Respiratory Drugs



Respiratory Drugs


Objectives


When you reach the end of this chapter, you will be able to do the following:



Drug Profiles



Key Terms


Allergen Any substance that evokes an allergic response. (p. 589)


Allergic asthma Bronchial asthma caused by hypersensitivity to an allergen or allergens. (p. 589)


Alveoli Microscopic sacs in the lungs where oxygen is exchanged for carbon dioxide; also called air sacs. (p. 589)


Antibodies Immunoglobulins produced by lymphocytes in response to bacteria, viruses, or other antigenic substances. (p. 590)


Antigen A substance (usually a protein) that causes the formation of an antibody and reacts specifically with that antibody. (p. 590)


Asthma attack The onset of wheezing together with difficulty breathing. (p. 589)


Bronchial asthma The general term for recurrent and reversible shortness of breath resulting from narrowing of the bronchi and bronchioles; it is often referred to simply as asthma. Key characteristics are inflammation, bronchial smooth muscle spasticity, and sputum production; inflammation is the most important. (p. 589)


Bronchodilators Medications that improve airflow by relaxing bronchial smooth muscle cells (e.g., xanthines, adrenergic agonists). (p. 591)


Chronic bronchitis Chronic inflammation and low-grade infection of the bronchi. (p. 589)


Emphysema A condition of the lungs characterized by enlargement of the air spaces distal to the bronchioles. (p. 589)


Immunoglobulins Proteins belonging to any of five structurally and antigenically distinct classes of antibodies present in the serum and external secretions of the body; they play a major role in immune responses; immunoglobulin is often abbreviated Ig. (p. 590)


Lower respiratory tract (LRT) The division of the respiratory system composed of organs located almost entirely within the chest. (p. 589)


Status asthmaticus A prolonged asthma attack. (p. 589)


Upper respiratory tract (URT) The division of the respiratory system composed of organs located outside the chest cavity (thorax). (p. 589)


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Anatomy, Physiology, and Pathophysiology Overview


The main function of the respiratory system is to deliver oxygen to, and remove carbon dioxide from, the cells of the body. To perform this deceptively simple task requires a very intricate system of tissues, muscles, and organs called the respiratory system. It consists of two divisions or tracts: the upper and lower respiratory tracts. The upper respiratory tract (URT) is composed of the structures that are located outside of the chest cavity or thorax. These are the nose, nasopharynx, oropharynx, laryngopharynx, and larynx. The lower respiratory tract (LRT) is located almost entirely within the thorax and is composed of the trachea, all segments of the bronchial tree, and the lungs. The URT and LRT have four main accessory structures that aid in their overall function. These are the oral cavity (mouth), the rib cage, the muscles of the rib cage (intercostal muscles), and the diaphragm. The upper and lower respiratory tracts together with the accessory structures make up the respiratory system. Elements of this system are in constant communication with each other as they perform the vital function of respiration and the exchange of oxygen for carbon dioxide.


The air we breathe is a mixture of many gases. During inhalation, oxygen molecules from the air diffuse across the semipermeable membranes of the alveoli, where they are exchanged for carbon dioxide molecules, which are then exhaled. The lungs also filter, warm, and humidify the air. Oxygen is then delivered to the cells by the blood vessels of the circulatory system, where the respiratory system transfers the oxygen it has extracted from inhaled air to the hemoglobin protein molecules contained within red blood cells. Also within the circulatory system, the cellular metabolic waste product carbon dioxide is collected from the tissues by the red blood cells. This waste is then transported back to the lungs via the circulatory system, where it diffuses back across the alveolar membranes and is then exhaled into the air. The respiratory system also plays a central role in speech, smell, and regulation of pH (acid-base balance).


