Asthma is a chronic inflammatory disease characterized by episodes of reversible airways obstruction due to bronchial hyper-responsiveness, inflammation may lead to irreversible obstruction in a few patients. It can be divided by severity into intermittent, mild persistent, moderate persistent and severe persistent. The level of therapy is increased at the severity of the asthma increases with stepping - down if control is sustained.
Administration
Medications for asthma can be administered in several different ways, including inhaled, oral and parenteral (subcutaneous, intramuscular or intravenous).
Initially, therapy is usually administered by inhalation to deliver the drugs to the desired site of action. The doses are thus smaller than would be required with oral administration, although in severe asthma that route may also be necessary. Spacing devices can be fitted to some mattered - dose inhalers to act as reservoirs for the drug to make it easier for the patient (especially if a child) to inhale each dose. A large volume spacer device is recommended for the inhalation of high doses of corticosteroids to reduce oropharyngeal deposition any systemic absorption.
Pregnancy
Poorly controlled asthma in pregnant women can have and adverse effect on the fetus, resulting in perinatal mortality, increased prematurity and low birth - weight. For this reason using medications to obtain optimal control of asthma is justified. Administration of drugs by inhalation during pregnancy has the advantage that plasma drug concentrations are not likely to be high enough to have an effect on the fetus. Acute exacerbations should be treated aggressively in order to avoid fetal hypoxia.
The standard drugs employed in the management of asthma are the beta-adrenergic agonist and corticosteroids. Beta - adrenergic drugs (beta agonists) relax the bronchial smooth muscle to produce bronchodilation by stimulating beta2-adrenergic receptors. Short-acting selective beta2 agonists such as Salbutamol or Terbutaline are the initial drugs of choice; if inhaled they can have an almost immediate bronchodilating effect. Long acting Beta2 agonists such as salmeteral can be given less frequently. However, their onset of action tends to be slower and the full effect may not be seen for several doses. Non-selective beta agonists such as isoprenaline now have little role in the management of asthma.
Corticosteroids are used for their anti-inflammatory properties and to reduce bronchial hyper-responsiveness, they must be taken regularly to achieve maximum benefit.
In addition, Xanthines such as aminophylline or theophylline, and antimuscarinic agents such as Ipratropium bromide may be given for their bronchodilating properties. Prophylactic anti-asthmatic agents such as Sodium cromoglycate can be of benefit, these drugs have anti-inflammatory properties and may be used in conjunction with other therapy or as an alternative to corticosteroids in less severe asthma.
Acute exacerbation of asthma
Severe asthma can be fatal and must be treated promptly and energetically. Acute severe asthma attacks require hospital admission where resuscitation facilities are immediately available. Severe asthma is characterized by persistent dyspnoea poorly relieved by bronchodilators, exhaustion a high pulse rate (usually more than 110/minute) and a very low poor expiratory flow.
As asthma become more sever, wheezing may be absent. Patients should be given oxygen 40 - 60 % (if available) and corticosteroids; for Adults, prednisolone 30 - 60 mg by mouth or hydrocortisone 200 mg (preferably as sodium succinate) intravenously; for children prednisolone 1 - 2 mg/Kg by mouth (1 - 4 years, maximum 20 mg, 5 - 15 years, maximum 40 mg) or hydrocortisone100 mg (preferably as sodium succinate) intravenously; if the patient experiences vomiting the parenteral route may be preferred for the first dose.
Patients should also be given Salbutamol or terbutalline via a nebulizer. In emergency situations where delivery via a nebulizer is not available Salbutamol 100 micrograms by aerosol inhalation can be repeated 10 - 20 times preferably using a large volume spacing device.
If there is little response, the following additional treatment should be considered; ipratropium by nebulizer, aminophylline by slow intravenous injection if the patient has not been receiving theophylline, or administer the beta2-selective adrenoceptor agonist by the intravenous route. The use of epinephrine (adrenaline) in asthma has generally been superseded by beta2-selective adrenoceptor agonists.
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (Chronic bronchitis and emphysema) may be helped by an inhaled short-acting beta2-adrenoroptor agonist used as required or when the accurate obstruction is more sever, by an inhaled anticholinergic (antimuscarinic) bronchodilator or both if necessary. Although many patients are treated with an inhaled corticosteroid its role in chronic obstructive pulmonary disease is not clear at present. A limited trial of high dose inhaled corticosteroid or an oral corticosteroid is recommended for patients with moderate airflow obstruction to determine the extent of the airway reversibility and to ensure that than has not been overlooked.
Adrenaline (Epinephrine)
Injection, 0.1 % in 1 ml ampoule
Indications: - For acute bronchial asthma, and acute anaphylactic reactions; see section 2.5 Cautions, Drug interactions, Contraindications, Side effects; see under section 2.5
Dose and Administration: Subcutaneously or intramuscularly.
