Nasal Decongestant Notes PDF

Overview of Nasal Congestion and Contributing Factors Patients who have nasal congestion may complain of reduced nasal airflow, a sense of fullness, stuffiness, or obstruction.1,2 Mucosal inflammation is the underlying cause of nasal congestion in allergic rhinitis and rhinosinusitis.1 Nasal...

Overview of Nasal Congestion and Contributing Factors Patients who have nasal congestion may complain of reduced nasal airflow, a sense of fullness, stuffiness, or obstruction.1,2 Mucosal inflammation is the underlying cause of nasal congestion in allergic rhinitis and rhinosinusitis.1 Nasal mucosa can become inflamed due to increased venous blood flow and engorgement, increased nasal secretions, and nasal tissue edema. Nasal congestion caused by mucosal inflammation is a common symptom of allergic rhinitis, rhinosinusitis, and nasal polyposis. Additionally, in patients with obstructive sleep apnea and baseline allergic rhinitis, nasal congestion has been found to worsen or not improve with continuous positive airway pressure (CPAP) use.3 *Allergic Rhinitis* Allergic rhinitis is the most common atopic condition in the United States and affects from 14% to 60% of the population. 2,4 One study reported that 60% of those who reported symptoms of allergic rhinitis most frequently experienced nasal congestion every day or on most days.2 In 2003, researchers reported that the total direct medical cost of allergic rhinitis in the United States was \$3.4 billion.5 In a survey of more than 8000 employees in the United States, allergic rhinitis was reported by 55% as having experienced symptoms on an average of 52.5 days per year. Due to these symptoms, employees missed 3.57 days of work per year and were unproductive for 2.3 hours during the working day if they were experiencing symptoms; this results in a mean productivity loss per employee of \$518. A national survey done in 2006, Allergies in America, sought to better understand the burden of allergies on the American population.2 In this survey of 2500 patients, 80% reported nasal congestion to be an extremely or moderately bothersome symptom of allergic rhinitis. Patients with allergic rhinitis may also have fatigue, mood changes, depression, anxiety, and impairment of cognitive function, all of which can have a significant impact on quality of life.5 However, when patients with allergic rhinitis are using medications for their symptoms such as nonsedating antihistamines, intranasal corticosteroids, and others, they reported improvement in their health-related quality of life. Nasal congestion is frequently a predominant symptom of allergic rhinitis and is due to both the early- and late-phase allergic inflammatory response.1 In a patient with allergic rhinitis, when an antigen encounters nasal mucosa, a crosslinking of immunoglobulin E (IgE) receptors on mast cells occurs. The mast cells then degranulate, which releases histamine and proteases. Early-phase proinflammatory molecules are released including leukotrienes, prostaglandins, tumor necrosis factor (TNF)-α, and interleukin (IL)-4. This leads to swelling, edema, and fluid secretion that causes congestion, among other nasal symptoms. The cellular infiltration of the late-phase inflammatory response causes continued swelling and edema, worsening nasal congestion.1 Inflammatory cells responsible for this reaction include eosinophils, neutrophils, basophils, mast cells, and lymphocytes. In patients with allergic rhinitis, the infiltration of eosinophils has been shown to have a significantly negative correlation on nasal airflow. Unfortunately, as the allergy season progresses, this cellular infiltration primes the mucosa for further antigen exposure and an increased response to it ensues, which means symptoms worsen on continued exposure. The actions of TNF-α, cell adhesion molecules, proinflammatory interleukins, as well as IgE synthesis and eosinophil and basophil priming lead to inflammation, venous engorgement, nasal hyperreactivity, and congestion. There are also forms of nonallergic rhinitis that are not IgE mediated, such as infectious rhinitis, vasomotor rhinitis, nonallergic rhinitis with eosinophilia syndrome, and hormonal rhinitis, which is caused by pregnancy or menstrual irregularities. 1 Nasal congestion is also common in these forms of rhinitis, particularly in pregnancy-related rhinitis. *Rhinosinusitis* Inflammation of the mucosa of the nasal passages and paranasal sinuses is referred to as rhinosinusitis.1 Rhinosinusitis can be caused by infectious and noninfectious as well as immunologic and nonimmunologic inflammation. The most common source of rhinosinusitis is viral infection, or the common cold. Research has shown that the viral infection itself is what stimulates inflammatory pathways that prolong symptoms even after viral replication has stopped. Microorganisms are largely responsible for acute rhinosinusitis, which has a symptom duration of fewer than 4 weeks.2 Similar to allergic rhinitis, proinflammatory cytokines play a large role in causing congestion as a symptom in rhinosinusitis. 