Pathophysiology of Diseases of the Respiratory System


Several diseases impair the function of the respiratory system. Those that affect the URT include colds, rhinitis, and hay fever. These conditions and the drugs used to treat them are discussed in Chapter 36. The major diseases that impair the function of the LRT include asthma, emphysema, and chronic bronchitis. All of these diseases have one feature in common; they all involve the obstruction of airflow through the airways. Chronic obstructive pulmonary disease (COPD) is the name applied collectively to emphysema and chronic bronchitis, because the obstruction is relatively constant. Asthma that is persistent and present most of the time despite treatment is also considered a COPD. Cystic fibrosis and infant respiratory distress syndrome are other disorders that affect the LRT, but they are not a focus of discussion in this chapter because treatment for them places more emphasis on nonpharmacologic than on pharmacologic measures.


Asthma


Bronchial asthma is defined as a recurrent and reversible shortness of breath and occurs when the airways of the lung (bronchi and bronchioles) become narrow as a result of bronchospasm, inflammation and edema of the bronchial mucosa, and the production of viscous (sticky) mucus. The alveolar ducts and alveoli distal to the bronchioles remain open, but the obstruction to the airflow in the airways prevents carbon dioxide from getting out of the air spaces and oxygen from getting in. Symptoms include wheezing and difficulty breathing. When an episode has a sudden and dramatic onset, it is referred to as an asthma attack. Most asthma attacks are short, and normal breathing is subsequently recovered. However, an asthma attack may be prolonged and may not respond to typical drug therapy. This is a condition known as status asthmaticus and requires hospitalization. The onset of asthma occurs before 10 years of age in 50% of patients and before 40 years of age in about 80% of patients.


There are different types of asthma: intrinsic (occurring in patients with no history of allergies), extrinsic (occurring in patients exposed to a known allergen), exercise induced, and drug induced. Allergic asthma, or extrinsic asthma, is caused by a hypersensitivity to an allergen or allergens in the environment. An allergen is any substance that elicits an allergic reaction. In patients with seasonal asthma, the allergen is a substance such as pollen or mold, which is present only periodically (seasonally). The offending allergens in patients with nonseasonal asthma are substances such as dust, mold, and animal dander, which are present in the environment throughout the year. Cigarette smoke, from either smoking or exposure to secondhand smoke, is another common allergen. Examples of common food allergens include nuts, eggs, and corn. Exposure to the offending allergen in a patient with allergic asthma causes an immediate allergic reaction in the form of an asthma attack. This attack is mediated by antibodies already present in the patient’s body that chemically recognize the allergen to be a foreign substance, or antigen. These antibodies are specialized immune system proteins known as immunoglobulins. The antibody in individuals with asthma is usually immunoglobulin E (IgE), which is one of the five types of antibodies in the body (the others are IgG, IgA, IgM, and IgD). On exposure to the allergen, the patient’s body responds by mounting an immediate and potent antigen-antibody reaction (immune response). This reaction occurs on the surfaces of cells such as mast cells that are rich in histamines, leukotrienes, and other substances involved in the immune response. These substances are collectively known as inflammatory mediators, and they are released from the mast cells as part of the immune response. This in turn, as described in Chapter 36, triggers the mucosal swelling and bronchoconstriction that are characteristic of an allergic asthma attack. The sequence of events that occurs in a patient with allergic asthma is shown in Box 37-1.



The specific cause of intrinsic, or idiopathic, asthma is unknown. It is not mediated by IgE, and there is often no family history of allergies in affected patients. However, certain factors have been noted to precipitate asthma attacks in these patients, including respiratory infections, stress, and cold weather. Patients with exercise-induced asthma have bronchospasm at the beginning of exercise, and symptoms stop when exercise is halted. Drug-induced asthma can be the result of different drugs including NSAIDs (see Chapter 44), beta blockers (see Chapters 22 and 24), sulfites, or certain foods. Patients with any type of asthma who know their suspected “triggers,” whether an allergen, the weather, or another factor, are advised to avoid these triggers as much as is feasible as part of managing their disease. When it is not feasible or advisable to avoid a certain trigger (e.g., exercise), patients need to work with their prescribers to prevent the response to these triggers through appropriate drug therapy (e.g., use of a bronchodilator inhaler before exercise or other strenuous activity).


