Cofsonil

Uses

1. Expectorant in cough syrups.
2. The ammonium ion (NH4+) in the body plays an important role in the maintenance of acid-base balance. The kidney uses ammonium (NH4+) in place of sodium (Na+) to combine with fixed anions in maintaining acid-base balance, especially as a homeostatic compensatory mechanism in metabolic acidosis. The therapeutic effects of Ammonium Chloride depend upon the ability of the kidney to utilize ammonia in the excretion of an excess of fixed anions and the conversion of ammonia to urea by the liver, thereby liberating hydrogen (H+) and chloride (Cl–) ions into the extracellular fluid. Ammonium Chloride Injection, USP, after dilution in isotonic sodium chloride injection, may be indicated in the treatment of patients with: (1) hypochloremic states and (2) metabolic alkalosis.

Pseudoephedrine is a decongestant of the mucous membranes of the upper respiratory tract, especially the nasal mucosa, sinuses and eustachian tube. It is used for the symptomatic relief of allergic rhinitis (hay fever), vasomotor rhinitis, the common cold, influenza (flu) and ear congestion caused by ear inflammation or infection. Pseudoephedrine can also be used as a bronchodilator.

Pseudoephedrine is a stereoisomer of Ephedrine with similar but less potent pharmacological activity. It has nasal and bronchial decongestant activity.

Ipecac is an emetic agent used to induce vomiting in poisoning.

Ipecac is indicated as an emetic agent for the induction of vomiting in poisoning victims who ingested systemic poison in order to prevent absorption of the chemicals through the gastrointestinal tract. In low doses, ipecac was also used as an expectorant.

Reports have suggested that ipecac was vastly used in patients with eating disorders to produce vomiting.

Potassium bicarbonate is an ingredient used as an antacid or to treat hypokalemia.

Potassium bicarbonate is used as an antacid, electrolyte replenisher and potassium supplement. It can also be used as an excipient in drug formulations. An antacid is a medication used to neutralize gastric acid in a short timeframe after ingestion and the effect is soon overcome by meal-stimulated acid secretion.

Terpin hydrate is an expectorant used to treat bronchitis, pneumonia, bronchiectasis, COPD, and infectious or inflammatory diseases of the upper respiratory tract.

Terpin hydrate is used in the treatment of acute and chronic bronchitis, pneumonia, bronchiectasis, chronic obstructive pulmonary disease, infectious and inflammatory diseases of the upper respiratory tract.

Cofsonil is also used to associated treatment for these conditions: Allergic Reaction, Allergic cough, Common Cold, Cough, Cough caused by Common Cold, Diabetes, High Blood Pressure (Hypertension), Metabolic Alkalosis, Nasal Congestion, Nasal Congestion Due to Allergic Rhinitis, Productive cough, Rhinorrhoea, Sneezing, Bronchial congestion, Dry cough, Excess mucus or phlegm, Hypochloremic state, Airway secretion clearance therapy, Bronchodilation, Parenteral rehydration therapy, Weight Loss, PotassiumAllergic Disorder, Bronchial Asthma, Common Cold, Cough, Depression, Fever, General Anesthesia Induced Hypotension, Headache, Joint Pain, Myasthenia Gravis, Narcolepsy, Nasal Congestion, Rhinorrhoea, Sore Throat, Dry coughAllergic cough, Bronchitis, Cough, Cough caused by Common Cold, Rhinorrhoea, Sore Throat, Airway secretion clearance therapyArrhythmias Cardiac caused by Hypokalemia, Gastro-esophageal Reflux Disease (GERD), Hypocitraturia, Hypokalemia, Ketoacidosis caused by Hypokalemia, Kidney Stones, Neuromuscular Disorders caused by Hypokalemia, Uric Acid Stones, Calcium oxalate calculi Renal CalculiCough caused by Common Cold, Coughing caused by Bronchitis, Rhinorrhoea, Airway secretion clearance therapy

How Cofsonil works

Ammonium chloride increases acidity by increasing the amount of hydrogen ion concentrations.

