Acetylcysteine

Acetylcysteine is a medicinal substance that is a derivative of the amino acid cysteine. It is often used in medicine as a mucolytic agent, that is, a drug that liquefies and improves expectoration of sputum.

The drug is used to treat various respiratory diseases such as bronchitis, chronic obstructive pulmonary disease (COPD), bronchial asthma, cystic fibrosis and others.

Acetylcysteine works by breaking disulfide bonds in mucoproteins of sputum, which leads to its liquefaction and improvement of expectoration. The drug also has antioxidant properties, protecting the lungs from free radical damage.

Indications Acetylcysteine

1. Chronic and exacerbated bronchitis: Acetylcysteine helps to soften sputum and improve its expectoration in exacerbations or in the chronic course of bronchitis.
2. Chronic obstructive pulmonary disease (COPD): Acetylcysteine may be prescribed to patients with COPD to help them breathe easier by thinning sputum and reducing its viscosity.
3. Bronchial asthma: The drug can be used in the complex therapy of bronchial asthma to relieve inflammation of the respiratory tract and facilitate expectoration.
4. Cystic Fibrosis: In patients with cystic fibrosis, acetylcysteine may help reduce sputum viscosity and improve expectoration.
5. Pneumonia: In cases of pneumonia, the drug may be prescribed to facilitate expectoration and speed recovery.
6. Prevention of recurrent respiratory disease: Acetylcysteine may be used to prevent recurrences of bronchitis and other respiratory diseases in patients who are prone to them.

Release form

1. Oral forms:

   • Tablets or capsules: Often used to treat chronic respiratory diseases and as an adjunct to therapy to improve antioxidant defense.
   • Fizzy tablets: Dissolved in water and consumed in the form of a solution, which is convenient for dosage adjustment and improving the taste of the drug.

2. Injectable forms:

   • Solutions for injection or infusion: Used in hospital settings, especially for urgent treatment of severe conditions such as paracetamol intoxication where a rapid effect is needed.

3. Inhalation forms:

   • Inhalation solutions: Used through a nebulizer to treat respiratory diseases such as chronic obstructive pulmonary disease (COPD) or cystic fibrosis by facilitating the expulsion of sputum from the airways.

4. Liquid forms for oral administration:

   • Syrups or solutions: Can be used for children and adults who have difficulty swallowing tablets.

Pharmacodynamics

1. Mucolytic action:

   • The main pharmacodynamic action of acetylcysteine lies in its ability to break disulfide bonds in sputum-forming mucopolysaccharides.
   • By breaking these bonds, acetylcysteine improves sputum expectoration in patients with acute and chronic bronchopulmonary pathologies such as bronchitis, bronchiectasis, chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis.

2. Antioxidant action:

   • Acetylcysteine has antioxidant properties due to the presence of thiol group in its structure.
   • It is able to neutralize free radicals such as hydrogen peroxide and hydroxyl radicals, preventing oxidative stress and cell damage.

3. Anti-inflammatory action:

   • Acetylcysteine may have anti-inflammatory effects by reducing the concentration of cytokines and other inflammatory mediators.
   • This action helps to reduce inflammation in the airways and reduce associated symptoms such as coughing and difficulty breathing.

4. Protection from lung damage:

   • Acetylcysteine may also protect the lungs from damage caused by various factors such as infections, smoking, air pollution and toxic substances.
   • This drug may reduce inflammation and oxidative stress in the lungs, promoting lung repair and improving respiratory function.

Pharmacokinetics

1. Absorption: After oral administration of acetylcysteine it is rapidly absorbed from the gastrointestinal tract. Peak blood concentrations are usually reached 1-2 hours after ingestion.
2. Distribution: Acetylcysteine has a large volume of distribution, which means that it is widely distributed throughout the tissues of the body. It penetrates the blood-brain barrier and can reach high concentrations in the central nervous system.
3. Metabolism: Acetylcysteine undergoes minimal metabolism in the body. It is predominantly metabolized in the liver to cysteine, which can then be used to synthesize glutathione, a key antioxidant in the body.
4. Excretion: Acetylcysteine and its metabolites are eliminated from the body mainly through the kidneys. Most of the dose is excreted as metabolites and cysteine in the urine.
5. Half-life: Half-life of acetylcysteine from the body is about 6-14 hours. In case of renal dysfunction this time may increase.
6. Individual characteristics: The pharmacokinetics of acetylcysteine may be altered in patients with impaired renal or hepatic function.
7. Long-lasting effects: After taking acetylcysteine, there is a long-lasting effect due to its ability to increase glutathione levels in the body, which helps in fighting oxidative stress.

Dosing and administration

For the treatment of respiratory diseases

1. Oral administration:

   • Adults and adolescents over 14 years of age: The usual dose is 200 mg (usually in effervescent tablet or powder form) three times daily or 600 mg once daily in the prolonged-acting form.
   • Children 6 to 14 years of age: 200 mg two or three times daily.
   • Children from 2 to 6 years of age: 100 mg two or three times a day.

2. Inhalations:

   • Adults and children: Dosage for inhalation may vary, but a typical dose is 3-5 mL of 20% solution or 6-10 mL of 10% solution twice daily.

3. Intranasal application:

   • To thin nasal secretions: Use acetylcysteine solution, a few drops in each nasal passage.

