Xylometazoline / Otrivin Review Article
Long-lasting relief of nasal congestion
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Nasal Drops and Sprays. Comparative review
Nasal Drops and Sprays are liquid dosage forms available as solutions or suspensions. They are used to produce a local effect on the nasal lining and on rare occasions, for systemic effects (intranasal sprays) such as for the treatment of migraine and nicotine cravings. Usually, nasal preparations are used for local decongestion. Nasal decongestant drops or sprays are used to manage medical conditions like the common colds, flu, or allergic rhinitis, by reducing the clogging of nasal passages. They are used to provide symptomatic relief.
The Common Colds
Colds are respiratory conditions caused by viruses such as those from the Rhinoviridae, Coronaviridae and Picornaviridae families. There are atleast 200 known viruses that cause the common colds, with the majority caused by Rhinoviruses.
The main route for cold transmission is through direct contact with an infected person – shaking hands, being near when an infected person sneezes - or by picking up the virus from contaminated surfaces where cold droplets are left. Viruses can survive outside the body and into surfaces for about three hours. Upon making contact with a healthy person, the virus inoculates itself in the mucosal membrane. This causes a surge of inflammatory mediators which attacks the cold virus, resulting to a cascade of symptoms. The first symptoms felt are scratchy, sore throat, runny nose, watery-itchy eyes, fatigue, sneezing, and general increased secretions of the nose, throat and bronchial tubes. With time, cough appears, and the watery secretions become thick. These symptoms generally last for about ten days.
Why are colds more common in cold seasons? There are three main reasons. First, humidity is low, which is favorable for viral survival in the environment. Second, the cold weather causes the nasal mucosa and linings to dry, making them more susceptible to viral inoculation. Lastly, transmission is higher since people tend to gather, making them more exposed to viruses carried by an infected person.
The good thing about colds is that a single infection provides a lifetime or at least long term immunity. These means that as a person gets older, the fewer colds they get due to the exposure to different viruses before and eventual attainment of immunity.
Though there is wide variety of causative agents, treatment is only for symptomatic relief. This is because colds are benign and self-limiting – the viral infection will eventually resolve with enough rest. Antiviral agents are not needed.
Allergic rhinitis is the inflammation of the nasal mucosal membrane. It occurs when a hypersensitive individual inhales an allergenic material and develops symptoms like itchy sore throat, sneezing, nasal itching, watery nasal secretions, and nasal congestion. When an allergen makes contact with the mucus membranes, the patient elicits an immune response mediated by Immunoglublin E or IgE, which causes the release of inflammatory mediators. Inflammatory mediators include histamine, neutrophil chemotactic factor, eosinophil chomotactic factor, kinins, thromboxanes, platelet-activating factor, and others. These mediators cause the symptoms felt by the patient.
Rhinitis is characterized by either one or more of the following symptoms: congestion, nasal obstruction, rhinorrhea, sneezing, and/or nasal itching. Other symptoms may include sore, scratchy or itchy throat, headaches, facial pain, aural pain, and even sleep disturbances. Allergic rhinitis is a common medical condition (Di Piro, et al., 2008). It is the 6th most common chronic condition in the United States.
According to the Merck Manual, it is a symptom complex which includes two main types, seasonal allergic rhinitis (hay fever) and perennial allergic rhinitis. Seasonal allergic rhinitis occurs during specific season in a year, and includes allergens like pollens that are present during spring, and others. Perennial allergic rhinitis, on the other hand, is an all-year round disease caused by allergens not related to the season, like dusts, animal dander, and others.
The mainstay treatments of allergic rhinitis are antihistamines (histamine being the primary mediator) and corticosteroids (to control immune cells). Aside from that, immediate symptomatic relief is also given to patients, such as topical decongestants.
Topical Decongestants – Nasal Decongestants
Nasal decongestants are very popular agents for use, due to their immediate effects. Results are observed within minutes. Some of the drugs most commonly used are Phenylephrine, Naphazoline, Oxymetazoline, Xylometazoline, Tramazoline and Tetrahydrozoline (Sweetman, 2009). These drugs are classified as ?-adrenergic agonists, used as topical decongestants. Below shows available brand names for these agents.
