Nebulized bronchodilators

In cases of severe acute asthmatic attacks, bronchodilators and steroids for direct dehveiy to the lungs may be needed in large doses. This is achieved by direct inhalation via a nebulizer device this converts a liquid into a mist or fine spray. The dmg is diluted in small volumes of Water for Injections BP before loading into the reservoir of the machine. This vehicle must be sterile and preservative-fiee and is therefore prepared as a terminally sterilized unit dose in polyethylene nebules. 

Nebulized short-acting bronchodilator therapy (e.g., albuterol and ipratropium)... 

Albuterol is the preferred bronchodilator for treatment of acute exacerbations because of its rapid onset of action. Ipratropium can be added to allow for lower doses of albuterol, thus reducing dose-dependent adverse effects such as tachycardia and tremor. Delivery can be through metered-dose inhaler (MDI) and spacer or nebulizer. The nebulizer route is preferred in patients with severe dyspnea and/or cough that would limit delivery of medication through an MDI with spacer. If response is inadequate, theophylline can be considered however, clinical evidence supporting its use is lacking. 

Conway, S. and Watson, A. 1997. Nebulized bronchodilators, corticosteroids and rhDNase in adult patients with cystic fibrosis. Thorax 52(2), S64-S68. 

Ipratropium bromide has a slower onset of action than short-acting /J2-agonists (15 to 20 minutes vs. 5 minutes for albuterol). For this reason, it may be less suitable for as-needed use, but it is often prescribed in this manner. Ipratropium has a more prolonged bronchodilator effect than short-acting /l2-agonists. Its peak effect occurs in 1.5 to 2 hours and its duration is 4 to 6 hours. The recommended dose via MDI is two puffs four times a day with upward titration often to 24 puffs/day. It is also available as a solution for nebulization. The most frequent patient complaints are dry mouth, nausea, and, occasionally, metallic taste. Because it is poorly absorbed systemically, anticholinergic side effects are uncommon (e.g., blurred vision, urinary retention, nausea, and tachycardia). 

Bronchodilators may be administered via MDIs or nebulization with equal efficacy. Nebulization may be considered for patients with severe dyspnea who are unable to hold their breath after actuation of an MDI. 

Zainudin, B.M.Z., Biddiscombe. M., Tolfree, S.E.J., Short, M., and Spiro, S.G., Comparison of bronchodilator responses and deposition patterns of salbutamol inhaled from a pressurized metered dose inhaler, as a dry powder, and as a nebulized solution, Thorax, 45 469-473 (1990). 

Adjunctive treatment of viscid mucus secretions from chronic hronchopulmonary disease and for pulmonary complications of cystic fibrosis Nebulization Alert Bronchodilators should be given 15 min before acetylcysteine. 3-5 ml (20% solution) 3-4 times a day or 6-10 ml (10% solution) 3-4 times a day. Range 1-10 ml (20% solution) q2-6h or 2-20 ml (10% solution) q2-6h. ... 

Albuterol, terbutaline, metaproterenol, and pirbuterol are available as metered-dose inhalers. Given by inhalation, these agents cause bronchodilation equivalent to that produced by isoproterenol. Bronchodilation is maximal within 15-30 minutes and persists for 3-4 hours. All can be diluted in saline for administration from a hand-held nebulizer. Because the particles generated by a nebulizer are much larger than those from a metered-dose inhaler, much higher doses must be given (2.5-5.0 mg versus 100-400 meg) but are no more effective. Nebulized therapy should thus be reserved for patients unable to coordinate inhalation from a metered-dose inhaler. 

Albuterol Selective B2 agonist Prompt, efficacious bronchodilation Asthma, chronic obstructive pulmonary disease (COPD) drug of choice in acute asthmatic bronchospasm Aerosol inhalation duration several hours also available for nebulizer and parenteral use Toxicity. Tremor, tachycardia t overdose arrhythmias... 

Epinephrine Nonselective and agonist Bronchodilation plus all other sympathomimetic effects on cardiovascular and other organ systems (see Chapter 9) Anaphylaxis, asthma, others (see Chapter 9) rarely used for asthma (B 2-selective agents preferred) Aerosol, nebulizer, or parenteral see Chapter 9... 

Ipratropium Atrovent HFA, Atrovent Nasal) [Bronchodilator/ Anticholinergic] Uses Bronchospasm w/ COPD, rhinitis, rhinorrhea Action Synthetic anticholinergic similar to atropine antagonizes acetylcholine receptors, inhibits mucous gland secretions Dose Adults Peds >12 y. Nebuliza-tion 500 meg in 2.5-3.0 mL NS Peds. Nebulization 125-250 meg in 2.5-3.0 mL NS Caution [B, +/-] w/ inlial insulin Contra Allergy to soya lecitlrin/related foods Disp HFA met-dose inlial 18 meg/dose inlial soln 0.02% nasal spray 0.03,... 

