Antigrippin

Antigrippin is a combination drug intended for the symptomatic treatment of colds and flu. It contains three active ingredients: paracetamol, chlorphenamine maleate and ascorbic acid. Each of these components has its own specific action, which together provides comprehensive treatment.

1. Paracetamol:

   • Action: Has analgesic and antipyretic properties. Helps reduce pain and fever.
   • Mechanism: Blocks the synthesis of prostaglandins in the central nervous system, which reduces pain and lowers body temperature.

2. Chlorphenamine maleate:

   • Action: Antihistamine that eliminates allergy symptoms such as runny nose, lacrimation, itching.
   • Mechanism: Blocks histamine H1 receptors, which reduces the occurrence of allergic reactions.

3. Ascorbic acid (vitamin C):

   • Action: Strengthens the immune system, increases the body's resistance to infections, improves tissue regeneration.
   • Mechanism: Participates in redox processes, collagen synthesis, carbohydrate and lipid metabolism.

Indications Antigrippina

Antigrippin is used to relieve cold and flu symptoms such as:

• Headaches.
• Fever.
• Runny nose.
• Muscle and joint pain.
• Sneezing and watery eyes.

Release form

1. Effervescent tablets:
   • Tablets that dissolve in water to produce a drink.
   • Convenient for quick and effective absorption of active components.
2. Powder for preparing the solution:
   • Powder that is dissolved in water to produce a drink.
   • Also provides rapid absorption and relief of symptoms.

Pharmacodynamics

Paracetamol

• Mechanism of action: Paracetamol has an analgesic (pain-relieving) and antipyretic effect, blocking the synthesis of prostaglandins in the central nervous system (CNS). It inhibits the enzyme cyclooxygenase (COX), which leads to a decrease in the formation of prostaglandins, which are responsible for pain and inflammation.
• Effects: Reducing body temperature and relieving pain from colds and flu.

Chlorphenamine maleate

• Mechanism of action: Chlorphenamine is an antihistamine that blocks histamine H1 receptors. This prevents the action of histamine, which is a mediator of allergic reactions.
• Effects: Reduction of allergy symptoms such as runny nose, sneezing, itchy nose and eyes, watery eyes. Chlorphenamine also has a mild sedative effect, which may help improve sleep during colds.

Ascorbic acid (vitamin C)

• Mechanism of action: Ascorbic acid is involved in numerous metabolic processes. It is an important antioxidant that protects cells from free radical damage. It also plays a key role in collagen synthesis, increasing the strength and integrity of vascular walls and tissues.
• Effects: Strengthening the immune system, increasing the body's resistance to infections, accelerating the processes of healing and tissue restoration.

Synergetic effect

The combination of these three components allows Antigrippin to effectively combat a wide range of cold and flu symptoms. Paracetamol reduces pain and fever, chlorphenamine reduces allergic symptoms and improves overall well-being, and ascorbic acid supports the immune system and speeds up recovery.

This multi-component approach can alleviate the patient’s condition and promote faster recovery from colds and flu.

Pharmacokinetics

Paracetamol

• Absorption: Paracetamol is quickly and completely absorbed from the gastrointestinal tract. Maximum plasma concentration is achieved 0.5-2 hours after administration.
• Distribution: Distributed evenly throughout tissues, penetrates the placental barrier, and enters breast milk. The binding to plasma proteins is low - about 10-25%.
• Metabolism: Metabolized in the liver by conjugation with glucuronic and sulfuric acids. Less than 5% of the dose undergoes hydroxylation to form an active metabolite, which is then conjugated to glutathione.
• Excretion: Excreted by the kidneys, mainly in the form of metabolites; about 3% is excreted unchanged. The half-life is 1-4 hours.