Brand Names Available: 4-Way, 4-Way Menthol, Afrin 4 Hour Extra Moisturizing, Little Noses Decongestant, Neo-Synephrine Extra Strength Nasal, Neo-Synephrine Mild Nasal, Neo-Synephrine Nasal, Sinex Nasal Spray, Sinex Ultra Fine Mist, Alconefrin-12, Nostril Nasal Decongestant, Rhinall, Nasal Four
Brand Names Available: Privine Oxymetazoline Afrin and other Afrin variations, Allerest 12 Hour Nasal Spray, Duramist Plus, Duration, Four-Way Nasal Spray, Genasal, Neo-Synephrine 12 Hour, Nostrilla, NRS Nasal, NTZ Long Acting Nasal, Oxyfrin, Oxymeta-12, Sinarest Nasal, Sinex Long-Acting, Twice-A-Day, 12 Hour Nasal, Zicam Extreme Congestion Relief, Zicam Sinus Relief, 12 Hour Nasal Decongestant, Neo-Synephrine 12 Hour Extra Moisturizing, Afrin No Drip Severe Congestion, Mucinex Moisture Smart, Mucinex Full Force, Sudafed OM Sinus Congestion and other Sudafed variations, Nasal Mist, Dristan 12-Hour
Brand Names Available: Otrivin, Triaminic Decongestant
Brand Names Available: Muconasal, Rhinospray Eucaliptus, Biciron, Ellatun ?, Ellatun N, Rinogutt, Spray-Tish, Towk
Brand Names Available: Tyzine Nasal
Phenylephrine is a specific ?1-agonist, while the other four are nonselective (both ?1 and ?2) ?-agonists, with a higher preference for ?2. These nonselective agents possess an imidazoline structure.
Mechanism of Action
Colds or allergic rhinitis patients’ frequent complaint is difficulty in breathing, due to airway congestion. Nasal decongestants provide symptomatic relief by reducing the clogging of nasal passages and reducing resistance to airflow. As mentioned, the nasal decongestants belong to the ?-adrenergic agonist drug class.
As such, these agents activate ?-adrenergic receptors found on blood vessels producing vasoconstriction. Specifically, topical nasal decongestants act on the nasal mucosal blood vessels. With these blood vessels constricted, the nasal passages are dilated (Johnson & Hricik, 1993), where an improvement of ventilation, promotion of drainage and improvement of nasal stiffness are all felt (Sweetman, 2009) by the patient. Due to their localized effect, topical decongestants have greater obstruction reduction as compared to the orally administered decongestants (van Cauwenberge, et al., 2000).
Which one is the best to use?
All agents have been proven to be clinically safe and effective. In fact, all of these agents are available as over-the-counter preparations. Regarding which is the best or recommended drug to use, several studies are available that shows the advantages of one agent against the other. However, up to date there is no study that directly compares all of these agents.
All topical decongestants are very effective in providing relief from nasal congestion (van Cauwenberge, et al., 2000). In a study by Hamels and Clement (1994), they compared the efficacy of phenylephrine with xylometazoline in terms of nasal airway resistance (NAR) reduction. They found that xylometazoline, and perhaps the other imidazolines like oxymetazoline and naphazoline, provides a larger reduction in NAR by as much as 33%, and a longer effect for up to 8 hours; phenylephrine on the other hand provides only 17% reduction for 0.5-2 hours. The results of this study holds true for a study made by Carboz et al. (2007), wherein the results they found suggests that agents with higher ?2 preference have better efficacy. Studies made by Andersson and Bende (1984) and Lacroix and Lundberg (1989) all support that the ?2 selective agonists like the imidazolines are more effective.
As mentioned, all of these agents have established their safety in use. Comparing these agents, according to some studies, the selective ?1 agonist phenylephrine is safer to use. In a study by DeBernardis and colleagues (1987), they found that selective ?1 agonists are less likely to induce mucosal damage. Another study has found that mucosal damage involves activation of ?2 receptors – a feature of nonselective agents.
Alpha-adrenergic side effects
Hypertension is a known side effect of ?-adrenergic agent. This is also the basis for the use of these agents in nasal decongestion. But hypertension is not a major concern with these drugs. The vasoconstricting-effects of these agents are localized. Therefore, only the blood vessels of the nasal mucosa are constricted. This local effect reduces the risk of drug-induced hypertension. In fact, according to Pray (2004), proper administration of nasal decongestants makes this agents act only on the mucosa, reducing and even eliminating the risk of hypertension and other systemic side effects like prostate enlargement, increased workload of the heart, and others.
