Pexol

Uses

It is used for the treatment and prophylaxis of bronchospasm associated with asthma, emphysema and chronic bronchitis. Also used for adults for the treatment of cardiac asthma and left ventricular or congestive cardiac failure.

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.

Pexol is also used to associated treatment for these conditions: Acute Exacerbation of Chronic Bronchitis (AECB), Asthma, Bronchial Asthma, Bronchospasm, Chronic Bronchitis, Exacerbation of asthmaAllergic 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 cough

How Pexol works

Aminophylline is the ethylenediamine salt of theophylline. After ingestion, theophylline is released from aminophylline, and theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.

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.

Dosage

Pexol dosage

Oral:Chronic bronchospasm:

• Adult: As hydrate: Initially, 225-450 mg bid, increased if necessary.
• Child: >3 yr: As modified-release hydrate: 12 mg/kg daily increased to 24 mg/kg daily in 2 divided doses after 1 wk.

Intravenous:Acute severe bronchospasm:

• Adult: Loading dose: 5 mg/kg (ideal body weight) or 250-500 mg (25 mg/ml) by slow inj or infusion over 20-30 min. Maintenance infusion dose: 0.5 mg/kg/hr. Max rate: 25 mg/min.
• Child: Loading dose: same as adult dose. Maintenance dose: 6 mth-9 yr: 1 mg/kg/hr and 10-16 yr: 0.8 mg/kg/hr.
• Elderly: Dose reduction may be necessary.
• Hepatic impairment: Dose reduction may be necessary.

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.

Tablets should be swallowed whole and not chewed because of the structure of the tablet.

Side Effects

The most common adverse effects are gastric irritation, nausea, vomiting, diarrhea, hematemesis, epigastric pain and tremor. These are usually early signs of toxicity; however, with high doses, ventricular arrhythmias or seizures may be the first signs to appear and reactivation of peptic ulcer, headache, irritability, restlessness, insomnia, twitching, convulsion and reflex hyperexcitability, palpitation, tachycardia, hypotension, circulatory failure, ventricular arrhythmias, and flushing, albuminuria, diuresis and hematuria. Also inappropriate ADH syndrome may occur.

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.

Precaution

Aminophylline should be given with caution to patients with peptic ulceration, hyperthyroidism, hypertension, cardiac arrhythmias or other cardiovascular disease, or epilepsy, as these conditions may be exacerbated. They should also be given withcaution to patients with heart failure, hepatic dysfunction, chronic alcoholism, acute febrile illness, and to neonates and the elderly, since in all of these circumstances theophylline clearance may be decreased, resulting in increases in serum-theophylline concentrations and serum half-life.

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

• 0.3 to 0.7 L/kg

Data not found.

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

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%.

Half Life

7-9 hours

Unknown

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

Clearance

• 0.29 mL/kg/min [postnatal age 3-15 days]
• 0.64 mL/kg/min [postnatal age 25-57 days]
• 1.7 mL/kg/min [ 1-4 years]
• 1.6 mL/kg/min [4-12 years]
• 0.9 mL/kg/min [13-15 years]
• 1.4 mL/kg/min [16-17 years]
• 0.65 mL/kg/min [Adults (16-60 years), non-smoking asthmatics]
• 0.41 mL/kg/min [Elderly (>60 years). liver, and renal function]
• 0.33 mL/kg/min [Acute pulmonary edema]
• 0.54 mL/kg/min [COPD->60 years, stable non-smoker >1 year]
• 0.48 mL/kg/min [COPD with cor pulmonale]
• 1.25 mL/kg/min [Cystic fibrosis (14-28 years)]
• 0.31 mL/kg/min [Liver disease -cholestasis]
• 0.35 mL/kg/min [cirrhosis]
• 0.65 mL/kg/min [acute hepatitis]
• 0.47 mL/kg/min [Sepsis with multi-organ failure]
• 0.38 mL/kg/min [hypothyroid]
• 0.8 mL/kg/min [hyperthyroid]

Data not found.

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

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.

Pregnancy & Breastfeeding use

Use of aminophylline in pregnant women should be balanced against the risk of uncontrolled disease.

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

Aminophylline should not be administered to patients with hypersensitivity to xanthines or ehylenediamine. It should not be administered to patients with active peptic ulcer, since it may increase the volume and acidity of gastric secretions.

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.

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