Ammonium chloride can be used as an expectorant due to its irritative action on the bronchial mucosa. This effect causes the production of respiratory tract fluid which in order facilitates the effective cough.

Ephedrine is a direct and indirect sympathomimetic amine. Ephedrine activates adrenergic α and β-receptors as well as inhibiting norepinephrine reuptake, and increasing the release of norepinephrine from vesicles in nerve cells. These actions combined lead to larger quantities of norepinephrine present in the synapse, for longer periods of time, increasing stimulation of the sympathetic nervous system. Ephedrine's stimulation of α-1 receptors causes constriction of veins and a rise in blood pressure, stimulation of β-1 adrenergic receptors increase cardiac chronotropy and inotropy, stimulation of β-2 adrenergic receptors causes bronchodilation.

The emetic components of ipecac, emetine and cephaeline, act centrally and locally in the gastrointestinal tract to cause vomiting. The mechanism by which ipecac performs his effect is by irritating the stomach lining and chemically stimulating the chemoreceptor trigger zone.

The antacid potential of potassium bicarbonate is attained by increasing the gastrointestinal pH by neutralizing hydrochloric acid. The increase in pH results in suppression of the action of pepsin which is the enzyme that exacerbates ulceration due to the presence of acid.

Terpin hydrate improves mucociliary function by working directly on the bronchial secretory cells in the lower respiratory tract to liquify and facilitate the elimination of bronchial secretionsas well as exerting a weak antiseptic effect on the pulmonary parenchyma. It is thought to increase the amount of fluid in the respiratory tract, which increases the flow and clearance of local irritants and as well as reducing the viscosity of mucus .

Dosage

Cofsonil dosage

As a decongestant and symptomatic treatment for upper respiratory tract infections the recommended dose is:

Adults: 1 tablet every 4 to 6 hours, up to maximum of 240 mg in 24 hours

Children:

• 6-12 years of age: 1/2 tablet every 4 to 6 hours daily
• 2-5 years of age: 1/4 tablet every 4 to 6 hours daily
• Less than 2 years of age: This drug is not advised unless specifically recommended by a physician.

Side Effects

Serious adverse effects associated with the use of Pseudoephedrine are rare. Symptoms of central nervous system excitation may occur, including sleep disturbances and, rarely, hallucinations have been reported. Skin rashes, with or without irritation, have occasionally been reported.

Toxicity

LD50 "Rat" after oral administration is: 1650 mg/kg. Overdosage of Ammonium Chloride has resulted in a serious degree of metabolic acidosis, disorientation, confusion and coma. If metabolic acidosis occur following overdosage, the administration of an alkalinizing solution such as sodium bicarbonate or sodium lactate will serve to correct the acidosis.

Patients administering Ammonium chloride should be watched to the signs of ammonia toxicity including (pallor, sweating, irregular breathing, bradycardia, cardiac arrhythmias, local and general twitching, tonic convulsions and coma). It should be used with caution in patients with high total CO2 and buffer base secondary to primary respiratory acidosis. Intravenous administration should be slow to avoid local irritation and toxic effects.

Patients experiencing an overdose of ephedrine will present with rapidly increasing blood pressure. Manage overdose with blood pressure monitoring, and possibly the administration of parenteral antihypertensives. The LD₅₀ in mice after oral administration is 785mg/kg, after intraperitoneal administration if 248mg/kg, and after subcutaneous administration is 425mg/kg.

An overdose of an ipecac preparation may cause serious poisoning. If emesis is not provoked after two doses of ipecac, a gastric lavage is recommended. The overdose of the components such as emetine is reported to cause the onset of myopathy. Chronic use of this drug has been indicated to produce muscle weakness, waddling gait, dyspnea, left atrial enlargement and reduced left ventricular ejection fraction.

Potassium bicarbonate does not contain any toxic chemicals and it is not listed as a carcinogenic or a potential carcinogen. Potassium bicarbonate is also considered safe in pregnancy as the current data do not suggest a teratogenic potential or any developmental toxicity.

Overdose can cause nausea, vomiting and abdominal pain.

