Drugs for allergic rhinitis, cough, and colds

The drugs addressed in this chapter are given to alleviate symptoms of common respiratory disorders. Our principal focus is allergic rhinitis.

Drugs for allergic rhinitis

Allergic rhinitis is an inflammatory disorder that affects the upper airway, lower airway, and eyes. Major symptoms are sneezing, rhinorrhea (runny nose), pruritus (itching), and nasal congestion (caused by dilation and increased permeability of nasal blood vessels). In addition, some patients experience conjunctivitis, sinusitis, and even asthma. Symptoms are triggered by airborne allergens, which bind to immunoglobulin E (IgE) antibodies on mast cells, and thereby cause release of inflammatory mediators, including histamine, leukotrienes, and prostaglandins. Allergic rhinitis is the most common allergic disorder, affecting 20 to 40 million Americans (10% to 30% of adults and up to 40% of children).

Allergic rhinitis has two major forms: seasonal and perennial. Seasonal rhinitis, also known as hay fever or rose fever, occurs in the spring and fall in reaction to outdoor allergens, including fungi and pollens from weeds, grasses, and trees. Perennial (nonseasonal) rhinitis is triggered by indoor allergens, especially the house dust mite and pet dander.

Several classes of drugs are used for allergic rhinitis (Table 77–1). Principal among these are (1) glucocorticoids (intranasal), (2) antihistamines (oral and intranasal), and (3) sympathomimetics (oral and intranasal). Glucocorticoids and antihistamines are considered first-line therapies. Of the two, glucocorticoids are much more effective. Sympathomimetics are used in conjunction with other agents to help relieve nasal congestion.

TABLE 77–1

Overview of Drugs for Allergic Rhinitis

Drug or Class	Route	Actions	Adverse Effects
Glucocorticoids	Nasal	Prevent inflammatory response to allergens and thereby reduce all symptoms.	Nasal irritation; possible slowing of linear growth in children
Antihistamines	Oral/nasal	Block H₁ receptors and thereby decrease itching, sneezing, and rhinorrhea; do not reduce congestion.	Oral: Sedation and anticholinergic effects (mostly with first-generation agents) Nasal: Bitter taste
Cromolyn	Nasal	Prevents release of inflammatory mediators from mast cells, and thereby can decrease all symptoms. However, benefits are modest.	None
Sympathomimetics	Oral/nasal	Activate vascular alpha₁ receptors and thereby cause vasoconstriction, which reduces nasal congestion; do not decrease sneezing, itching, or rhinorrhea.	Oral: Restlessness, insomnia, increased blood pressure Nasal: Rebound nasal congestion
Anticholinergics	Nasal	Block nasal cholinergic receptors and thereby reduce secretions; do not decrease sneezing, nasal congestion, or postnasal drip.	Nasal drying and irritation
Antileukotrienes	Oral	Block leukotriene receptors and thereby reduce nasal congestion.	Rare neuropsychiatric effects

Approaches to rhinitis management discussed below are based in large part on an evidence-based guideline—The Diagnosis and Management of Rhinitis: An Updated Practice Parameter—released in 2008 by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology.

Intranasal glucocorticoids

The basic pharmacology of the glucocorticoids is discussed in Chapter 72. Consideration here is limited to their use in allergic rhinitis.

Actions and uses.

Intranasal glucocorticoids are the most effective drugs for prevention and treatment of seasonal and perennial rhinitis. For patients with mild to moderate rhinitis, glucocorticoids are the initial treatment of choice. With proper use, over 90% of patients respond. Because of their anti-inflammatory actions, these drugs can prevent or suppress all of the major symptoms of allergic rhinitis: congestion, rhinorrhea, sneezing, nasal itching, and erythema. In the past, intranasal steroids were reserved for patients whose symptoms could not be controlled with more traditional drugs (antihistamines, sympathomimetics, intranasal cromolyn). However, because of their proven safety and superior efficacy, glucocorticoids have now replaced the histamine₁ (H₁) antagonists as the treatment of first choice. Seven glucocorticoids are available (Table 77–2). All appear equally effective.