Acute bronchial asthma -
Adults: S.C. initially, 0.2 -0.5mg (0.2-0.5ml), repeated every 20 minutes - 4 hours as necessary; Children: S.C. 0.01mg (0.01ml)/ kg of body weight, up to a maximum of 0.5mg(0.5ml)/dose.
Note: If there is no response after 2 adrenaline injections, or if the attack worsens after the first injection, aminophylline should be given intravenously.
Acute anaphylactic reactions -
Adults: S.C, or I.M., initially 0.2 - 0.5mg (0.2ml-0.5ml) repeated as necessary. Maximum - 1mg (1ml) /dose if necessary. Children: S, C., 0.01mg (0.01ml)/Kg of body weight repeated every 15 minutes for 2 doses, then every 4 hours as necessary. Maximum - 0.5mg (0.5ml)/ dose.
Storage: - at room temperature, in a light - resistant container.
Theophylline
Tablet (anhydrous theophylline), 100mg, 200mg, 200mg (s/r)
Elixir, 33mg in each 15 ml (anhydrous theophylline)
Indications: - reversible airways obstruction, acute severe asthma.
Cautions: - peptic ulcer, hyperthyroidism, hypertension, cardiac arrhythmias or other cardiovascular disease, or epilepsy (as these conditions may be exacerbated); heart failure, hepatic dysfunction or chronic alcoholism, acute febrile illness, and to neonates and the elderly (since in all of these circumstances theophylline clearance may be decreased); see also Interactions.
Drug interactions: - concomitant use with other xanthine medications; cimetidine, disulfiram, fluvoxamine, macrolide antibiotics and quinolones, oral contraceptives, thiabendazole, and viloxazine (necessitating dosage reduction); phenytoin and some other anticonvulsants, rifampicin, sulphinpyrazone, and cigarette smoking (necessitating an increase in dose or dosing frequency). Xanthines can potentiate hypokalaemia associated with the administration of beta2-agonists, corticosteroids, and diuretics and hypokalaemia due to hypoxia.
Contraindications: - Hypersensitivity to theophylline or xanthine derivatives; peptic ulcer, coronary artery disease (when, in the physician's judgment, myocardial stimulation might prove harmful).
Dose and Administration -
Theophylline Elixir, Tablet
Usual adult dose
Loading dose -
For patients not currently receiving theophylline preparation:
Oral, the equivalent of 5 mg of anhydrous theophylline per kg of lean (ideal) body weight as a single dose to provide an average peak serum concentration of 10 mcg per ml, ranges 5 to 15 mcg per ml.
For patients currently receiving theophylline preparations:
The loading dose for theophylline is based on the principle that each 0.5 mg of theophylline per kg of lean (ideal) body weight will result in a 1 mcg per ml increase in serum theophylline concentration.
Maintenance -
Oral, the equivalent of anhydrous theophylline, initially, 300 mg per day. After three days, the dosage may be increased, if tolerated to 400 mg per day. After three more days, the dosage may be increased, if tolerated, to 600 mg per day with out measurement of serum concentration.
The total daily adult dose is administered in three or four divided doses given about six to eight hours apart.
Usual pediatric dose:
Loading dose: - see usual adult dose
Maintenance -
Children 1 year of age and older (weighing less than 45 Kg) oral, the equivalent of anhydrous theophylline, 12 to 14 mg per Kg of body weight, up to a maximum of 300 mg, per day in divided doses. The dosage may be increased. If tolerated, after three days to 16 mg per kg of body weight, up to a maximum of 400 mg per day. After three more days, if tolerated, the dosage may be increased to 20 mg per kg of body weight up to a maximum of 600 mg, per day. The total daily dose is administered in four to six divided doses given every four to six hours.
Children weighing more than 45 kg - see usual adult dose.
Theophylline elixir is not recommended in children due to the high alcohol content.
Theophylline sustained release tablet
Usual adult dose: see theophylline tablet; under maintenance dose (adult dose)
Usual pediatric dose: see theophylline tablet; under maintenance dose (pediatric dose).
One-half of the daily theophylline dose may be given at twelve - hour intervals.
Note - Due to the significant variability in extended release product characteristics, pharmacists should not substitute one brand for another with out consulting the prescribing physician unless the product has proven bioequivalence. So that theophylline serum concentrations can be appropriately monitored.
Storage: - store in a well-closed container at room temperature.
Aminophylline (Theophylline and Ethylenediamine)
Tablet, 100mg, 200mg
Tablet (m/r), 100mg, 225mg, 350mg
Injection, 250mg/10ml, 10ml, in 10 and 20ml
Indications: - reversible airways obstruction, acute severe asthma.