Q10 Other bronchodilator agents include nebulized ipratropium. Ipratropium is a muscarinic receptor antagonist that helps to relax bronchial smooth muscle which has contracted via parasympathetic stimulation. The xanthines theophylline and aminophylline (theophylline ethylenediamine) are alternative bronchodilator agents. These agents may act as phosphodiesterase inhibitors and, although they have been used as bronchodilators for many years, adverse CNS, GI and cardiovascular effects may limit their usefulness. 

Q8 The dry-powder type of inhaler used to deliver bronchodilators and corticosteroids to the lung by inhalation can sometimes irritate the airways and cause further bronchoconstriction. It is useful to nebulize the drug, that is deliver it to the lung in solution as an aerosol. So the chief advantage of the nebulizer is that it allows drugs to be delivered deep into Carmen s lung, without causing irritation and bronchoconstriction. 

The dose and frequency of bronchodilators are increased during acute exacerbations to provide symptomatic rehef. Short-acting j32-agonists are preferred because of their rapid onset of action. Anticholinergic agents may be added if symptoms persist despite increased doses of )52-agonists. Bronchodilators may be administered via MDIs or nebulization with equal efficacy. Nebulization may be considered for patients with severe dyspnea who are unable to hold their breath after actuation of an MDI. 

IPRATROPIUM BRONCHODILATORS -SALBUTAMOL A few reports of acute angle closure glaucoma when nebulized ipratropium and salbutamol were coadministered Ipratropium dilates the pupil, which i drainage of aqueous humour, while salbutamol t production of aqueous humour Warn patients to prevent the solution to mist or enter the eye. Extreme caution in co-administering these bronchodilators by the nebulized route in patients with a history of acute closed-angle glaucoma... 

Corticosteroid use is controversial. Animal models have shown positive results in hastening recovery from severe chlorine gas poisoning however, administration to humans has not been shown to provide any significant change (Traub et al, 2002). Wang et al (2004) demonstrated that pigs exposed to chlorine gas responded better to a combination of aerosolized bronchodilators and corticosteroids (terbu-taline, budesonide) than to either therapy alone. Sheep nebulized with 4% sodium bicarbonate had decreased mortality and improved oxygenation after inhalation of chlorine gas (Chisholm et al, 1989). 

Blacker, R. Morton, R.W. Mitchell, J.P. Nagel, M.W. Hess, D.R. The Effect of Small Volume Nebulizer (SVN) Design on Fine Particle Mass Delivery of a Bronchodilator, Present at Drug Delivery to the Lungs, London, UK, Dec., 1999. 

Salbutamol Comparison of lung deposition and bronchodilator response between MDI, DPI, and nebulizer [12]... 

Nebulizers are generally used to treat acute exacerbations of asthma or chronic obstructive pulmonary disease. Other indications include long-term bronchodilator treatment of chronic airflow obstruction prophylactic treatment for asthma antimicrobial drugs for cystic fibrosis, bronchiectasis, and HIV/AIDS and symptomatic relief in palliative care. 

When drugs other than bronchodilators are being nebulized, equipment known to provide a suitable output should be used, and specific instructions should be given to patients. Such treatment should be supervised by hospital specialists. 

Nebulization times for bronchodilators should be less than 10 min. Nebulization times and correct operation of devices should be familiar to the patients. 

In another investigation, a single dose of 1.25 mg nebulized R-salbutamol, administered to asthmatics, produced equivalent bronchoprotection, bronchodilatation, tachycardia, and restlessness to that given by 2.5 mg of racemic salbutamol (26). In a further study, asthmatic patients were treated for 28 days with racemic or R-salbutamol administered by nebulizer three times a day. Improvement in FEVi was similar after R-salbutamol 0.63 mg and racemic salbutamol 2.5 mg and greatest with R-salbutamol 1.25 mg. Racemic salbutamol 1.25 mg had the least bronchodilator effect, especially after chronic dosing (27). 

Benzalkonium chloride at concentrations greater than 0.005 mg/ml causes histamine release from mast cells in vitro. At a concentration of 0.03 mg/ml an excess of 90% of the histamine content is released (5). This is in the range of the minimum concentration of benzalkonium chloride recommended as a disinfectant (0.025 mg/ml). Inhalation of benzalkonium chloride nebulizer solution causes concentration-related falls in FEVi in patients with asthma (6). Benzalkonium chloride 0.3 mg also causes a temporary increase in airway reactivity to histamine. This amount of benzalkonium chloride is similar to that in a 2.5 mg dose from a multidose vial of salbutamol (7). Ipratropium containing benzalkonium chloride 0.25 mg/ml causes bronchoconstriction in a proportion of patients with asthma. BronchodUatation is seen when 2 ml (0.5 mg) of preservative-free ipratropium bromide solution is inhaled (8). Benzalkonium chloride 0.1 mg/ml does not alter the bronchodUator effect of salbutamol. The difference between salbutamol and ipratropium may be the lower concentration of benzalkonium chloride in the salbutamol solution (0.1 versus 0.25 mg/ml) and the greater potency and more rapid onset of the bronchodilator response to salbutamol (9). Individual case reports suggest that... 

Mulpeter KM, Walsh JB, O Connor M, O Connell F, Burke C. Ocular hazards of nebulized bronchodilators. Postgrad Med J 1992 68(796) 132-3. 

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