The National Asthma Education and Prevention Panel (NAEPP) of the National Heart, Lung, and Blood Institute has maintained ongoing guidelines for the diagnosis and management of asthma since 1989. The current guideline revision was published in 2007. In general, these guidelines classify asthma medications as either for long-term symptom control or rapid symptom relief. The specific drugs in each classification are listed in Box 37-2. The guidelines advocate the use of a stepwise approach in the treatment of asthma. The particular steps and recommended drug classifications for treatment at each step are listed in Table 37-1.




Chronic Bronchitis


Chronic bronchitis is a continuous inflammation and low-grade infection of the bronchi. The inflammation in the associated bronchioles (smaller bronchi) is responsible for most of the airflow obstruction. Chronic bronchitis involves the excessive secretion of mucus and certain pathologic changes in the bronchial structure. The disease can arise as a result of repeated episodes of acute bronchitis or in the context of chronic generalized diseases. It is usually precipitated by prolonged exposure to bronchial irritants. One of the most common is cigarette smoke. Some patients acquire the disease because of other predisposing factors such as viral or bacterial pulmonary infections during childhood. Others may have mild impairment of the ability to inactivate proteolytic (protein-destroying) enzymes, which then damage the airway mucosal tissues. Unknown genetic characteristics may be responsible as well.


Emphysema


Emphysema is a condition in which the air spaces enlarge as a result of the destruction of the alveolar walls. This appears to be caused by the effect of proteolytic enzymes released from leukocytes in response to alveolar inflammation. Because the alveolar walls are partially destroyed, the surface area available for oxygen and carbon dioxide exchange is reduced, which impairs effective respiration. As with chronic bronchitis, cigarette smoke appears to be the primary irritant responsible for precipitating the underlying inflammation that leads to the development of emphysema. There is also an associated genetic deficiency of the enzyme alpha1-antitrypsin.


Treatment of Diseases of The Lower Respiratory Tract


In the past, the treatment of asthma and other COPDs was focused primarily on the use of drugs that cause the airways to dilate. Now there is a greater understanding of the pathophysiology of these diseases. The emphasis of research has shifted from the bronchoconstriction component of the disease to the inflammatory component. This is also reflected in the various medication classes used to treat COPDs, although bronchodilators still play an important role. A synopsis of the mechanisms of action of the various classes of antiasthmatic drugs is provided in Table 37-2. Figure 37-1 gives an overview of the various drugs used in asthma.




Pharmacology Overview


Bronchodilators


Bronchodilators are an important part of the pharmacotherapy for all respiratory diseases. These drugs relax bronchial smooth muscle, which causes dilation of the bronchi and bronchioles that are narrowed as a result of the disease process. There are three classes of such drugs: beta adrenergic agonists, anticholinergics, and xanthine derivatives.


Beta-Adrenergic Agonists


The beta adrenergic agonists are a group of drugs that are commonly used during the acute phase of an asthmatic attack to quickly reduce airway constriction and restore airflow to normal. They are agonists, or stimulators, of the adrenergic receptors in the sympathetic nervous system. The beta and alpha adrenergic receptors are discussed in Chapters 18 and 19. The beta agonists imitate the effects of norepinephrine on beta receptors. For this reason, they are also called sympathomimetic bronchodilators. The beta agonists are categorized by their onset of action. Short-acting beta agonist (SABA) inhalers include albuterol (Ventolin), levalbuterol (Xopenex), pirbuterol (Maxair), terbutaline (Brethine), and metaproterenol (Alupent). Long-acting beta agonist (LABA) inhalers include arformoterol (Brovana), formoterol (Foradil, Perforomist), and salmeterol (Serevent). Because the LABAs have a longer onset of action, they must never be used for acute treatment. Patients must be taught to use the SABAs as rescue treatment.


Mechanism of Action and Drug Effects


The beta agonists dilate airways by stimulating the beta2-adrenergic receptors located throughout the lungs.


There are three subtypes of these drugs, based on their selectivity for beta2 receptors:




These drugs can also be categorized according to their routes of administration as oral, injectable, or inhaled. The various beta agonist bronchodilators are listed in Table 37-3.