Cautions, Drug interactions, Contraindications; see under theophylline
Side effects: - see under theophylline; also allergy to Ethylenediamine can cause urticaria, erythema, and exfoliative dermatitis.
Dose and Administration: -
Tablet, by mouth, 100-300mg, 3-4 times daily, after food.
Tablet (m/r, 225mg), 1 tablet twice daily initially, increased after 1 week to 2 tablets twice daily. Tablet (m/r, 350mg) is for smokers and other patients with decreased theophylline half-life. Tablet (m/r, 100mg), child over 3 years, 6mg/kg twice daily initially, increased after 1 week to 12mg/kg twice daily; some children with chronic asthma may require 13-20mg/kg every 12 hours.
By slow intravenous injection or preferably by slow intravenous infusion. Avoid rapid intravenous injection.
It should be given cautiously, particularly in patients who have previously been taking theophylline and/or ephedrine.
Adults: Slow, I.V., 250-500mg (5mg/kg) over 20 minutes, or diluted with 10ml of water for injection.
Maintenance - If required, 0.5mg/kg of body weight per hour by slow I.V. infusion for a period of 24 hours only.
Children: Slow I.V. 5mg/kg of body weight
Maintenance - If required, 6 months-9 years - 1mg/kg of body weight per hour by slow intravenous infusion.
10 -16 years - 0.8mg/kg of body weight per hour by slow intravenous infusion.
Note: aminophylline is a stable mixture or combination of theophylline and Ethylenediamine; the Ethylenediamine confers greater solubility in water.
Storage: At room temperature protect from light.
Note: The injection should not be used if crystallization has occurred.
Theophylline and Guaifenesin
Tablet 150mg + 90mg
Capsule, 150mg + 90mg; 300mg + 180mg
Elixir, 150mg + 90mg/15ml
Indications: - for relief and/or prevention of symptoms of bronchial asthma and reversible bronchospasm associated with chronic bronchitis and pulmonary emphysema.
Cautions, Drug interactions: - see notes under theophylline
Side effects: - gastroesophageal reflux: see notes under Theophylline
Dose and Administration: - see notes under Theophylline
Storage: - Guaifenesin preparations should be stored in tight containers at room temperature.
Ephedrine + Theophylline
Tablet, 11mg + 120mg
Elixir, 6mg + 30mg in each 5ml
Syrup, 2.24% + 0.30%
Beclomethasone Dipropionate
Oral inhalation (aerosol),50 mcg/dose, 100 mcg/dose
Indications: - prophylaxis of asthma especially if not fully controlled by bronchodilators or cromoglycate.
Cautions: - active or quiescent pulmonary tuberculosis; pregnancy; transferring from systemic steroids.
Side effects: - oral candidiasis (creamy white, curd like patches inside mouth); cough without symptoms of infection; rarely skin rash and difficulty in swallowing; hoarseness.
Contraindications: - bronchiectasis (moderate to severe), sensitivity to the drug or any ingredient (e.g. fluorocarbons, oleic acid) in the formulation.
Dose and Administration: -
Adults: 200 micrograms twice daily or 100 micrograms three or four times daily. Severe cases 600 - 800 micrograms daily; Children: 50 - 100 micrograms two to four times daily.
Note: Gargling and rinsing the mouth with water after each dose is recommended to help prevent hoarseness, throat irritation, and oral candidiasis. The use of a spacing device may also greatly decrease the incidence of these local adverse effects.
Storage: - at room temperature (15- 30oC).
Salbutamol (Albuterol)
Tablet, 2mg, 4mg, 4mg (s/r)
Syrup, 2mg/5ml
Oral inhalation (aerosol), 0.1mg per dose
Indications:- symptomatic treatment of bronchial asthma. It is also indicated for the treatment of reversible bronchospasm associated with bronchitis, pulmonary emphysema, bronchiectasis, and other pulmonary disease.
Cautions: - during pregnancy, breastfeeding
Drug interactions: - anaesthetics such as enflurane, isoflurane, methoxyflurane, maprotiline; Beta adrenergic blocking agents, antihypertensives, CNS stimulants, cocaine, digitalis glycoside, levodopa, monoamine oxidase inhibitor, nitrates, ritodrine, sympathomimetics, thyroid hormones, xanthenes such as aminophylline, caffeine, dyphylline, otriphylline, theophylline.
Contraindications: - cardiac arrhythmias, coronary insufficiency, hypertension, ischemic heart diseases, diabetes mellitus, and hyperthyroidism.
Side effects: - fast heartbeat, nausea, nervousness or restlessness, ponding heartbeat, trembling, chest discomfort or pain, hallucinations.
Dose and Administration -
Tablets - Adults, Oral, 2 to 6mg (base) - three or four times a day initially, the dosage being increased and tolerated up to a maximum of 8mg four times a day.