TABLE 77–2

Some Glucocorticoid Nasal Sprays for Allergic Rhinitis

Drug	Trade Name	Intranasal Bioavailability (%)	Dose/Spray (mcg)	Patient Age (yr)	Initial Dosage (Sprays/Nostril)
Beclomethasone	Beconase AQ	44	42	6–11 12 and older	1 twice daily 1 or 2 twice daily
Budesonide	Rhinocort Aqua	34	32	6–11 12 and older	1 or 2 once daily 1–4 once daily
Ciclesonide	Omnaris	—	50	6 and older	2 once daily
Flunisolide	generic only	49	25	6–13 14 and older	2 twice daily or 1 thrice daily 2 twice or thrice daily
Fluticasone propionate	Flonase	0.5–2	50	4–11 12 and older	1 once daily 2 once daily
Fluticasone furoate	Veramyst	—	27.5	2–11 12 and older	1 once daily 2 once daily
Mometasone	Nasonex	0.1	50	2–11 12 and older	1 once daily 2 once daily
Triamcinolone	Nasacort AQ	46	55	6 and older	1 or 2 once daily

Adverse effects.

Adverse effects are generally mild. The most common are drying of the nasal mucosa and a burning or itching sensation. Sore throat, epistaxis (nosebleed), and headache may also occur.

Systemic effects are possible, but are rare at recommended doses. Of greatest concern are adrenal suppression and slowing of linear growth in children (whether final adult height is reduced is unknown). Systemic effects are least likely with fluticasone and mometasone, which have very low bioavailability (see Table 77–2).

Preparations, dosage, and administration.

Intranasal glucocorticoids are administered using a metered-dose spray device. Benefits are greatest when dosing is done daily, rather than PRN. Full doses are given initially (see Table 77–2). After symptoms are under control, the dosage should be reduced to the lowest effective amount. For patients with seasonal allergic rhinitis, maximal effects may require a week or more to develop. However, an initial response can be seen within hours. For patients with perennial rhinitis, maximal responses may take 2 to 3 weeks to develop. If nasal passages are blocked, they should be cleared with a topical decongestant prior to glucocorticoid administration.

Antihistamines

The antihistamines are discussed at length in Chapter 70. Consideration here is limited to their use in allergic rhinitis.

Oral antihistamines

Oral antihistamines (H₁ receptor antagonists) are first-line drugs for mild to moderate allergic rhinitis. These drugs can relieve sneezing, rhinorrhea, and nasal itching. However, they do not reduce nasal congestion. Because histamine is only one of several mediators of allergic rhinitis, antihistamines are less effective than glucocorticoids. Because histamine does not contribute to symptoms of infectious rhinitis, antihistamines are of no value against the common cold.

For therapy of allergic rhinitis, antihistamines are most effective when taken prophylactically, and less helpful when taken after symptoms appear. Accordingly, antihistamines should be administered on a regular basis throughout the allergy season, even when symptoms are absent.

Adverse effects are usually mild. The most frequent complaint is sedation, which occurs often with the first-generation antihistamines (eg, diphenhydramine), and much less with the second-generation agents (eg, fexofenadine). Accordingly, second-generation agents are clearly preferred. Anticholinergic effects (eg, dry mouth, constipation, urinary hesitancy) are common with first-generation agents, and relatively rare with the second-generation agents.

Dosages for some popular H₁ antagonists are presented in Table 77–3. A more complete list appears in Table 70–2 (Chapter 70).

TABLE 77–3

Some Antihistamines for Allergic Rhinitis

Generic Name	Trade Name	Dosage
Oral Antihistamines
First-Generation (Sedating)
Chlorpheniramine	Chlor-Trimeton Allergy, Chlor-Tripolon, others	Adults and children 12 yr and older: 4 mg q 4–6 h Children 6–11 yr: 2 mg q 4–6 h
Diphenhydramine	Benadryl, others	Adults: 25–50 mg q 4–6 h Children under 10 kg: 12.5–25 mg 3 or 4 times/day
Second-Generation (Nonsedating)
Cetirizine*	Zyrtec, Reactine	Adults and children 6 yr and older: 5 or 10 mg once daily
Levocetirizine	Xyzal	Adults and children 12 yr and older: 5 mg once daily Children 6–11 yr: 2.5 mg once daily
Fexofenadine	Allegra	Adults and children 12 yr and older: 60 mg twice daily or 180 mg once daily
Loratadine	Claritin, Alavert	Adults and children 6 yr and older: 10 mg once daily
Desloratadine	Clarinex, Aerius	Adults and children 12 yr and older: 5 mg once daily
Intranasal Antihistamines
Second-Generation (Nonsedating)
Azelastine*	Astelin, Astepro	Adults and children 12 yr and older: 2 sprays/nostril twice daily Children 5–11 yr: 1 spray/nostril twice daily^†
Olopatadine	Patanase	Adults and children 12 yr and older: 2 sprays/nostril twice daily (665 mcg/spray)