Chapter 13

1. Chapter 13 Upper Respiratory Agents

2. Drug Overview • Decongestants • Oral: pseudoephedrine, phenylephrine • Topical nasal: phenylephrine, oxymetazoline • Antihistamines • Sedating • ethanolamine: diphenhydramine; clemastine fumarate • alkylamine: chlorpheniramine maleate

3. Drug Overview • Antihistamines • Low-sedating • piperadine: cetirizine HCl • Nonsedating • fexofenadine HCl, loratadine HCl, desloratadine • Intranasal • azelastine

4. Drug Overview • Intranasal Steroids • triamcinolone acetonide, beclomethasone dipropionate, fluticasone propionate • Intranasal Mast Cell Stabilizer • cromolyn sodium • Leukotriene Receptor Antagonist • montelukast sodium

5. Drug Overview • Antitussives • Narcotic: codeine phosphate • Nonnarcotic: dextromethorphan HBr, benzonatate • Expectorants • guaifenesin

6. Indications • Oral Decongestants • Nasal congestion caused by the common cold, hay fever, or other upper respiratory allergies • Nasal congestion associated with sinusitis and eustachian tube congestion

7. Indications • Topical Nasal Decongestants • Symptomatic relief of nasal and nasopharyngeal mucosal congestion caused by the common cold, sinusitis, hay fever, or other upper respiratory allergies • Adjunctive therapy of middle ear infection by decreasing congestion around the eustachian ostia • Relief of ear block and pressure pain during air travel

8. Indications • Antihistamines • Symptomatic relief of symptoms associated with perennial and seasonal allergic rhinitis, vasomotor rhinitis, and allergic conjunctivitis; temporary relief of runny nose and sneezing caused by the common cold • Skin: Allergic and nonallergic pruritic symptoms; mild, uncomplicated urticaria and angioedema • Amelioration of allergic reactions to blood or plasma, dermatographism, and adjunctive therapy in anaphylactic reactions

9. Indications • Intranasal Steroids • Vasomotor rhinitis and relief of symptoms of seasonal or perennial rhinitis when effectiveness of antihistamines or tolerance to treatment develops • Intranasal Mast Cell Stabilizer • Prevention and treatment of allergic rhinitis • Leukotriene Receptor Antagonists • Treatment of allergic rhinitis and perennial allergic rhinitis

10. Indications • Antitussives • Narcotic antitussives • Codeine for suppression of cough induced by chemical or mechanical respiratory tract irritation • Nonnarcotic antitussives • Dextromethorphan HBr (Robitussin) for suppression of nonproductive cough • Benzonatate (Tessalon Perles) for symptomatic relief of cough • Expectorants • Guaifenesin may provide symptomatic relief of respiratory conditions characterized by productive or nonproductive cough

11. Mechanism of Action • Decongestants • Sympathomimetic amines that act to stimulate α-adrenergic receptors of vascular smooth muscle and cause vasoconstriction • Nasal decongestion, contraction of gastrointestinal and urinary sphincters, pupil dilation, and decreased pancreatic β-cell secretion • Pseudoephedrine also has β-adrenergic properties that cause relaxation of the bronchi

12. Mechanism of Action • Decongestants (cont’d) • Topical application of decongestants to the nasal mucous membranes causes vasoconstriction • Promotes drainage and improves breathing through the nasal passages • These inhaled agents produce reduced systemic effects compared with oral preparations

13. Mechanism of Action • Antihistamines • Compete for histamine at H1 receptor sites and are used to treat IgE-mediated allergy • Helpful in treating allergic rhinitis and urticaria in most, but not all, patients • Antagonize the pharmacologic effects of histamine • Do not inactivate histamine or block histamine release, antibody production, or antigen–antibody interactions • Have anticholinergic, antipruritic, and sedative effects to a varying degree • Azelastine is a topical antihistamine nasal spray with few adverse systemic side effects that is used to treat allergic and vasomotor rhinitis

14. Mechanism of Action • Intranasal Steroids • Potent glucocorticoid and weak mineralocorticoid activity • Inhibit cells, including mast cells, eosinophils, neutrophils, macrophages, lymphocytes, and mediators such as histamine, leukotrienes, and cytokines • Exert direct local antiinflammatory effects with minimal systemic effects • Effectively control the four major symptoms of allergic rhinitis—rhinorrhea, congestion, sneezing, and nasal itch • Helpful in managing moderate to severe disease and used to treat both seasonal and perennial allergic rhinitis • Must be used consistently on a daily basis for effectiveness; maximum effects may not be noted for several days to weeks

