Drugs for Respiratory Tract Disorders



Drugs for Respiratory Tract Disorders



Classification of Drugs for Respiratory Tract Disorders








aAlso budesonide (PULMICORT, RHINOCORT), beclomethasone (QVAR), mometasone (NASONEX), triamcinolone (NASACORT), and ciclesonide (OMNARIS).


bAlso prednisolone, and methylprednisolone.


cAlso lodoxamide (ALOMIDE), and nedocromil (ALOCRIL).


dAlso levalbuterol (XOPENEX), fenoterol (BEROTEC), pirbuterol (MAXAIR), indacaterol (ARCAPTA), and terbutaline.


eAlso loratadine (CLARITIN), and cetirizine (ZYRTEC).




Overview


Disorders of the respiratory tract include a wide range of conditions that can be divided into pulmonary disorders and upper respiratory tract disorders. Pulmonary disorders include asthma, chronic obstructive pulmonary disease (COPD), pneumonia, pulmonary fibrosis, and various other conditions. Upper respiratory tract disorders include allergic rhinitis and microbial infections of the nose, sinuses, and throat. This chapter is concerned primarily with the drugs used in the treatment of asthma, COPD, and rhinitis. Drugs used to treat symptoms of cough and congestion are also discussed in this chapter.



Asthma


Asthma is characterized by airway inflammation and hyperresponsiveness to stimuli that produce bronchoconstriction. These stimuli include cold air, exercise, a wide variety of allergens, and emotional stress (see Box 27-1).



Box 27-1   A Case of Coughing and Wheezing



Case Presentation


A 12-year-old boy is brought to his pediatrician after a recent onset of episodes of coughing, wheezing, and shortness of breath. These episodes have occurred two or three times a week while he was playing outdoors, and they gradually subsided after he came indoors and sat down to rest. The family has a history of allergies to molds and pollens, and the boy has been taking an antihistamine for allergic rhinitis. Examination shows an alert, well-developed boy of normal height and weight who is in no distress. His vital signs and breath sounds are normal except for fine wheezes during forced expiration, and there are no signs of infection. Spirometry tests show a forced expiratory volume in 1 second (FEV1) that is 85% of the predicted value, and the boy’s peak expiratory flow (PEF) variability is 20% (normal <20%). These findings are consistent with a diagnosis of mild asthma, which was probably precipitated by exposure to allergens and by exercise. After discussing treatment options with his parents, the boy is started on a daily dose of montelukast, and an albuterol inhaler will be used to control acute episodes. The patient and his parents receive further instructions and training concerning the use of the inhaler, and he is given prescriptions and scheduled for a follow-up evaluation in 3 weeks to determine the need for additional therapy.



In susceptible persons, exposure to a stimulus triggers the release of substances from mast cells, eosinophils, basophils, neutrophils, and macrophages. Some of these substances, such as histamine, adenosine, bradykinin, and major basic protein, are stored in cell granules. Other substances are formed and immediately released in response to asthmatic stimuli, including lipid mediators derived from arachidonic acid, such as leukotrienes and prostaglandins. All of these substances contribute to inflammation of the airway, edema and desquamation of the bronchial epithelium, and hypertrophy of smooth muscles in the respiratory tract. These chemical mediators also increase the responsiveness of smooth muscles and the permeability of bronchioles to allergens, infectious agents, mediators of inflammation, and other irritants. As a result of these effects, mucus production increases and leads to mucus plugging of the airways, thereby decreasing the ability of the airways to remove noxious substances. As a result, patients develop airway obstruction and must use accessory muscles to breathe.


Airway obstruction in asthma results from a combination of bronchial inflammation, smooth muscle constriction, and obstruction of the lumen with mucus, inflammatory cells, and epithelial debris. Symptoms of obstruction include dyspnea (difficult breathing), coughing, wheezing, headache, tachycardia, syncope, diaphoresis, pallor, and cyanosis. Patients experience a biphasic reduction in pulmonary function, with an early phase that occurs within 10 to 30 minutes of exposure to an allergen and lasts for 2 to 3 hours and then a late phase that occurs 2 to 8 hours after exposure. The late phase is believed to be responsible for inducing and maintaining bronchial hyperreactivity in asthmatic patients. Because of the circadian variation in bronchial responsiveness, some patients have up to an eightfold increase in airway hyperresponsiveness at night, and nearly 70% of asthma-related deaths happen at night.


The drugs used to treat asthma include antiinflammatory drugs and bronchodilators. The pathophysiology of asthma and sites of antiinflammatory drug action are illustrated in Figure 27-1.


image
FIGURE 27-1 Pathophysiology of asthma and sites of antiinflammatory drug action. When allergens activate T cells, cytokine production is stimulated. The cytokines, in turn, trigger the recruitment, activation, and release of a variety of cells and mediators. Glucocorticoids (corticosteroids) inhibit numerous steps in this process, including T-cell activation, cytokine production, eosinophil recruitment and activation, and mast cell migration. Glucocorticoids, cromolyn sodium, and other cromolyn-related drugs all inhibit the release of mediators from mast cells and eosinophils. Cromolyn and related drugs also inhibit eosinophil chemotaxis induced by cytokines and other mediators. Leukotriene inhibitors either block leukotriene receptors or inhibit leukotriene synthesis. IgE, Immunoglobulin E.


