1. Recommend their use (ELE code: IIIG4a) [Difficulty: ELE: R, Ap, An]

A variety of names have been used to describe this group of medications, including: beta-agonists, beta-adrenergic agonists, catecholamines, sympathomimetic amines, sympathomimetic bronchodilators, and β(beta)-adrenergic bronchodilators. They have the effect of stimulating the body’s sympathetic nerves, which results in bronchodilation and other effects. Be prepared to recommend the use of these types of medications in patients with asthma and chronic obstructive pulmonary disease (COPD [e.g., emphysema, chronic bronchitis]).

A brief review of the autonomic nervous system helps in understanding how these medications (and the following group of medications) work and some side effects that may occur. The autonomic nervous system is not under voluntary control. It is an automatic system designed to regulate metabolism and the vital signs. This system is made up of two branches: the sympathetic nervous system and the parasympathetic nervous system. The lungs, heart, and most other organs are innervated by both branches. The blood vessels in the mucous membranes are innervated only by the sympathetic branch. The parasympathetic nervous system is usually dominant and keeps the body functioning normally. The sympathetic nervous system is an “emergency” system that is dominant during great stress (sometimes called the “fight or flight” system). Adrenaline (or epinephrine) is released by the adrenal glands in these emergencies. Adrenaline causes a number of effects, including one that many respiratory patients need—bronchodilation. The sympathetic nervous system has the following three types of receptors that are located in different organs and are affected by adrenaline and related medications:

2. Administer the prescribed medication (Code: IIIC3, IIID5a, IIID5b) [Difficulty: ELE: R, Ap; WRE: An]

Aerosolized sympathomimetic bronchodilators are usually recommended and given under one of the three following situations:

1. Recommend their use (ELE code: IIIG4a) [Difficulty: ELE: R, Ap, An]

This group of medications works to promote bronchodilation by suppressing the action of the parasympathetic nervous system. This results in the sympathetic nervous system dominating and causing bronchial smooth muscle relaxation. The parasympatholytic (anticholinergic) group has been found to be more effective in helping patients with chronic obstructive pulmonary disease (COPD) than in helping patients with asthma. Be prepared to recommend their use in these types of patients.

2. Administer the prescribed medication (Code: IIIC3, IIID5a, IIID5b) [Difficulty: ELE: R, Ap; WRE: An]

Many patients with COPD and asthma will be treated with nebulized medications from both the sympathomimetic and the parasympatholytic groups. Combivent and DuoNeb combine a sympathomimetic and a parasympatholytic medication. The newest drug in this group, tiotropium bromide (Spiriva), provides the patient with 24 hours of the medication’s benefits. See Table 9-2 for information on the parasympatholytic medications.

1. Recommend use of corticosteroids (ELE code: IIIG4b) [Difficulty: ELE: R, Ap, An]

Corticosteroids affect the respiratory system in two ways: they potentiate the effects of the sympathomimetic agents, and they stop the inflammatory response seen in the airways of asthmatic patients after exposure to an allergen. This prevents mucosal edema from developing. The patient with chronic airflow obstruction, such as asthma or asthmatic bronchitis, should be given inhaled corticosteroids. When they are used as directed, relatively little systemic (bodily) absorption occurs. However, it is best to monitor the patient, especially small children taking inhaled corticosteroids for an extended period, for any side effects. Current guidelines for asthma management classify corticosteroids as “controller” medications that are taken to prevent an asthma attack.

The patient who is diagnosed with status asthmaticus should have systemic corticosteroids promptly administered by the intravenous (IV) route. Examples of commonly used systemic corticosteroids include methylprednisolone (Medrol and Solu-Medrol), prednisone (Deltasone), prednisolone (Meticortelone and Delta-Cortef), cortisone (Cortone), and hydrocortisone (Cortef and Solu-Cortef). These drugs can be lifesavers if used properly. However, prolonged use of large oral or IV doses can lead to serious systemic complications including, but not limited to, immunosuppression, adrenal gland insufficiency, hyperglycemia, and osteoporosis. If a patient has been taking systemic corticosteroids for an extended time, he or she should be gradually weaned from them after an inhaled corticosteroid has been started. It is dangerous to suddenly stop an oral or intravenous corticosteroid that has been used for a prolonged time.