The bronchioles are surrounded by smooth muscle. When the smooth muscle contracts, the airways are narrowed and the amount of oxygen and carbon dioxide exchanged is reduced. The action of beta agonist bronchodilators begins at the specific receptor stimulated and ends with the dilation of the airways. However, many reactions must take place at the cellular level for this bronchodilation to occur. When a beta2-adrenergic receptor is stimulated by a beta agonist, adenylate cyclase is activated and produces cyclic adenosine monophosphate (cAMP). Adenylate cyclase is an enzyme needed to make cAMP. The increased levels of cAMP cause bronchial smooth muscles to




relax, which results in bronchial dilation and increased airflow into and out of the lungs.


Nonselective adrenergic agonist drugs such as epinephrine also stimulate alpha-adrenergic receptors, causing constriction within the blood vessels. This vasoconstriction reduces the amount of edema or swelling in the mucous membranes and limits the quantity of secretions normally produced by these membranes. In addition, these drugs stimulate beta1 receptors, which results in cardiovascular adverse effects such as an increase in heart rate, force of contraction, and blood pressure, as well as central nervous system (CNS) effects such as nervousness and tremor.


Drugs such as albuterol that predominantly stimulate the beta2 receptors have more specific drug effects and cause less adverse effects. By primarily stimulating the beta2-adrenergic receptors of the bronchial and vascular smooth muscles, they cause bronchodilation and may also have a dilating effect on the peripheral vasculature, which results in a decrease in diastolic blood pressure.


Indications


The primary therapeutic effect of the beta agonists is the prevention or relief of bronchospasm related to bronchial asthma, bronchitis, and other pulmonary diseases. However, they are also used for effects outside the respiratory system. Because some of these drugs have the ability to stimulate both beta1– and alpha-adrenergic receptors, they may be used to treat hypotension and shock (see Chapter 18).


Contraindications


Contraindications include known drug allergy, uncontrolled hypertension or cardiac dysrhythmias, and high risk of stroke (because of the vasoconstrictive drug action).


Adverse Effects


Mixed alpha/beta agonists produce the most adverse effects because they are nonselective. These include insomnia, restlessness, anorexia, cardiac stimulation, hyperglycemia, tremor, and vascular headache. The adverse effects of the nonselective beta agonists are limited to beta-adrenergic effects, including cardiac stimulation, tremor, anginal pain, and vascular headache. The beta2 drugs can cause both hypertension and hypotension, vascular headaches, and tremor. Overdose management may include careful administration of a beta blocker while the patient is under close observation due to the risk of bronchospasm. Because the half-life of most adrenergic agonists is relatively short, the patient may just be observed while the body eliminates the medication.


Interactions


When nonselective beta blockers are used with the beta agonist bronchodilators, the bronchodilation from the beta agonist is diminished. The use of beta agonists with monoamine oxidase inhibitors and other sympathomimetics is best avoided because of the enhanced risk for hypertension. Patients with diabetes may require an adjustment in the dosage of their hypoglycemic drugs, especially patients receiving epinephrine, because of the increase in blood glucose levels that can occur.


Dosages


For dosage information on selected beta agonists, see the table on this page.


Drug Profiles


♦ albuterol


Albuterol (Proventil) is a short-acting beta2-specific bronchodilating beta agonist. Other similar drugs include bitolterol (Tornalate), levalbuterol (Xopenex), pirbuterol (Maxair), and terbutaline (Brethine). Albuterol is the most commonly used drug in this class. If albuterol is used too frequently, dose-related adverse effects may be seen, because albuterol loses its beta2-specific actions, especially at larger dosages. As a consequence, the beta1 receptors are stimulated, which causes nausea, increased anxiety, palpitations, tremors, and an increased heart rate.


Albuterol is available for both oral and inhalational use. Inhalational dosage forms include metered-dose inhalers (MDIs) as well as solutions for inhalation. The levorotatory isomeric form of albuterol, levalbuterol, is sometimes prescribed as an albuterol alternative for patients with certain risk factors (e.g., tachycardia, including tachycardia associated with albuterol treatment).