Chlorphenamine maleate

• Absorption: Chlorphenamine is rapidly absorbed from the gastrointestinal tract, reaching maximum plasma concentrations after 2-6 hours.
• Distribution: Penetrates well into tissues, including the central nervous system. The binding to plasma proteins is about 70%.
• Metabolism: Metabolized in the liver by demethylation and oxidation. The main metabolites are desmethylchlorphenamine and dihydroxychlorphenamine.
• Excretion: Excreted by the kidneys in the form of metabolites and unchanged. The half-life is 12-15 hours.

Ascorbic acid

• Absorption: Ascorbic acid is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentration is achieved after 2-3 hours.
• Distribution: Distributed throughout all tissues of the body, with high concentrations in the endocrine glands, liver, leukocytes and the lens of the eye. Plasma protein binding is about 25%.
• Metabolism: Metabolized in the liver to dihydroascorbic acid and other metabolites.
• Excretion: Excreted by the kidneys, both unchanged and in the form of metabolites. The half-life is about 16 days at high dosages and 3-4 hours at normal doses.

Combined action

The combination of paracetamol, chlorphenamine and ascorbic acid in Antigrippin provides quick and effective relief from cold and flu symptoms. Each of the substances complements the action of each other, helping to improve the patient’s general condition and speed up the healing process.

Dosing and administration

Tablets:

• Adults and children over 15 years of age: 1 tablet every 4-6 hours as needed. The maximum daily dose is 4 grams (8 tablets).
• Children from 10 to 15 years: ½-1 tablet every 6-8 hours as needed. The maximum daily dose is 2 grams (4 tablets).
• Children from 5 to 10 years: ½ tablet every 6-8 hours as needed. The maximum daily dose is 1 gram (2 tablets).
• Children from 3 to 5 years: ¼-½ tablet every 6-8 hours as needed. The maximum daily dose is 500 mg (1 tablet).

Powder for preparing the solution:

• Adults and children over 15 years old: 1-2 sachets 2-3 times a day.
• Children from 10 to 15 years: 1 sachet 2-3 times a day.
• Children from 5 to 10 years: ½-1 sachet 2-3 times a day.
• Children from 3 to 5 years: ½ sachet 2-3 times a day.

Liquid form (syrup):

The dosage of syrup is usually indicated in milliliters, not milligrams. Follow package directions or your doctor's instructions to determine the correct dosage in milliliters based on your child's age or adult recommendations.

Topical spray:

• Adults and children over 12 years of age: 1-2 sprays in each nostril 3-4 times a day.
• Children from 6 to 12 years old: 1 spray in each nostril 3-4 times a day.
• Children from 3 to 6 years: 1 spray in each nostril 1-2 times a day.

Use Antigrippina during pregnancy

1. Paracetamol (acetaminophen):

   • Paracetamol is widely used to treat pain and fever in pregnant women. Research shows that it is considered relatively safe when taken at recommended doses. However, some studies have linked long-term paracetamol use during pregnancy to an increased risk of behavioral and neurodevelopmental disorders in children, such as ADHD and autism spectrum disorder (Liew et al., 2014), (Thiele et al., 2015).

2. Chlorphenamine maleate:

   • Chlorphenamine is an antihistamine used to reduce allergy and cold symptoms. Although there is limited data on its safety in pregnancy, it is usually used in small doses and is considered relatively safe for short-term use. However, the use of antihistamines in the first trimester requires caution due to possible risks to the fetus (Sun et al., 2006).

3. Ascorbic acid:

   • Ascorbic acid (vitamin C) is safe to use during pregnancy at recommended doses. It is important for maintaining the health of the immune system and does not pose a threat to the fetus (Garmonov & Salakhov, 2009).

Contraindications

General contraindications for all components

1. Hypersensitivity to any of the components of the drug.
2. Age up to 15 years (for adult forms of release) or up to 12 years (for children's forms), unless otherwise specified in the instructions.

Contraindications associated with paracetamol

1. Severe liver diseases (including acute liver failure).
2. Severe renal failure.
3. Congenital hyperbilirubinemia (Gilbert, Dabin-Johnson syndromes, etc.).
4. Alcoholism.
5. Glucose-6-phosphate dehydrogenase deficiency.

