Ashreliv

Uses

Indicated mainly in allergic conditions including urticaria, sensitivity reactions, angioneurotic oedema, seasonal hay fever, vasomotor rhinitis, cough, common cold, motion sickness.

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.

This is used for the symptomatic treatment of reversible bronchoconstriction associated with bronchial asthma, chronic obstructive pulmonary emphysema, chronic bronchitis and related bronchospastic disorders.

Ashreliv is also used to associated treatment for these conditions: Allergic Contact Dermatitis, Allergic Reaction, Allergic Rhinitis (AR), Allergic cough, Allergies, Allergies caused by Serum, Allergy to House Dust, Allergy to vaccine, Angioneurotic Edema, Asthma, Bronchial Asthma, Bronchitis, Common Cold, Conjunctival congestion, Conjunctivitis, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Coughing caused by Flu caused by Influenza, Drug Allergy, Eye allergy, Fever, Flu caused by Influenza, Food Allergy, Headache, Headache caused by Allergies, Itching of the nose, Itching of the throat, Migraine, Nasal Congestion, Nasal Congestion caused by Common Cold, Pollen Allergy, Productive cough, Pruritus, Rash, Rhinorrhoea, Seasonal Allergic Conjunctivitis, Sinus Congestion, Sinusitis, Sneezing, Transfusion Reactions, Upper Respiratory Tract Infection, Upper respiratory tract hypersensitivity reaction, site unspecified, Urticaria, Vasomotor Rhinitis, Acute Rhinitis, Allergic purpura, Conjunctival hyperemia, Dry cough, Excess mucus or phlegm, Itchy throat, Mild bacterial upper respiratory tract infections, Ocular hyperemia, Throat inflammation, Upper airway congestion, Upper respiratory symptoms, Watery eyes, Watery itchy eyes, Airway secretion clearance therapyAllergic Disorder, Bronchial Asthma, Common Cold, Cough, Depression, Fever, General Anesthesia Induced Hypotension, Headache, Joint Pain, Myasthenia Gravis, Narcolepsy, Nasal Congestion, Rhinorrhoea, Sore Throat, Dry coughAsthma, Bronchitis, Bronchoconstriction, Bronchospasm, Chronic Obstructive Pulmonary Disease (COPD), Chronic bronchial inflammation, Airway secretion clearance therapy, Bronchodilation

How Ashreliv works

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

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.

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.

Dosage

Ashreliv dosage

Adults: 4 mg 3-4 times daily.

Children:

• Up to 1( one) year: 1 mg twice daily
• 1-5 years: 1 mg 3-4 times daily
• 6-12 years: 2 mg 3-4 times daily or as directed by the physician

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.

Dosages are adjusted to maintain serum theophylline concentrations that provide optimal relief of symptoms with minimal side effects. Most of the controlled release preparations may be administered every 12 hours in adults while administration every 8 hours may be necessary in some children with markedly rapid hepatic metabolism of theophylline. The recommended dosages for achieving serum theophylline concentrations within the accepted therapeutic range is as follow:

• 1-6 months: 10mg/Kg/day
• 6 months-1 year: 15mg/Kg/day
• 1-9 years: 24mg/Kg/day
• 10-16 years: 18mg/Kg/day
• Adults: 10-15mg/Kg/day

Side Effects

Drowsiness, dizziness, headache, psychomotor impairment, urinary retention, dry mouth, blurred vision and gastro intestinal disturbances, paradoxical stimulation may rarely occur, especially in high dosage or in children.

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.

The following side effects have been observed:

Gastrointestinal: Nausea, vomiting, epigastric pain and diarrhoea.

Central nervous system: Headache, irritability, restlessness, insomnia, muscles twitching.

Cardiovascular: Palpitation, tachycardia, hypotension. circulatory failure.

Respiratory: Tachypnoea.Renal: Potentiation of diuresis.

Others: Alopecia, hyperglycemia, rash etc.

Toxicity

Oral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.

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.

Symptoms of overdose include seizures, arrhythmias, and GI effects.

Precaution

Chlorpheniramine may produce mild sedation and it is advised that patients under continuous treatment should avoid operating machinery. Not recommended during pregnancy & lactation.

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.

Careful consideration is needed for various interacting drugs and physiologic conditions that can alter Theophylline clearance. Dosage adjustment is required prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up. The dose of Theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of time.

Interaction

Alcohol, CNS depressants, anticholinergic drugs, MAOIs.

Allopurinol, cimetidine, norfloxacin, ciprofloxacin, erythromycin, oral contraceptives and propranolol increase serum theophylline levels. Phenytoin, methotrexate and rifampicin lead to decreased serum theophylline levels

Volume of Distribution

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

• 0.3 to 0.7 L/kg

Elimination Route

Well absorbed in the gastrointestinal tract.

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

Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.

Half Life

21-27 hours

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

8 hours

Clearance

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

• 0.29 mL/kg/min [Premature neonates, postnatal age 3-15 days]
• 0.64 mL/kg/min [Premature neonates, postnatal age 25-57 days]
• 1.7 mL/kg/min [Children 1-4 years]
• 1.6 mL/kg/min [Children 4-12 years]
• 0.9 mL/kg/min [Children 13-15 years]
• 1.4 mL/kg/min [Children 16-17 years]
• 0.65 mL/kg/min [Adults (16-60 years), otherwise healthy non-smoking asthmatics]
• 0.41 mL/kg/min [Elderly (>60 years), non-smokers with normal cardiac, 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 cirrhosis]
• 0.35 mL/kg/min [acute hepatitis]
• 0.65 mL/kg/min [cholestasis]
• 0.47 mL/kg/min [Sepsis with multi-organ failure]
• 0.38 mL/kg/min [hypothyroid]
• 0.8 mL/kg/min [hyperthyroid]

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.

Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.

Pregnancy & Breastfeeding use

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

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.

Pregnancy: It is not known whether Theophylline can cause foetal harm when administered to pregnant woman.Xanthines should be given to a pregnant woman only if clearly needed.

Nursing mother: Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. Serious adverse effects in the infant are unlikely unless the mother has toxic serum Theophylline concentrations.

Contraindication

There is no definite contraindication to therapy. It should be used with caution in epilepsy, prostatic hypertrophy, glaucoma and hepatic disease. The ability to drive or operate machinery may be impaired.

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

Hypersensitivity to xanthine derivatives. It is also contraindicated in patients with active peptic ulcer disease and in individuals with underlying seizure disorders (unless receiving appropriate anti-convulsing medication).

Theophylline should not be administered concurrently with other xanthine. Use with caution in patients with hypoxemia, hypertension, or those with history of peptic ulcer. Do not attempt to maintain any dose that is not tolerated.

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 may include nausea, vomiting, gastrointestinal irritation, cramps, convulsions, tachycardia & hypotension. The stomach contents should be emptied & supportive measures employed to maintain circulation, respiration & fluid & electrolyte balance. Electrocardiographic monitoring should be carried out & in severe poisoning charcoal haemoperfusion should be used.

Storage Condition

Store in a cool and dry place, protect from light and moisture. Keep out of the reach of children

Innovators Monograph

You find simplified version here Ashreliv