2. Administer the prescribed medication (Code: IIIC3, IIID5a, IIID5b) [Difficulty: ELE: R, Ap; WRE: An]

Table 9-3 shows specific strength and dosage information for the inhaled corticosteroids.

TABLE 9-3 Inhaled Corticosteroids Agents^*

Drug	Brand Name	Formulation and Dosage
Beclomethasone dipropionate HFA	QVAR	MDI: 40 mcg/puff and 80 mcg/puff Adults ≥12 yr: 40-80 mcg twice daily,* or 40-160 mcg twice daily† Children ≥5 yr: 40-80 mcg twice daily

Budesonide Pulmicort DPI: 200 mcg/actuation Turbuhaler Adults: 200-400 mcg bid,^† 200-400 mcg bid,^† 400-800 mcg bid^‡§ Children ≥6 yr: 200 mcg bid Pulmicort DPI: 90 mcg/actuation, 180 mcg/actuation Flexhaler Adults: 180-360 mcg bid usual dose range, 720 mcg bid maximum Children ≥6 yr: 180 mcg bid usual dose, 360 mcg bid maximum Pulmicort SVN: 0.25 mg/2 mL, 0.5 mg/2 mL, 1 mg/ml Respules Children 1-8 yr: 0.5 mg total dose given once daily, or twice daily in divided doses;^*† 1 mg given as 0.5 mg bid or once daily^§ Budesonide and formoterol fumarate HFA Symbicort MDI: Adults ≥12 yr: 80 mcg budesonide with 4.5 mcg formoterol/actuation, 2 puffs bid; and 160 mcg budisonide with 4.5 mcg formoterol/actuation, 2 puffs bid Maximum daily dose: 640 mcg budisonide and 18 mcg formoterol Flunisolide hemihydrate HFA Aerospan MDI: 80 mcg/puff Adults ≥12 yr: 2 puffs bid, adults no more than 4 puffs daily Children 6-11 yr: 1 puff daily, no more than 2 puffs daily Flunisolide AeroBid, AeroBid-M MDI: 250 mcg/puff Adults and children ≥6 yr: 2 puffs bid, adults no more than 4 puffs daily Children ≤15 yr: no more than 2 puffs daily Fluticasone propionate Flovent HFA MDI: 44 mcg/puff, 110 mcg/puff, 220 mcg/puff Adults ≥12 yr: 88 mcg bid,^* 88-220 mcg bid,^† or 880 mcg bid^§ Children 4-11 yr: 88 mcg bid Flovent Diskus DPI: 50 mcg, 100 mcg, 250 mcg Adults: 100 mcg bid^*100-250 mcg bid,^† 1000 mcg bid^§ Children 4-11 yr; 50 mcg twice daily Fluticasone propionate/salmeterol Advair Diskus DPI: 100 mcg fluticasone/50 mcg salmeterol, 250 mcg fluticasone/50 mcg propionate/salmeterol, or 500 mcg fluticasone/50 mcg salmeterol salmeterol Adults and children ≥12 yr: 100 mcg fluticasone/50 mcg salmeterol, 1 inhalation twice daily, about 12 hr apart (starting dose if not currently on inhaled corticosteroids) Maximum recommended dose 500 mcg fluticasone/50 mcg salmeterol twice daily Children ≥4 yr: 100 mcg fluticasone/50 mcg salmeterol, 1 inhalation twice daily, about 12 hr apart (for those who are symptomatic while taking an inhaled corticosteroid) Advair HFA MDI: 45 mcg fluticasone/21 mcg salmeterol, 115 mcg fluticasone/21 mcg salmeterol, or 230 mcg fluticasone/21 mcg salmeterol salmeterol, Adults and children ≥12 yr: 2 inhalations twice daily, about 12 hr apart Mometasone furoate Asmanex DPI: 220 mcg^‡ actuation, 110 mcg actuation for children 4-11 Twisthaler Adults and children ≥12 yr: 220-440 mcg daily,^† 220-440 mcg daily,^* 480-880 mcg daily^§ Triamcinolone acetonide Azmacort MDI: 75 mcg/puff Adults ≥12 yr: 2 puffs tid or qid Children ≥6 yr: 1-2 puffs tid or qid

bid, twice daily; qid, four times daily; tid, three times daily.