15. Mechanism of Action • Intranasal Mast Cell Stabilizers • Inhibits Cromolyn sodium is an OTC intranasal mast cell stabilizer that is used as a preventive agent taken in advance of allergen exposure • sensitized and mast cell degranulation that occurs after exposure to specific antigens • Inhibits the release of mediators, histamine, and SRS-A from the mast cell; inhibits calcium from entering the mast cell, resulting in the prevention of mediator release • Effective in reducing rhinorrhea, sneezing, and nasal itching, but it has minimal effect on nasal congestion • Must be taken properly as a nebulized aerosol, inhaled through the mouth, or swallowed orally four to six times a day; its effects may not be seen for 4 to 6 weeks to months

16. Mechanism of Action • Leukotriene Receptor Antagonists • Causes inhibition of airway cysteinyl leukotriene receptors (CysTL), which are products of arachidonic acid metabolism and are released from mast cells and eosinophils • The CysTL type 1 receptor is found in airway smooth muscle cells, airway macrophages, and proinflammatory cells such as eosinophils and myeloid stem cells • CysTL are released from the nasal mucosa after allergen exposure and are associated with symptoms of allergic rhinitis

17. Mechanism of Action • Antitussives • Codeine and dextromethorphan both act centrally by acting on the cough center of the medulla to suppress cough • Dextromethorphan is the d-isomer of codeine; it lacks the analgesic and addictive properties of codeine • Not as effective as codeine in depressing the cough reflex • Benzonatate anesthetizes stretch receptors in the respiratory passages, reducing the cough reflex at its source

18. Mechanism of Action • Expectorants • Increase respiratory tract fluid secretions and help to loosen bronchial secretions by reducing adhesiveness and tissue surface tension • Increase the efficacy of the mucociliary mechanism in removing accumulated secretions from the upper and lower airways • Guaifenesin is classed as questionably effective in some studies

19. Treatment Principles • Standardized Guidelines • Upper respiratory illness in children and adults from the Institute for Clinical Systems Improvement (ICSI) • www.guideline.gov/algorithm/5564/NGC-5564_1.html • ACCP evidence-based clinical practice guidelines for cough and the common cold • www.guideline.gov/summary/summary.aspx?doc_id=8654&nbr=004819

20. Treatment Principles • Evidence-Based Recommendations • According to randomized controlled trials (RCTs) in allergic rhinitis, oral antihistamines are used first in rhinitis and have been found to help control itching, sneezing, rhinorrhea, and stuffiness in most patients but do not alleviate ocular symptoms • Nasal corticosteroids are indicated for patients who do not respond to antihistamines and are considered the most potent medication for treatment of rhinitis

21. Treatment Principles • Evidence-Based Recommendations (cont’d) • Nasal cromolyn is less effective than nasal corticosteroids • Intranasal antihistamines are effective in treating nasal symptoms of seasonal, perennial, and vasomotor rhinitis but offer no benefit over conventional treatment • Oral decongestants decrease nasal mucosal swelling, and this reduces nasal congestion

22. Treatment Principles • Cardinal Points of Treatment • Upper respiratory illness • Hand washing is the most effective way to prevent the spread of viral upper respiratory illness • It is important to recognize the signs and symptoms of serious illness in viral upper respiratory infection and allergic rhinitis • Do not treat cold symptoms with aspirin-containing products for anyone younger than the age of 21 • Do not use cold or cough medications for children younger than 6 months

23. Treatment Principles • Cardinal Points of Treatment (cont’d) • Upper respiratory illness (cont’d) • Avoid acetaminophen in patients with liver dysfunction • In adults, evidence suggests that zinc gluconate may decrease the duration of a cold if started within 24 hours of onset; however, adverse reactions, including nausea and bad taste, may limit its usefulness • Findings in the medical literature do not support the use of echinacea in preventing VURI

24. Treatment Principles • Cardinal Points of Treatment (cont’d) • Allergic rhinitis • Allergy testing is rarely helpful in diagnosing allergic rhinitis but may be useful in patients with multiple allergen sensitivities • Controversy regarding the use of medication vs. immunotherapy is ongoing • Risk–cost analyses have not been performed; however, patients with moderate to severe perennial allergies may benefit most from immunotherapy

25. Treatment Principles • Cardinal Points of Treatment (cont’d) • Cough • Patients with cough associated with VURI can be treated with a first-generation antihistamine/ decongestant combination preparation • Naproxen also can be used to help decrease cough • Newer-generation, nonsedating antihistamines are ineffective in reducing cough and should not be used • Ipratropium bromide for cough due to URI or bronchitis