♦ salmeterol


Salmeterol (Serevent) is a long-acting beta2 agonist bronchodilator. Other long-acting inhalers include formoterol (Foradil, Perforomist) and arformoterol (Brovana). The long-acting inhalers are never to be used for acute treatment. Salmeterol is used for the maintenance treatment of asthma and COPD and is used in conjunction with an inhaled corticosteroid. It is given twice daily for maintenance treatment only. In 2006, a large randomized clinical trial showed that use of salmeterol was associated with an increase in asthma-related deaths (when added to usual asthma therapy). The risk appears to be higher in African-American patients. Adverse effects include immediate hypersensitivity reactions, headache, hypertension, and neuromuscular and skeletal pain. Salmeterol should never be given more than twice daily nor should the maximum daily dose (one puff twice daily) be exceeded. It is available as a powder for inhalation either alone (Serevent Diskus) or combined with a corticosteroid (Advair). The long-acting inhalers, including salmeterol, are not to be used alone, but in combination with other drugs such as the inhaled corticosteroids. Advair (salmeterol and fluticasone) is a very popular inhaler for COPD. Symbicort, a newer inhaler consisting of the corticosteroid budesonide and the bronchodilator formoterol, is similar to Advair.



Anticholinergics


Currently there are two anticholinergic drugs used in the treatment of COPD: ipratropium (Atrovent) and tiotropium (Spiriva).


Mechanism of Action and Drug Effects


On the surface of the bronchial tree are receptors for acetylcholine (ACh), the neurotransmitter for the parasympathetic nervous system (PSNS). When the PSNS releases ACh from its nerve endings, it binds to the ACh receptors on the surface of the bronchial tree, which results in bronchial constriction and narrowing of the airways. Anticholinergic drugs block these ACh receptors to prevent bronchoconstriction. This indirectly causes airway dilation. Anticholinergic agents also help reduce secretions in COPD patients.


Indications


Because their actions are slow and prolonged, anticholinergics are used for prevention of the bronchospasm associated with chronic bronchitis or emphysema and not for the management of acute symptoms.


Contraindications


The only usual contraindication to the use of bronchial anticholinergic drugs is drug allergy, including allergy to atropine or to soy lecithin (found in some of the inhalational formulations), or allergy to related food products such as peanut oils, peanuts, soybeans, and other legumes (beans). There have been reported cases of severe anaphylactic reactions to ipratropium inhalers in patients with peanut allergy, and such use is to be avoided. Caution is necessary in patients with acute narrow-angle glaucoma and prostate enlargement.


Adverse Effects


The most commonly reported adverse effects of ipratropium and tiotropium therapy are related to the drugs’ anticholinergic effects and include dry mouth or throat, nasal congestion, heart palpitations, gastrointestinal (GI) distress, urinary retention, increased intraocular pressure, headache, coughing, and anxiety. Ipratropium is classified as a pregnancy category B drug; tiotropium is classified as pregnancy category C.


Drug Interactions


Possible additive toxicity may occur when anticholinergic bronchodilators are taken with other anticholinergic drugs.


Dosages


For dosage information on anticholinergic drugs, see the table on p. 593.


Drug Profile


ipratropium


Ipratropium (Atrovent) is the oldest and most commonly used anticholinergic bronchodilator. It is pharmacologically very similar to atropine (see Chapter 21). It is available both as a liquid aerosol for inhalation and as a multidose inhaler; both forms are usually dosed twice daily. Tiotropium (Spiriva) is a similar drug but is formulated for once-daily dosing. Many patients also benefit from taking both a beta2 agonist and an anticholinergic drug, with the most popular combination being albuterol and ipratropium. Although many patients receive the two drugs separately, two combination products are available containing both of these drugs: Combivent (an MDI) and DuoNeb (an inhalation solution).


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May 9, 2017 | Posted by in NURSING | Comments Off on Respiratory Drugs

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