* Detailed prescribing information should be obtained from the manufacturer’s package insert.

† Recommended starting dose if on bronchodilators alone.

‡ Recommended starting dose if on inhaled corticosteroids previously.

§ Recommended starting dose if on oral corticosteroids previously.

Modified from Gardenhire DS: Rau’s Respiratory care pharmacology, ed 7, St Louis, 2008, Mosby.

The patient who is using any of these medications must gargle and rinse out his or her mouth after each use. If not, the patient runs the risk of developing a fungal infection of the mouth and throat. Note that there are now two inhaled medications (Advair and Symbicort) that combine a corticosteroid and a long-acting beta agonist (LABA).

Note: While past Written Registry Examinations have included a question concerning nonsteroidal antiinflammatory drugs (NSAIDs), they are not included in the current detailed content outline. They are include here for the sake of completeness. There are several different types of over-the-counter medications. None is as powerful an antiinflammatory as the corticosteroid drugs. Note the other clinical uses of acetylsalicylic acid and ibuprofen:

1. Recommend the use of cromolyn sodium (ELE code: IIIG4b) [Difficulty: ELE: R, Ap, An]

Cromolyn sodium (Intal) and nedrocromil sodium (Tilade) are indicated to prevent an asthma attack. They accomplish this by coating the mast cells found in the airways so that they do not degranulate and rupture. Without pretreatment, the mast cells of asthmatic patients would rupture when exposed to immunoglobulin E (IgE) from their allergen(s). This mast cell rupture would result in the spilling of leukotriene agents, histamine, and other chemical mediators that cause the bronchospasm, airway edema, and increased airway secretions of an asthma attack.

2. Administer the prescribed medication (Code: IIIC3, IIID5a, IIID5b) [Difficulty: ELE: R, Ap; WRE: An]

When cromolyn sodium, or nedrocromil sodium, is inhaled at least 1 week before exposure to the allergen, the asthmatic reaction is prevented or reduced. Cromolyn was first made available through a dry powder inhaler and is now only available by metered dose inhaler or small volume nebulizer (SVN). Nedrocromil sodium is similar to cromolyn in its use and effects. It is available in a metered dose inhaler. See Table 9-4 for detailed information on both medications.

TABLE 9-4 Inhaled Nonsteroidal Antiasthma Agents^*

Drug	Brand Name	Formulation and Dosage
CROMOLYN-LIKE (MAST CELL STABILIZERS)
Cromolyn sodium†	Intal	MDI: 800 mcg/actuation
		Adults and children ≥5 yr: 2 inhalations 4 times daily
		SVN: 20 mg/amp or 20 mg/vial
		Adults and children ≥2 yr: 20 mg inhaled 4 times daily
	Nasalcrom	Spray: 40 mg/mL (4%), gives 5.2 mg of drug
		Adults and children ≥2 yr: 1 spray each nostril, 3-6 times daily every 4-6 hr
Nedocromil sodium	Tilade	MDI: 1.75 mg/actuation
		Adults and children ≥6 yr: 2 inhalations 4 times daily
ANTILEUKOTRIENES
Montelukast	Singulair	Tablets: 10 mg, 4 mg, and 5 mg cherry-flavored chewable; 4 mg packet of granules
		Adults and children ≥15 yr: one 10 mg tablet daily in evening
		Children 6-14 yr: one 5 mg chewable tablet daily
		Children 2-5 years: one 4 mg chewable tablet or one 4 mg packet of granules daily
		Children 6-23 months: one 4 mg packet of granules daily
Zafirlukast	Accolate	Tablets: 10 and 20 mg
		Adults and children ≥12 yr: 20 mg (1 tablet) twice daily, without food
		Children 5-11 yr: 10 mg twice daily
Zileuton	Zyflo	Tablets: 600 mg
	Zyflo CR	Adults and children ≥12 yr: one 600 mg tablet 4 times a day
MONOCLONAL ANTIBODY
Omalizumab	Xolair	Adults and children ≥12 yr: subcutaneous injection every 4 weeks; dose dependent on patient’s weight and serum IgE level

* Detailed prescribing information should be obtained from the manufacturer’s package insert.

