Phencodin

Uses

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.

Pholcodine is used for a cough suppressant for the temporary relief of non-productive dry cough. It is stated to present a required label indication of "temporary relief of dry cough". Cough is the respiratory movement that occurs after an irritation signal is transmitted to the central nervous system and further stimulates the medulla oblongata. This stimulation causes a motor output that is sent through motoneurons to the respiratory muscles. A non-productive cough is a type of cough characterized by the absence of sputum, and it has a large inspiration that will cause continuous coughing.

Phencodin is also used to associated treatment for these conditions: Allergic Disorder, Bronchial Asthma, Common Cold, Cough, Depression, Fever, General Anesthesia Induced Hypotension, Headache, Joint Pain, Myasthenia Gravis, Narcolepsy, Nasal Congestion, Rhinorrhoea, Sore Throat, Dry coughCough, Cough caused by Common Cold, Flu Like Symptom, Flu caused by Influenza, Irritative cough, Rhinorrhoea, Sinusitis, Sneezing, Throat irritation, Dry cough, Watery eyes

How Phencodin works

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 mechanism of action of pholcodine is directly performed in the medulla oblongata. In this site, it exerts analgesic properties on the peripheric reflexogenic receptors. This site is commonly known as the "cough center."

Dosage

Phencodin 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.

Adult:

• Symptomatic relief of non-productive cough: 5-10 mg 3-4 times daily.

Child:

• 12-18 year: 5-10 mg 3-4 times daily.
• 6-12 year: 2-5 mg 3-4 times daily.
• Children under the age of 6 year:Not to be used

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.

Dizziness, occasional drowsiness, nausea, vomiting, constipation, rash, sputum retention, excitation, confusion, ataxia.

Toxicity

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.

Generally, pholcodine is significantly less toxic than codeine. Nonetheless, it is important to consider the significant depressive respiratory effect.

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.

Renal and/or hepatic impairment. Caution in patients with impaired respiratory function and asthma. May cause occasional drowsiness, caution when driving or operating machinery. Pregnancy and lactation.

Interaction

Not to be used with MAOI or within 14 days of stopping treatment. May enhance sedative effect of alcohol and other CNS depressants e.g. sedatives, hypnotics, barbiturates, narcotic analgesics, phenothiazines, tricyclic antidepressants. Hypotensive effect may be enhanced when used with antihypertensive agents and diuretics. Interaction with neuromuscular blocking agent has been reported.

Volume of Distribution

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

The reported volume of distribution depends on the pharmacokinetic model and it can be of 265L based on a one-compartment model to 3207L in a two-compartment model.

Elimination Route

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

After oral administration of 60 mg of pholcodine, the Tmax and Cmax are reported to be 1.3 hours and 26.3 ng/ml. In the same administration, the AUC in plasma and saliva are reported to be 1.67 and 6.61 mg h/l respectively. The absorption of pholcodine is reported to represent approximately 88% of the administered dose.

Half Life

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

After oral administration of 60 mg of pholcodine, the half-life in plasma, saliva and urine are 45, 55 and 45 hours respectively.

Clearance

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

After oral administration of 60 mg of pholcodine, the clearance rate was reported to be 126 ml/min.

Elimination Route

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.

After oral administration of pholcodine, the serum concentration peaks and declines in a monoexponential manner. The percent of the dose excreted unchanged is of approximately 25-30%. Part of the administered dose is composed by metabolites that can be recovered in urine. From the administered dose, the fecal excretion corresponds to the 5% of the administered dose as unchanged pholcodine.

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.

Category not classified

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

Patients in, or at risk of developing respiratory failure. Chronic bronchitis, COPD, bronchiolitis, and bronchiectasis due to sputum retention. Concurrent or recent use (within preedicing 14 days) of MAOIs. Children <6 yr

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.

Symptoms: Drowsiness, nausea, restlessness, excitement, ataxia and respiratory depression.

Management: Provide symptomatic and supportive treatment. Maintain respiration; may use activated charcoal or gastric lavage to remove the ingested Pholcodine. In cases of severe overdosage, naloxone may be given to reverse the central and peripheral opioid effects.

Storage Condition

Store below 25° C.

Innovators Monograph

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