1 In addition, kinin levels are significantly increased in patients with viral rhinosinusitis. These kinins cause vascular leakage and engorgement, or overfilling, of blood vessels, as well as stimulate afferent nerves in nasal mucosa, which leads to hyperresponsiveness. In an acute viral upper respiratory infection such as this, TNF-α and proinflammatory cytokines are elevated, and there is an increased infiltration of neutrophils and T cells, which causes the inflammation and venous response that leads to congestion. Acute rhinosinusitis is caused frequently by the common cold, which is one of the most common 5 illnesses in the United States, with 1 billion cases annually.6 Sales of medications to treat colds have been increasing steadily since 2020, and account for \$11.4 billion spent in 2022.7 Adults experience an average of 2-3 colds per year, and children experience 6 or more.6 This results in missed work and school days, and loss of productivity. A study of 374,799 employees over 6 large employers determined that rhinosinusitis was one of the top 10 most costly conditions, with the majority of costs related to medical expenditures, and 41% of the costs related to work absence.2 Chronic rhinosinusitis (CRS) is characterized by symptoms including nasal blockage, nasal obstruction, congestion, nasal discharge with facial pain, and reduction of smell.8 CRS, which has a symptom duration of 12 weeks or longer, may not be caused by an infectious source.1,2 Rhinosinusitis can also be the result of allergic and immunologic causes and can be a risk factor for acute bacterial rhinosinusitis.1 It is estimated that CRS affects more than 12% of the US population.9 Chronic congestion can also cause sleep issues including sleep-disordered breathing, 84 PHARMACYTIMES.ORG JULY 2023 sleep fragmentation, reduced sleep time, reduced sleep quality, and as a result, daytime sleepiness and fatigue.2 *Nasal Polyposis* Nasal polyposis is a chronic inflammatory disease of the upper airway that affects about 4% of the population.1 While the possible causes of nasal polyposis are not clear, it is suggested that chronic infection, aspirin intolerance, trapping of pollutants, epithelial destruction or cell defects, or inhalant or food allergies could be contributing factors. Nasal polyps are commonly formed as a result of chronic inflammatory rhinosinusitis.2 Polyps, which are small sacs filled with cellular fluid, form in the middle meatus and originate from the nasal mucous membrane of the ostia, clefts, and recesses from the paranasal sinuses. The polyps cause nasal blockage because they hang down in the nasal passages and swing back and forth, affecting airflow. Patients with nasal polyposis will have symptoms such as nasal obstruction, nasal discharge, and impairment of sense of smell. Similar to nasal congestion caused by allergic rhinitis and rhinosinusitis, inflammation processes causing edema in the nasal passages lead to congestion in nasal polyposis.1 Eosinophils and related mediators are highly present in allergic and nonallergic nasal polyposis. Chronic rhinosinusitis and nasal polyposis are differentiated by their T-cell response patterns, and Staphylococcus aureus enterotoxins have also been shown to play a role in the pathophysiology of nasal polyposis. An estimated 30 million Americans have chronic rhinosinusitis, and one-third of these patients may have nasal polyposis.10 Results of a Harris on Demand survey conducted in 2021 indicated that of the 529 patients with chronic congestion (occurring for 3 months or more in the past year), nearly 25% endorsed congestion every day, more than half have headaches regularly, and almost half said it impacts their ability to smell or taste food. About 60% of respondents stated that congestion impacts their ability to get a good night's sleep, and one-third feel fatigued as a result of their sleep troubles. Overall, 85% of the respondents stated that congestion negatively impacts their daily activities. STAR\* What is the difference between direct- and indirectacting decongestants? **\*S = Stop; T = Think; A = Assess; R = Review** Treatment of Nasal Congestion Nasal congestion is commonly treated using decongestants. Decongestants are sympathomimetics, which work by stimulating alpha receptors to constrict blood vessels, decreasing vessel engorgement and mucosal edema.6 Direct-acting decongestants work by binding directly to adrenergic receptors. Indirect-acting decongestants such as ephedrine displace norepinephrine from storage vesicles in prejunctional nerve terminals. As stored neurotransmitter is depleted, tachyphylaxis, or diminished response to continued exposure of the neurotransmitter, can develop. Mixed decongestants have both direct and indirect activity. The action of commonly used decongestants is shown in TABLE 1.6 Decongestants are useful in treating both short- and mediumterm congestion; however, their adverse effects often limit their use in larger populations.11 Oral decongestants' sympathomimetic activity causes cardiovascular stimulation and adverse effects such as elevated blood pressure, tachycardia, palpitation, and