Children (6-12 years) - oral, 2mg (base) - three or four times a day initially, the dosage being increased and tolerated up to a maximum of 24mg per day in divided doses.
Syrup - Adult, Oral, 2 to 6mg (base) three or four times a day initially, the dosage being increased as needed and tolerated up to a maximum of 8mg four times a day.
Children (2-6 years) - Oral, 0.1mg(base) per kg of body weight three times a day initially, the dosage being increased as needed and tolerated up to 0.2mg per kg of body weight, not to exceed 4mg three times a day.
Children (6-14 years) - Oral, 2mg (base) three or four times a day initially, the dosage being increased as needed and tolerated up to a maximum of 24mg per day in divided doses.
Inhalation (aerosol) - Adult, oral inhalation, 0.18 to 0.2mg (2 inhalations) every four to six hours.
Note: - Shake well before use.
Storage: - Aerosol - store at room temperature away from heat and direct sunlight. Syrup, Tablet - store between 2 and 300c, in a well-closed container, protect from light and from freezing.
Isoprenaline Sulphate
Tablet (Sublingual), 5mg, 10mg
Indications:- symptomatic treatment of bronchial asthma and reversible bronchospasm which may occur association with chronic bronchitis, pulmonary emphysema, bronchiectasis and other chronic obstructive pulmonary diseases.
Cautions: - elderly patients, nursing mothers, diabetic patients with renal or cardiovascular disease (including hypertension, coronary artery disease, coronary insufficiency, angina pectoris degenerative heart disease, hyperthyroidism). Frequent use of sublingual tablet may damage the patient’s teeth because of the acidity of the drug.
Drug interactions: - anaesthetic (general), sympathomimetic such as epinephrine; cocaine, digitalis glycoside, theophylline derivatives, levodopa, nitrates, ritodrine, thyroid hormones.
Contraindications: - pre-existing cardiac arrhythmias, tachycardia.
Side effects: - dryness or irritation of mouth or throat, nervousness, or restlessness, pinkish to red coloration of saliva, insomnia, anxiety, tension, fear, or excitement, chest discomfort or pain, dizziness or light headedness, continuing fast heartbeat, continuing or severe headache.
Dose and Administration: - Subligual, Adult - 10-20mg, not to exceed 60mg; Children - 5-10mg, not to exceed 30mg
Storage: - at room temperature in a well closed, light resistant container.
Ipratropium Bromide
Aerosol Solution, 20mcg/metered
Inhalation; 400mcg/metered inhalation
Indications: - chronic asthma; chronic obstructive pulmonary disease.
Cautions: - prostatic hypertrophy; pregnancy; glaucoma (standard doses unlikely to be harmful; reported with nebulized drug, particularly in association with nebulized salbutamol)
Side effects: dry mouth occasionally reported, rarely urinary retention, constipation.
Dose and Administration:
Chronic asthma or chronic obstructive pulmonary disease, by aerosol inhalation, Adult 20-40micrograms, in early treatment up to 80 micrograms at a time, 3-4 times daily; child up to 6 years, 20 micrograms 3 times daily; 6-12 years, 20-40 micrograms 3 times daily.
Storage: - at room temperature protect from freezing. Protect from light.
Sodium Cromoglycate
Capsules with inhaler - 20 mg
Indications: - indicated as a prophylaxis in the management of bronchial asthma in patients who require continuing symptomatic relief.
*** It has no role in the treatment of an acute attack of asthma, especially status asthmaticus, because it has no intrinsic bronchodilating activity.
It is also indicated to prevent bronchospasm induced by exercise, or by exposure to allergens, cold dry air, environmental pollutants, or other known precipitating factors when exposure is either episodic or continuous
Cautions: - nursing women, pediatric and geriatric patients. Caution should also be used when decreasing the dosage of cromolyn or discontinuing the drug in patients with asthma.
Side effects: - cough, hoarseness, irritation of the throat and trachea, bronchospasm
Contraindications: - sensitivity to cromolyn, coronary artery disease or history of cardiac arrhythmias.
Dose and Administration: -
Asthma, bronchial (prophylaxis): - oral inhalation, 20 mg (1 capsule) four times a day at regular intervals, the dosage being adjusted as needed and tolerated.
Bronchospasm (prophylaxis) - oral inhalation 20 mg (1capsule) as a single dose just prior to exposure to the precipitating factor; or, if used chronically, 20 mg (1 capsule) four times a day at regular intervals, the dosage being adjusted as needed and tolerated.
Children up to 2 years of age - Dosage has not been established
Storage: - capsules containing sodium cromoglycate powder for oral inhalation should be stored at room temperature in tight, light-resistant containers; exposure to excessive moisture and to temperatures greater than 40o should be avoided.