26. Treatment Principles • Cardinal Points of Treatment (cont’d) • Cough (cont’d) • The current guideline supports the use of codeine only in chronic bronchitis and not in cough due to URI • Peripheral and central cough suppressants have limited efficacy in cough due to URI • OTC combination cold medications, other than antihistamine/decongestant combinations, and preparations that contain zinc are not recommended for acute cough due to the common cold

27. Treatment Principles • Nonpharmacologic Treatment • Rest • Increased fluids • Identification of environmental precipitants • Implement strategies designed to reduce these factors • Normal saline nasal sprays or nasal irrigation, twice daily, may help reduce postnasal drip, sneezing, and congestion

28. Treatment Principles • Pharmacologic Treatment • Mild, intermittent symptoms: Antihistamine, preferably nonsedating, or a decongestant • If the patient is unable to take an oral antihistamine, consider the use of a nasal antihistamine, intranasal cromolyn, or a leukotriene receptor antagonist • Moderate, frequent symptoms: Regular- to high-dose intranasal corticosteroid • Add an oral or nasal antihistamine and decongestant if necessary

29. Treatment Principles • Pharmacologic Treatment (cont’d) • Moderate, persistent symptoms: Combination regimen consisting of intranasal corticosteroids plus a nonsedating or intranasal antihistamine and decongestant if necessary • Severe symptoms: Combination regimen consisting of a nonsedating antihistamine with or without a decongestant and intranasal corticosteroid • Consider the use of an oral steroid for 5 days and the use of oxymetazoline as needed for no longer than 3 days

30. Treatment Principles • Pharmacologic Treatment (cont’d) • Decongestants • Very effective • Decongestants should be used with caution in patients with hypertension, cardiovascular and peripheral vascular disease, hyperthyroidism, diabetes mellitus, prostatic hyperplasia, urinary retention, and increased intraocular pressure • They are contraindicated in patients with mitral valve prolapse and cardiac palpitations • They also have many side effects that can limit their use, particularly in the elderly

31. Treatment Principles • Pharmacologic Treatment (cont’d) • Antihistamines • Often used alone or in combination with decongestants and expectorants to relieve symptoms associated with perennial and seasonal allergies with associated rhinitis, vasomotor rhinitis, allergic conjunctivitis, and cold symptoms such as sneezing and runny nose • They also are used to relieve allergic and nonallergic pruritic symptoms, to alleviate mild urticaria and angioedema, for prophylaxis against allergic reactions to blood or plasma products, and as adjunctive therapy in anaphylactic reactions • Certain antihistamines also have antiemetic effects and are used for nausea, vomiting, vertigo, motion sickness

32. Treatment Principles • Pharmacologic Treatment (cont’d) • Antihistamines • Use in the treatment of cold symptoms is controversial • Antihistamines are best used to treat allergic symptoms such as rhinorrhea; watery, itchy eyes; postnasal drainage; and sneezing • Decongestants are preferred as treatment of cold symptoms, such as nasal congestion caused by swollen nasal membranes

33. Treatment Principles • Pharmacologic Treatment (cont’d) • Antihistamines • Not recommended to treat lower respiratory tract symptoms, including asthma, because some of their anticholinergic effects may cause thickening of respiratory secretions and may impair expectoration • Several evidence-based reports, however, indicate that antihistamines can be safely used in asthmatic patients with severe perennial allergies without causing exacerbation of asthma • First generation vs. second generation • OTC preparations

34. Treatment Principles • Pharmacologic Treatment (cont’d) • Intranasal steroids • The most effective agents for the management of allergic rhinitis because of their direct reduction of nasal inflammation and their ability to reduce nasal hyperreactivity • Should be used for at least 1 month before a decision is made as to whether they are effective • Can be used with asthmatic patients and with those who have comorbid nasal polyposis • Intranasal steroids may help shrink nasal polyps

35. Treatment Principles • Pharmacologic Treatment (cont’d) • Intranasal mast cell stabilizers (cromolyn) • Particularly effective in patients with intermittent allergies, especially when determined to be prevalent during only one season of the year • Should be started 3 to 4 weeks before a peak allergy season occurs • Their effect on the nose is short acting and makes compliance more difficult in that several doses are needed per day • Intraocular agents also are very effective • Continue treatment throughout exposure

36. Treatment Principles • Pharmacologic Treatment (cont’d) • Leukotriene receptor antagonists • Used for the relief of symptoms of allergic rhinitis in • Adults (particularly those with asthma) • Pediatric patients, 2 years and older • Adults and pediatric patients 6 months and older with perennial allergic rhinitis • Associated with early-phase allergic symptoms, including sneezing, rhinorrhea, and nasal itching, as well as late-phase reactions such as congestion, sneezing, and rhinorrhea • Antileukotriene use often is offered in combination with other therapies, especially when nasal congestion is not ameliorated by other modalities