To treat paracetamol poisoning

• Intravenous administration:
  • Start treatment immediately if significant poisoning is suspected.
  • The usual regimen includes an initial dose of 150 mg/kg body weight in 200 mL of 5% dextrose administered over 15 minutes, followed by 50 mg/kg in 500 mL of 5% dextrose administered over the next 4 hours, and a final dose of 100 mg/kg in 1000 mL of 5% dextrose administered over the next 16 hours.

General recommendations

• Acetylcysteine may cause gastrointestinal irritation, so it should be taken after meals to reduce gastric discomfort.
• The effervescent tablets should be dissolved completely in water before use.
• Always follow the exact dosage and regimen recommended by your doctor.

Use Acetylcysteine during pregnancy

Acetylcysteine has no rigorous clinical data on the safety of its use during pregnancy, but preliminary data indicate that it has no teratogenic (causing malformations) effects in animals. In the absence of clear safety evidence:

1. First trimester: In the first three months of pregnancy, the use of acetylcysteine is recommended only if absolutely necessary and only if the expected benefit to the mother exceeds the potential risk to the fetus. This is because the first trimester is a critical period for the development of all major organs of the fetus.

2. Second and third trimesters: The use of acetylcysteine may be safer in the second and third trimesters, but still requires caution and medical supervision. An assessment of the risk-benefit ratio should be made.

Medical supervision

If a pregnant woman needs to use acetylcysteine, it should be done under strict medical supervision. Doctors should monitor the condition of both mother and fetus to detect any possible adverse reactions in time.

Contraindications

1. Individual intoleranceor allergy: People with known individual intolerance to acetylcysteine or any other component of the drug should avoid its use.
2. Pepticulcer disease of the stomach and duodenum: The drug may increase irritation of gastric and intestinal mucosa, therefore its use may be contraindicated in peptic ulcer disease.
3. Bleeding: Acetylcysteine may increase the risk of bleeding and should therefore be used with caution in patients with clotting disorders or taking anticoagulants.
4. Pregnancy and lactation: Safety of acetylcysteine use during pregnancy and lactation has not been established. Therefore, its use should be coordinated with a physician.
5. Bronchialasthma with periods of exacerbations: The use of acetylcysteine may increase bronchial spasms in patients with bronchial asthma, especially during exacerbations.
6. Hepatic insufficiency: In the presence of serious liver disease, dosage adjustment or complete withdrawal from the drug may be required.
7. Pediatric age: The safety and efficacy of acetylcysteine in children younger than 2 years of age have not been established.

Side effects Acetylcysteine

1. Anaphylactoid reactions: The most common reactions to intravenous administration of acetylcysteine include skin rashes, pruritus, angioedema, bronchospasm and rarely hypotension. These reactions are due to non-immunologic mechanisms and often occur at the beginning of treatment when blood concentrations of the drug are highest (Sandilands & Bateman, 2009).
2. Gastrointestinal disturbances: Common side effects include nausea, vomiting and diarrhea. These symptoms are more commonly associated with oral administration of acetylcysteine, especially at high doses (Chyka et al., 2000).
3. Effect on blood coagulation: Acetylcysteine may affect blood coagulation parameters, which is important when interpreting tests in patients with paracetamol overdose but without evidence of liver damage (Schmidt et al., 2002).
4. Interaction with other drugs: Acetylcysteine may interact with other drugs, including those that affect oxidative stress and drug metabolism, which requires special attention in combination therapy.

Overdose

1. Gastrointestinal disorders: Nausea, vomiting, diarrhea, stomach pain and discomfort may occur.
2. Serious allergic reactions: In rare cases, allergic reactions such as urticaria, pruritus, laryngeal edema, anaphylaxis may occur.
3. Irritationof respiratory mucosa: Irritation and inflammation of respiratory mucosa may occur with inhalation or ingestion of large doses of acetylcysteine.
4. Increased blood cysteine levels:Blood cysteine levels may be elevated, which may lead to additional problems, especially in patients with kidney disorders or genetic diseases related to amino acid metabolism.

Interactions with other drugs

1. Paracetamol (acetaminophen): Combining acetylcysteine with paracetamol may enhance its hepatoprotective effect and help prevent liver damage associated with paracetamol overdose.
2. Nitroglycerin: Acetylcysteine may reduce the efficacy of nitroglycerin in the treatment of angina pectoris because the hepatoprotective effect of acetylcysteine may reduce nitric oxide formation.
3. Drugs containing tetracyclines and aminoglycosides: Acetylcysteine may interact with these antibiotics and reduce their absorption from the gastrointestinal tract.
4. Heparin: Interaction of acetylcysteine with heparin may result in increased anticoagulant effect of heparin.
5. Carbamazepine: Acetylcysteine may decrease carbamazepine concentration in blood due to acceleration of its metabolism in liver.
6. Preparations containing activated charcoal: The combination of acetylcysteine with activated charcoal may reduce its hepatoprotective effect.
7. Drugs containing nitrofurans: Acetylcysteine may increase the toxicity of nitrofuran antibiotics by increasing their concentration in the liver.
8. Drugs affecting renal function: Interaction with drugs affecting renal function may lead to changes in the pharmacokinetics of acetylcysteine.