Another concern for ?-adrenergic agonism would be tolerance and dependence. However, this adverse effect is associated with other agents such as ephedrine, pseudoephedrine, proplyhexedrine and phenylpropanolamine. As mentioned, this a problem for orally and intravenously administered agents. Some studies suggest that topical decongestants do not develop tolerance.
Rhinitis medicamentosa, also called as rebound rhinitis or chemical rhinitis, is a drug induced rhinitis in which the nasal mucosa is induced by excessive use of decongestants (Graf, 2005). With prolonged use of these drugs (not more than ten days), a rebound congestion occurs in which further uses of topical decongestants are not able to reverse. The pathophysiology of rhinitis medicamentosa is unknown (Ramey, et al., 2006).
Rhinitis medicamentosa is present in all of these agents.
Oral decongestants are contraindicated for pediatrics, geriatrics and pregnant women, due to their systemic absorption. Nasal decongestants, on the other hand, are logically safe due to the localized effects. However, Greenstein reported that naphazoline to have caused profound slumber. Other nasal decongestants which are supposedly safe have also been reported to have caused systemic adverse effects on pediatrics, and infants. Mahieu and colleagues have reported intoxication of a 15 month infant with naphazoline. They further recommend that these agents should be kept out of reach of children.
Among the different agents, xylometazoline is the only nasal decongestant approved for infant and pediatric use. The World Health Organization in fact have included xylometazoline in the essential medicine list, and is the only topical decongestant recommended for ear, nose and throat conditions specifically for children not less than 3 months of age.
In conclusion, nasal decongestants are solutions or suspensions used for the management of rhinitis and common colds. These agents are available as nasal sprays or drops. Belonging to the same drug class, they possess the same mechanism of action. Compared to oral decongestants, these agents have better safety profile; tolerance and dependence is not much of a concern, as well as aggravation of other medical conditions like heart problems and hypertension. However, their use is limited to not more than five days due to the development of rhinitis medicamentosa.
All agents are clinically effective, however, for a more lasting and better decongestion, the imidazolines, particularly xylometazoline is recommended; xylometazoline is also the only agent recommended for children. If nasal mucosal damage is of concern, phenylephrine is the agent of choice.
DeBernardis, J. F., Winn, M., Kerkman, D. J., et al., 1987, A new nasal decongestant, A-57219: a comparison with oxymetazoline.
Di Piro, J. T., Talbert, R. L., Yee, G. C., et al., 2008, Pharmacotherapy, A pathophysiologic approach, 7th ed. NY: The McGraw-Hill Co, 1565
Eskiizmir, G., Hircin, Z., Ozyurt, B., and Unlu, H., 2011, A comparative analysis of the decongestive effect of oxymetazoline and xylometazoline in healthy subjects.
Graf. P., 2005, Rhinitis medicamentosa: a review of causes and treatment, Treat Respir Med. 4:21-29
Greenstein, N. M., Reactions following use of nasal decongestants.
Hamels, K., and Clement, P. A. R., 1994, Decongestant capacity of two frequently used topical nasal decongestants in healthy persons, Acta Otolaryngol Belg. 48:265-269
Johnson, D. A., Hricik, J. G., 1993, The pharmacology of alpha-adrenergic decongestants.
Kobayashi, R. H., Kiechel, F. 3rd, Kobayashi, A. L., Mellion, M. B., 1994, Topical nasal sprays: treatment of allergic rhinitis.
Mahieu, L. M., Rooman, R. P., and Goossens, E., Imidazoline intoxication in children.
Merck and Co., Inc., 1982, The merck manual, 14th ed. NJ: Merck Sharp & Dohme Research Laboratories, 315
Pray, W. S., 2004, Safe use of nasal decongestants.
Ramey, J. T., Bailen, E., and Lockey, R. F., 2006, Rhinitis medicamentosa.
Sweetman, S. C. ed., 2009, Martindale, The complete drug reference 36th ed, London: Pharmaceutical Press, 1548
van Cauwenberge, P., Bachert, C., Passalacqua, G., et al., 2000, Consensus statement* on the treatment of allergic rhinitis
Takeno, S., Kawamoto, H., Hirata, S., et al., 1998, Decongesting effect of tramazoline on nasal airway patency and nasal symptoms as evaluated by acoustic rhinometry: an objective study in 30 allergic and six non-allergic subjects
World Health Organization, 2010, WHO Model list of essential medicine 16th list
Xylometazoline / Otrivin Review Article