† Note: Cromolyn sodium is also available in an oral concentrate giving 100 mg in 5 mL (Gastrocrom) for treatment of systemic mastocytosis, and as an ophthalmic 4% solution (Opticrom, 40 mg/mL) for treatment of vernal keratoconjunctivitis.

Modified from Gardenhire DS: Rail’s Respiratory care pharmacology, ed 7, St Louis 2008, Mosby.

It is very important to understand that both drugs are taken for prophylactic purposes to prevent an asthma attack. They are contraindicated during an asthma attack. A patient experiencing acute bronchospasm should be treated with a fast sympathomimetic bronchodilator, as previously discussed.

1. Recommend the use of acetylcysteine (ELE code: IIIG4c) [Difficulty: ELE: R, Ap, An]

N-Acetylcysteine/acetylcysteine/NAC (Mucomyst, Mucosil) is a mucolytic drug that has been widely used for many years with patients who have thick (viscous) mucus or mucus plugs. However, its use for the mycolytic effect is now controversial and some authors have advocated for the discontinuation of its clinical use. In the past, the NBRC has included questions where acetylcysteine (Mucomyst) would be indicated as a mucolytic.

Know that there are two clinical concerns with this medication. Acetylcysteine has a bad odor (rotten eggs) that may lead to nausea and vomiting in some patients. Of greater concern is the stimulation of bronchospasm in some asthmatic patients. Therefore it is wise to pretreat these patients with an aerosolized sympathomimetic bronchodilator before acetylcysteine is nebulized. Any fast-onset bronchodilator can be used in the usual dose. Because of the lack of proven clinical effectiveness and the noted hazards, acetylcysteine is no longer recommended in patients with cystic fibrosis. It is still used with chronic bronchitis patients as long as the noted precautions are taken.

2. Administer the prescribed medication (Code: IIIC3, IIID5a) [Difficulty: ELE: R, Ap; WRE: An]

Mucomyst is usually administered with a small volume nebulizer (SVN) or with intermittent positive-pressure breathing (IPPB). Most adult patients are given up to 3 to 5 mL of the 20% solution or up to 6 to 10 mL of the 10% solution. The 20% solution is often diluted with an equal volume of normal saline solution. Direct instillation of 1 to 2 mL of the drug into the trachea also helps to liquefy secretions. The manufacturer recommends that all medication in a vial be used within 96 hours or discarded. It should be stored in the refrigerator. A slightly purple color is commonly seen after the vial has been opened, but it can still be used safely. See Table 9-5 for specific information.

1. Recommend the use of RhDNAse (ELE code: IIIG4c) [Difficulty: ELE: R, Ap, An]

Dornase alfa (Pulmozyme; the NBRC refers to this drug as recombinant human deoxyribonuclease [RhDNAse]) is a proteolytic drug that has been approved for use in the treatment of patients with cystic fibrosis. It works by breaking up strands of DNA found in the secretions of these patients with a pulmonary infection.

2. Administer the prescribed medication (Code: IIIC3, IIID5a) [Difficulty: ELE: R, Ap; WRE: An]

Usually a single daily dose of 2.5 mL of solution (containing 2.5 mg of dornase alfa) is inhaled by SVN. Store the drug in a refrigerator, and protect it from strong light. It has no serious side effects. See Table 9-5 for detailed information.

1. Recommend the use of hypertonic saline (ELE code: IIIG4c) [Difficulty: ELE: R, Ap, An]

The various saline solutions (and sterile water) are known collectively as “bland” aerosols, because they have no direct pharmacologic effect on the lungs and airways. When they are inhaled as aerosols, however, a vagal nerve–mediated reflex causes the bronchial/submucosal glands to release more watery secretions. Therefore a saline aerosol is commonly used to help liquefy secretions and induce a patient to expel sputum. Recent clinical experience has shown hypertonic saline to be an effective mucolytic in cystic fibrosis patients.

2. Administer the prescribed medication (Code: IIIC3, IIID5a) [Difficulty: ELE: R, Ap; WRE: An]

The various saline solutions are given through an SVN or IPPB treatment or, more commonly, mixed with a bronchodilator medication. See Table 9-5 and Box 9-2 for information on the various saline solutions.