rhinitis, Corneal Diseases, Corneal ulceration, Crusting Rhinitis, Keratopathy, Rhinitis, Sinusitis, Vasomotor Rhinitis, Acute Rhinitis, Subacute Rhinitis, Airway secretion clearance therapyAirway secretion clearance therapy

How Rt O works

A number of possible mechanisms for the mucolytic activity of acetylcysteine have been proposed. Acetylcysteine's sulfhydryl groups may hydrolize disulfide bonds within mucin, breaking down the oligomers, and making the mucin less viscous. Acetylcysteine has also been shown to reduce mucin secretion in rat models. It is an antioxidant in its own right but is also deacetylated to cysteine, which participates in the synthesis of the antioxidant glutathione. The antioxidant activity may also alter intracellular redox reactions, decreasing phosphorylation of EGFR and MAPK, which decrease transcription of the gene MUC5AC which produces mucin.

In the case of acetaminophen overdoses, a portion of the drug is metabolized by CYP2E1 to form the potentially toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The amount of NAPQI produced in an overdose saturates and depletes glutathione stores. The free NAPQI promiscuously binds to proteins in hepatocytes, leading to cellular necrosis. Acetylcysteine can directly conjugate NAPQI or provide cysteine for glutathione production and NAPQI conjugation.

Ambroxol is a mucolytic agent. Excessive Nitric oxide (NO) is associated with inflammatory and some other disturbances of airways function. NO enhances the activation of soluble guanylate cyclase and cGMP accumulation. Ambroxol has been shown to inhibit the NO-dependent activation of soluble guanylate cyclase. It is also possible that the inhibition of NO-dependent activation of soluble guanylate cyclase can suppress the excessive mucus secretion, therefore it lowers the phlegm viscosity and improves the mucociliary transport of bronchial secretions.

Dosage

Rt O dosage

Acetylcysteine Tablet:

The dispersible tablet should be dissolved in 1/2 glass of water before use (preferably in the evening). The duration of treatment should be 5 to 10 days in the acute phase. It may be continued in the chronic state for up to 6 months or according to the advice of the physician.

As a mucolytic:

• Adults: 600 mg daily as a single dose.
• In Paracetamol overdose: Initially 140 mg/kg, followed by 70 mg/kg every 4 hours for an additional 17 doses. As an antidote, Acetylcysteine is reported to be very effective when administered within 8 hours of Paracetamol overdose, with the protective effect diminishing after this time. Initiation of treatment after a lapse of 15 hours has previously been thought to be ineffective, but recent studies suggest that beneficial results may still be obtained.

Acetylcysteine Respirator Solution:

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.

As a mucolytic:

Adult:

• 5-10 ml of 10% or 20% solution by nebulizer every 6-8 hr PRN.

Children:

• 1-11 months: 1-2 ml of 20% or 2-4 ml of 10% solution by nebulizer every 6-8 hr PRN.
• 12 months-11 years: 3-5 ml of 20% or 6-10 ml of 10% solution by nebulizer every 6-8 hr PRN.
• Below 12 years: 5-10 ml of 10/20% solution by nebulizer every 6-8 hr PRN.

Diagnostic Bronchograms: 1-2 ml of 20% or 2-4 ml of 10% solution 2-3 times by nebulization or by instillation intratracheally prior to procedure.

Nebulization tent or croupette: This form of administration requires very large volumes of the solution, occasionally as much as 300 ml during a single treatment period. If a tent or croupette must be used, the recommended dose is the volume of acetylcysteine (using 20%) that will maintain a very heavy mist in the tent or croupette for the desired period. Administration for intermittent or continuous prolonged periods, including overnight, may be desirable.

Direct Instillation: When used by direct instillation, 1-2 ml of a 20% solution may be given as often as every hour. When used for the routine nursing care of patients with tracheostomy, 1-2 ml of a 20% solution may be given every 1-4 hours by instillation into the tracheostomy.

Average daily dose (preferably after meal):Pediatric Drops:

• 0-6 months: 0.5 ml 2 times a day
• 6-12 months: 1 ml 2 times a day
• 1-2 years: 1.25 ml 2 times a day

Syrup:

• 2-5 years: 2.5 ml (1/2 teaspoonful) 2-3 times a day
• 5-10 years: 5 ml (1 teaspoonful) 2-3 times a day
• 10 years and adults: 10 ml (2 teaspoonful) 3 times a day.

Sustained release capsule:

• Adult and children over 12 years old: 1 capsule once daily

Specific application features: Ambroxol may be prescribed to patients suffering from diabetes mellitus.

Side Effects

Generally, Acetylcysteine is well tolerated. However, mild effects such as nausea, headache, tinnitus, urticaria, stomatitis, rhinorrhoea, chills, fever, bronchospasm may be observed. Occasional cases of nausea and dyspepsia, rare cases of urticaria may be observed.

Gastrointestinal side-effects like epigastric pain, gastric fullness may occur occasionally. Rarely allergic responses such as eruption, urticaria or angioneurotic edema may occur.

Toxicity

Patients experiencing an overdose may present with vomiting, nausea, bronchospasm, periorbital angioedema, and hypotension. Treat patients with symptomatic and supportive measures. Hemodialysis may remove some acetylcysteine from circulation as it is somewhat protein bound.

Precaution

Acetylcysteine should be given in caution in asthma patients.

Ambroxol should be given cautiously to patients with gastric and duodenal ulceration or convulsive disorders. Patients with hepatic and renal insufficiency should take it with caution.

Interaction

After taking Acetylcysteine orally it increases the bioavailability of Amoxicillin, but shows no effect on Doxycycline and reduces the absorption of Cefalexin. Acetylcysteine seems to increase the effects of Nitroglycerin.

Ambroxol has no interaction with cardioactive glycosides, corticosteroids, bronchodilators, diuretics and antibiotics (normally used in the treatment of bronchopulmonary affections). But Ambroxol should not be taken simultaneously with antitussives (e.g. Codeine) because mucus, which has been liquefied by Ambroxol, might not be expectorated.

Volume of Distribution

The volume of distribution of acetylcysteine is 0.47 L/kg.

Elimination Route

An 11 g dose in the form of an effervescent tablet for solution reaches a mean C_max of 26.5 µg/mL, with a T_max of 2 hours, and an AUC of 186 µg*h/mL.

Rapid and almost complete.

Half Life

The mean terminal half life of acetylcysteine in adults is 5.6 hours and in pre-term neonates is 11 hours.

7-12 hours

Clearance

Acetylcysteine has a mean clearance of 0.11 L/hr/kg.

Elimination Route

An oral dose of radiolabelled acetylcysteine is 13-38% recovered in the urine in the first 24 hours, while 3% is recovered in the feces.

Pregnancy & Breastfeeding use

Pregnancy Category B. Caution should be taken in case of pregnancy & lactation while using Acetylcysteine.

Pregnancy: Teratogenic and fetal toxicity studies have shown no harmful effect of Ambroxol. However, it is advised not to use during pregnancy, especially in the 1st trimester.

Lactation: Safety during lactation has not been established.

Contraindication

Known hypersensitivity to active ingredient. Also contraindicated in patients suffering from phenylketonuria and peptic ulcer.

Contraindicated in known hypersensitivity to Ambroxol or Bromhexine.

Acute Overdose

Accidental overdose of Acetylcysteine may cause nausea, vomiting or diarrhea.

Storage Condition

Protect from light & moisture, store below 25° C. Keep all medicines out of the reach of children.

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