37. Treatment Principles • Pharmacologic Treatment (cont’d) • Antitussives • Antitussives are used to control or suppress cough caused by respiratory tract irritation, colds, or allergies • It is important to determine the underlying disorder that is causing the cough, particularly to rule out serious causes of cough • Antitussives should not be given in conditions in which retention of respiratory secretions may be harmful • In general, a cough should not be suppressed • If a patient is having a nonproductive cough that is causing muscle pain or is interfering with sleep, it should be suppressed

38. Treatment Principles • Pharmacologic Treatment (cont’d) • Expectorants • Used for the symptomatic relief of a dry, nonproductive cough associated with respiratory tract infection • Expectorants often are used when the patient insists on a cough remedy when cough suppression is not indicated or because the patient believes the effect to be beneficial • Fluid intake—up to a gallon of water a day if people who do not have a fluid restriction—is very important

39. How to Monitor • Decongestants • Monitor for symptoms of CNS stimulation in the oral route • Monitor topical application for frequency of use • Antihistamines • Relief of excessive drowsiness

40. How to Monitor • Intranasal Steroids • Monitor for development of infection in the nose or sinus • During long-term use, monitor for changes in nasal mucosa, such as growth of polyps

41. Patient Variables • Geriatrics • Decrease dosage of antihistamine • Prescribe antitussive codeine with caution • Pediatrics • Avoid sustained-release decongestants • Antihistamines may diminish mental alertness or paradoxical excitation • Seizure risk in high doses

42. Patient Variables • Pediatrics (cont’d) • Use of intranasal corticosteroids in prepubescent children poses a potential risk of growth suppression • Studies with beclomethasone dipropionate used twice daily have shown a significant decrease in growth velocity. This has not been shown with other intranasal steroids (mometasone furoate monohydrate, budesonide, or fluticasone propionate)

43. Patient Variables • Pediatrics (cont’d) • Codeine is contraindicated in premature infants • Give to infants and small children with extreme caution, and monitor the dosage carefully • Caution is recommended when expectorants are administered to children up to 12 years of age with persistent or chronic cough, asthma, or cough that is accompanied by excessive mucus

44. Patient Variables • Pregnancy and Lactation • Decongestant products should not be used in nursing mothers • Category B: Antihistamines (azatadine, cetirizine, chlorpheniramine, clemastine, cyproheptadine, dexchlorpheniramine, diphenhydramine, loratadine) and leukotriene receptor antagonists • Category C: Antihistamines (brompheniramine, carbinoxamine, desloratadine, fexofenadine, hydroxyzine, pheniramine, promethazine, triprolidine), intranasal steroids, antitussives (codeine), and expectorants • Safe use of antihistamines in pregnancy has not been established

45. Patient Variables • Pregnancy and Lactation (cont’d) • Antihistamines: Do not use during the third trimester of pregnancy; newborn and premature infants may have severe reactions • Because of the higher risk of adverse effects in infants, antihistamine therapy generally is contraindicated in nursing mothers

46. Patient Education • Decongestants • Reduce consumption of caffeine-containing beverages • Use medication for only 2 to 3 days, then stop so a rebound in symptoms can be prevented • May continue to use treatment-rest cycles while symptomatic

47. Patient Education • Antihistamines • Antihistamines are used to treat allergy symptoms and should not be used to treat URIs, including colds and sinusitis • Do not use alcohol, sleeping pills, sedatives, or tranquilizers while taking antihistamines • Patients should avoid driving a car or performing hazardous tasks until the effects of medication are known

48. Patient Education • Antihistamines (cont’d) • Antihistamines should be stored in a tightly closed container in a cool, dry place away from heat and sunlight and out of the reach of children • Some antihistamines may cause stomach upset; they should be taken with food • Antihistamines may cause photosensitivity; patients should avoid prolonged sunlight exposure • Do not crush or chew sustained-release preparations

49. Patient Education • Intranasal Steroids • Use patient information provided with product on how to use nebulizer, inhaler • Do not exceed recommended dosage • Clear secretions from nasal passages before using; use decongestants if necessary • Effects are not immediate; results require regular use and may take up to 7 days

50. Patient Education • Intranasal Mast Cell Stabilizers (cromolyn) • Clear the nasal passages before administering the spray, and inhale through the nose during administration • Follow the information provided with the product for correct administration of nebulizer, inhaler, or oral ampules of medicine • Do not discontinue therapy abruptly without consulting a provider