Contraindications associated with chlorphenamine maleate

1. Angle-closure glaucoma.
2. Prostatic hypertrophy with urinary retention.
3. Severe cardiovascular diseases.
4. Peptic ulcer of the stomach and duodenum in the acute stage.

Contraindications associated with ascorbic acid

1. Hyperoxaluria (increased excretion of oxalates in the urine).
2. Severe kidney disease.
3. Thrombophlebitis and tendency to thrombosis.
4. Glucose-6-phosphate dehydrogenase deficiency (can lead to hemolytic anemia).

Additional contraindications

1. Pregnancy and lactation: The drug is not recommended for use without consulting a doctor, since the safety of use during these periods has not been established.
2. Diabetes mellitus: Since the drug may contain sugar or other sweeteners, this factor must be taken into account when used in patients with diabetes mellitus.

Side effects Antigrippina

Common side effects:

1. Drowsiness or dizziness: Especially often observed when using formulas containing chlorphenamine maleate.
2. Dry mouth: Due to the anticholinergic properties of chlorphenamine.
3. Stomach disorders: May include nausea, vomiting, diarrhea, or indigestion.
4. Allergic reactions: May include skin rash, itching, hives, or swelling of the face, lips, tongue, and throat.

Acetaminophen-related:

1. Liver damage: If the recommended dose of paracetamol is exceeded, hepatotoxicity, including acute liver failure, may occur.
2. Allergic reactions: May include hives, itching, skin rash, or angioedema.

Chlorphenamine maleate-related:

1. Drowsiness and decreased alertness: These effects may result in impaired coordination and impaired reaction time.
2. Urethral stenosis: May worsen urinary conditions in men with prostatic hypertrophy.

Ascorbic acid-related:

1. Stomach disorders: May include nausea, vomiting, heartburn, or diarrhea, especially with high doses.
2. Kidney stones: Long-term and/or excessive use of vitamin C may increase the risk of kidney stones in some people.

Overdose

1. Symptoms of paracetamol:

   • Nausea.
   • Vomiting.
   • Stomach pain.
   • Loss of appetite.
   • Drowsiness or weakness.
   • Increased activity of liver enzymes in the blood (according to test results).
   • Liver damage, including acute liver failure (in severe cases).

2. Symptoms of chlorphenamine maleate:

   • Drowsiness.
   • Blurred vision.
   • Dry mouth.
   • Lower blood pressure.
   • Tachycardia (increased heart rate).

3. Symptoms of ascorbic acid:

   • Increased acidity of gastric juice.
   • Diarrhea.
   • Risk of kidney stones (with long-term and/or excessive use).

Interactions with other drugs

1. Medicines containing paracetamol:

   • The simultaneous use of several drugs containing paracetamol can lead to overdose and liver damage.
   • This is especially important to consider when taking medications for pain, headaches, or antipyretics at the same time.

2. Drugs that have hepatotoxic effects:

   • Concomitant use of Antigrippin with other drugs that can damage the liver may increase the risk of developing hepatotoxic effects.
   • These drugs may include some antibiotics, antivirals, and seizure medications.

3. Drugs that have a sedative effect:

   • Antigrippin contains chlorphenamine, which has a sedative effect. Concomitant use with other drugs that also have a sedative effect (for example, hypnotics, sedatives, antidepressants) may enhance this effect and lead to increased drowsiness and lethargy.

4. Drugs that have anticholinergic effects:

   • Chlorphenamine maleate contained in Antigrippin has anticholinergic properties. Concomitant use with other drugs with anticholinergic effects (eg, pain medications, antihistamines) may increase these effects, such as dry mouth, constipation, and urinary retention.

5. Drugs that affect the circulatory system:

   • Chlorphenamine maleate may enhance the hypotensive effect of antihypertensive drugs, as well as enhance tachycardia caused by sympathomimetic amines.

6. Preparations containing vitamin C:

   • Long-term and/or excessive use of medications containing vitamin C together with Antigrippin may increase the risk of kidney stones.