Precaution

Although Pseudoephedrine has virtually no pressor effects in normotensive patients, it should be used with caution in patients suffering mild to moderate hypertension. As with other sympathomimetic agents, Pseudoephedrine should be used with caution in patients with hypertension, heart disease, diabetes, hyperthyroidism, elevated intraocular pressure and prostatic enlargement. Caution should be exercised when using the product in the presence of severe hepatic impairment or moderate to severe renal impairment.

Volume of Distribution

Data not found.

Oral ephedrine has an average volume of distribution of 215.6L.

The volume of distribution is thought to be large based on the prolonged excretion.

Elimination Route

Completely absorbed within 3–6 h. In healthy persons, absorption of ammonium chloride given by mouth was practically complete. Only 1 to 3% of the dose was recovered in the feces.

Oral ephedrine reaches an average C_max of 79.5ng/mL, with a T_max of 1.81h, and a bioavailability of 88%.

The main components of ipecac are rapidly absorbed from the GI tract, this absorption depends on the amount of emesis produced by the administered dose. The peak plasma concentration of 10-16 ng/ml is attained 20 minutes after first administration. The bioavailability of ipecac is reduced over time from 67-11% after 5-60 minutes of administration.

Potassium bicarbonate intake is done mainly in the small intestine in which approximately 90% of the potassium will be absorbed by passive diffusion.

Half Life

Unknown

Oral ephedrine has a plasma elimination half life of approximately 6 hours, but there is a large degree of inter-patient variability.

The effect of ipecac is done in about 20 minutes and the elimination of the little-absorbed dose is reported to be very rapid. Thus, the half-life is thought to be of about 0.5-1 hour.

Some reports have shown that after absorption, most body potassium exchanges rapidly with a half-life of less than 7 hours.

Clearance

Data not found.

Oral ephedrine has a clearance of 23.3L/h but there is a high degree of inter-patient variability.

The urinary excretion of the main components of ipecac accounts for 75% of the administered dose 48 hours after initial administration.

Elimination Route

Excretion: Urine

Ephedrine is mainly eliminated in the urine. Approximately 60% is eliminated as the unmetabolized parent compound, 13% as benzoic acid conjugates, and 1% as 1,2-dihydroxypropylbenzene.

Due to the emetic function, even 76% of the administered dose is vomited. From the absorbed dose, the elimination from plasma is relatively rapid. In some clinical trials, the alkaloids were not observed in plasma 6 hours after administration. When the patient does not vomit any part of the administered dose, there could be traces in plasma after 24 hours. The component alkaloids are eliminated via the bile and urine as it has been observed a persistence in urine after chronic administration. Biliary and urinary excretion of ipecac corresponds to 57.5% and 16.5% of the administered dose respectively. From the excreted dose, unchanged cephaeline accountd for 42.4% of the eliminated dose in feces.

Approximately 90% of the exogenous potassium consumed is lost in the urine while the other 10% is excreted in feces and a very small amount can be found in the sweat. The excreted potassium is freely filtered by the glomerulus of the kidney.

Pregnancy & Breastfeeding use

Although Pseudoephedrine has been in widespread use for many years without apparent ill consequence, there are no specific data on its use during pregnancy. Caution should therefore be exercised by balancing the potential benefit of treatment to the mother against any possible hazards to the developing foetus. Pseudoephedrine is excreted in breast milk in small amounts but the effect of this on breast-fed infants is not known.

Contraindication

Pseudoephedrine is contraindicated in-

• Hypersensitivity of individuals to this drug
• Severe hypertension and coronary artery disease
• Concurrent use of Mono Amine Oxidase Inhibitor (MAOI) drugs

Acute Overdose

As with other sympathomimetic agents, symptoms of overdosage include irritability, restlessness, tremor, convulsions, palpitations, hypertension and difficulty in micturition. Necessary measures should be taken to maintain and support respiration and control convulsions. Gastric lavage should be performed if indicated. If desired, the elimination of Pseudoephedrine can be accelerated by acid diuresis or by dialysis.

Innovators Monograph

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