Rhinitis


Rhinitis is most frequently caused by allergic reactions to pollens, mold spores, dust mites, and other environmental allergens or by infections with viruses, such as rhinoviruses and other agents of the common cold.


Allergic rhinitis can be seasonal or nonseasonal (perennial), whereas viral rhinitis is an acute, self-limiting condition. Both types of rhinitis are characterized by sneezing, nasal congestion, and rhinorrhea. Nasal pruritus and conjunctivitis are more commonly associated with allergic rhinitis than with viral rhinitis. Malaise, pain, and general discomfort are generally associated with viral rhinitis.


Table 27-1 shows the relative efficacy of various types of respiratory tract drugs, including those used in the treatment of allergic rhinitis and viral rhinitis.




Chronic Obstructive Pulmonary Diseases


COPD includes chronic bronchitis and emphysema. Chronic bronchitis is characterized by a productive cough associated with inflammation of the bronchioles, whereas emphysema is caused by permanent destruction and enlargement of the airspaces distal to the bronchioles. Both conditions result in airway obstruction, dyspnea (difficult breathing), decreased blood oxygen concentrations, and elevated blood carbon dioxide concentrations. Patients with these conditions have abnormal pulmonary function test values, such as a decreased forced expiratory volume in 1 second (FEV1). Smoking and advanced age are the primary risk factors for COPD, and smoking cessation can slow disease progression. Although most of the airway obstruction in COPD is irreversible, a portion of the obstruction is caused by smooth muscle spasm and bronchiolar inflammation, and this portion can be reversed by bronchodilator drugs. Patients with COPD often require long-term oxygen therapy, and antibiotics can be used to treat acute exacerbations caused by bacterial infections.



Antiinflammatory Drugs


Corticosteroids


Corticosteroids (glucocorticoids) are effective in the treatment of a wide variety of inflammatory and other diseases. The discussion here focuses on the use corticosteroids for asthma, allergic rhinitis, and COPD. The pharmacologic properties and clinical use of these drugs are described more completely in Chapter 33.


The recognition that asthma is primarily an inflammatory disease has increased the role of corticosteroids in asthma therapy. For persons with moderate to severe asthma, steroids have become the cornerstone of therapy, and some patients with mild asthma may derive significant benefit from their use as well. Although corticosteroids are the most efficacious antiinflammatory drugs available for the treatment of both asthma and allergic rhinitis (see Table 27-1), they have the potential to cause a number of adverse effects if given systemically. The incidence of adverse effects is markedly reduced when these drugs are given by inhalation, so this route of administration is employed whenever possible. Systemic administration is usually reserved for the treatment of severe asthma or for short-term treatment of severe allergic rhinitis.


Among the steroids available as metered-dose inhalers are beclomethasone, budesonide, fluticasone, and triamcinolone. Beclomethasone and triamcinolone are usually administered three or four times a day, whereas fluticasone and budesonide need to be administered only twice a day. The proper use of metered-dose inhalers requires considerable skill and the use of a spacer device between the mouth and the inhaler. The spacer decreases the amount of drug that is deposited in the mouth and upper airway and facilitates the delivery of the drug to the bronchioles.


As with other antiinflammatory drugs, corticosteroids are primarily used on a long-term basis to prevent asthmatic attacks, rather than to treat acute bronchospasm. The maximal response to steroids usually requires treatment for up to 8 weeks. Corticosteroids can reduce the number and severity of symptoms and decrease the need for β2-adrenoceptor agonists and other bronchodilators.


Adverse effects associated with inhaled corticosteroids are usually mild. Excessive deposition of the drugs in the mouth and upper airway can lead to oral candidiasis (thrush). There has been some concern about the potential for steroids to suppress growth in children. This problem is difficult to evaluate because asthmatic children may have growth disturbances related to their disease. A meta-analysis of 21 studies, however, concluded that inhaled beclomethasone does not cause growth impairment. Another study showed that 95% of children who received inhaled budesonide for an average of 9 years reached their target adult height despite initial growth retardation.


Formulation products combining corticosteroids and long-acting β2-receptor agonists (see later), including fluticasone and salmeterol (ADVAIR), budesonide and formoterol (SYMBICORT), and mometasone and formoterol (DULERA), are often used for the treatment of asthma.



Mast Cell Stabilizers


Cromolyn Sodium





Indications

Cromolyn is administered by inhalation to treat asthma or allergic rhinitis and is available in an ophthalmic solution to treat vernal (seasonal) conjunctivitis. Cromolyn and related compounds are primarily used for the long-term prophylaxis of asthmatic bronchoconstriction and allergic reactions, and they have no role in the treatment of acute bronchospasm. For perennial asthma, the drug is usually given several times a day at regular intervals until symptoms resolve. Improvement can require several weeks, and then the dosage can be reduced to the lowest effective level. For exercise-induced asthma, cromolyn is inhaled 1 hour or less before the anticipated exercise. For allergic rhinitis or vernal conjunctivitis, cromolyn is administered several times a day at regular intervals.


Cromolyn is administered orally before meals and at bedtime to treat systemic mastocytosis, a rare condition characterized by infiltration of the liver, spleen, lymph nodes, and gastrointestinal tract with mast cells. A similar dosage schedule has been used to treat ulcerative colitis and food allergy.

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Jul 23, 2016 | Posted by in PHARMACY | Comments Off on Drugs for Respiratory Tract Disorders

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