arrhythmia.6 They can also cause central nervous system stimulation, which can lead to restlessness, insomnia, anxiety, tremors, fear, or hallucinations. Adrenergic stimulation of decongestants can exacerbate certain disease states such as hypertension, coronary heart disease, ischemic heart disease, diabetes mellitus, hyperthyroidism, and elevated intraocular pressure. Additionally, due to their α-adrenergic agonism, these drugs should not be used in patients with prostate disease because they may worsen restricted urinary flow or cause urinary retention.11 Topical intranasal decongestants are not well absorbed in the nasal mucosa, and do not carry many systemic adverse effects.6,11 Adverse effects experienced are usually due to the propellant, vehicle, or the device itself, and include burning, stinging, or dryness. *Oxymetazoline* Oxymetazoline is the longest acting and most widely available of the topical decongestants. On average, it works within 25 seconds after application to reduce edema and inflammation by stimulating α-adrenergic receptors in the arterioles of the nasal mucosa, producing vasoconstriction.12,13 A study done in 2017 with patients with acute rhinitis confirmed that oxymetazoline 0.05% nasal spray relieved congestion symptoms **TABLE 1.** ACTION OF DECONGESTANTS6 **Drug name Route Type** Phenylephrine Oral Direct Pseudoephedrine Oral Mixed Oxymetazoline Topical -- nasal Direct Phenylephrine Topical -- nasal Direct PHARMACYTIMES.ORG 85 JULY 2023 www.**pharmacytimes.**org for up to 12 hours after a single dose.14 As mentioned previously, the sympathomimetic activity of decongestants makes it so they should be avoided in patients with certain comorbidities. However, given that intranasal oxymetazoline is poorly absorbed and therefore not distributed systemically, it is best to use caution in patients with cardiovascular disease, diabetes, thyroid disease, and prostate disease.6 Patients with these concurrent disease states should be stable and well controlled, and they should consult their provider before starting an intranasal decongestant. Intranasal oxymetazoline can cause temporary burning, stinging, increased nasal discharge, dryness of the nasal mucosa, and sneezing.12 The manufacturer does not list any serious adverse effects in the product labeling, as the incidence is low when patients use oxymetazoline at therapeutic doses. Intranasal oxymetazoline can however occasionally cause systemic sympathomimetic effects such as hypertension, nervousness, nausea, dizziness, headache, insomnia, palpitations, or reflex tachycardia.12 As oxymetazoline is not absorbed systemically, there are no drug-drug interactions; however, patients taking monoamine oxidase inhibitors are advised to avoid concurrent use. Several products that all contain oxymetazoline exist on the market under different brand names. Some products have a no-drip formula that keeps the spray from going back down the patient's throat or out their nostril. Some products made under Afrin and Vicks are formulated with moisturizers to keep the nasal passages from becoming dry and irritated. Additionally, oxymetazoline sprays made by Vicks and Mucinex also have formulations that include menthol to provide a cooling feeling to the nasal passages. Available brand name formulations and dosing are shown in TABLE 2.6,15-21 Congestion in children, whether related to allergic rhinitis or acute viral rhinosinusitis, can be very difficult to manage. While intranasal phenylephrine is available in a concentration approved for children aged 2 years to younger than 6, it is dosed every 4 hours, which is not ideal. The long-acting nature of oxymetazoline is preferred in particular for congestion that occurs at night; it can easily be used right before bedtime and should last through the night so the child can get a good night's sleep. Afrin now has a product containing oxymetazoline 0.025% for children aged 2 years to younger than 6, which can be given as 2 or 3 sprays in each nostril every 10 to 12 hours as needed, no more than 2 doses in 24 hours. Adverse effects of this product do not differ from the 0.05% formulation, and the onset and duration of action are similar. In 2012, the FDA published Drug Safety Communication regarding the adverse effects of accidental ingestion of decongestant eye drops and intranasal sprays that contained tetrahydrozoline, oxymetazoline, and naphazoline.22 No deaths were reported from these cases; however, the accidental ingestion by children under 5 of these products required hospitalization and resulted in coma, decreased heart rate, and sedation. Even amounts as small as 1 to 2 milliliters can result in adverse effects such as nausea, vomiting, drooling, hypotension, hyperthermia, and lethargy.6 All intranasal decongestants and eye drops come in child-resistant packaging, but patients should always be reminded to keep these products away from children and to call the Poison Help Line (800-222-1222) in case of accidental ingestion. **TABLE 2.** AVAILABLE OXYMETAZOLINE FORMULATIONS6,15-21 **Brand name Active ingredient Adult dosing Children 6 to \