Pharmacologic management of allergic rhinitis

Abstract

Allergic rhinitis is an immunoglobulin E (IgE)-mediated response to an allergen. The induction and elicitation of this response can be divided into three sequential stages: (1) sensitization and production of allergen-specific IgE; (2) reexposure to the allergen, causing cross-linkage of mast cell- and basophil-bound IgE and the release of mediators that produces the acute allergic reaction; and (3) elicitation of late inflammatory reactions via transendothelial migration and activation of eosinophils, neutrophils, and T cells in the nasal mucosa. This third stage results in chronic allergic inflammation.Exposure to an allergen initially excites the early allergic response, which is a result of release and generation of mast cell mediators. The response is marked by immediate sneezing, rhinorrhea, pruritus, and congestion. Thereafter, most persons experience cellular infiltration of the nasal mucosa, which causes the late-phase reaction. Late inflammation is associated with increased sensitivity to allergen after repeated exposures, and with hyperresponsiveness to irritants or certain pharmacologic agents. This is also known as priming. Accumulation of inflammatory cells (i.e., T cells, eosinophils, neutrophils, basophils) is characteristic of chronic allergic rhinitis and is responsible for nasal congestion, anosmia, and nasal hyperreactivity. Histamine, which is released following exposure to a specific allergen, is responsible for most of the symptoms of acute allergic rhinitis. These include sneezing, nasal congestion and/or rhinorrhea, and pruritus of the eyes and/or nose.Antihistamines as the Cornerstone of Pharmacologic Management in Allergic RhinitisAntihistamines have been used in the treatment of allergic rhinitis for more than 50 years. Their therapeutic effect is based on the blockade of H1 histamine receptors located on the nasal vasculature and nerve endings. Because antihistamines can effectively block receptor sites before histamine release, best results are obtained when they are administered on a regular basis and as a prophylactic measure to allergic persons prior to allergen exposure.1Hornby P Abrahams T Pulmonary pharmacology.Clin Obstet Gynecol. 1996; 39: 17-35Crossref PubMed Scopus (19) Google ScholarDifferences between first-generation (sedating) and second-generation (nonsedating) antihistaminesPharmacokinetics and pharmacodynamicsAll antihistamines are readily absorbed and reach peak concentrations 2 hours after oral administration.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google Scholar All the first-generation and most of the second-generation antihistamines are metabolized by the hepatic cytochrome P-450 system, with half-life values ranging from less than 24 hours for terfenadine, loratadine, and cetirizine and up to 9.5 days for astemizole and its active metabolites. These half-life values may be prolonged in elderly patients, patients with hepatic dysfunction, or patients concomitantly receiving other P-450 inhibitors, such as ketoconazole and erythromycin.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google ScholarThe peak effect of antihistamines generally occurs 5 to 7 hours after a single oral dose and between 3 and 5 hours after peak serum concentrations are reached; however, active metabolites and high tissue-to-serum concentration ratios of the drug prolong drug effectiveness even after serum concentrations of the parent drug have declined. Antihistamines should therefore be given before exposure to allergen to achieve maximum efficacy.3Clissold SP Sorkin EM Goa LK Loratadine: a preliminary review of its pharmacodynamic properties and therapeutic efficacy.Drugs. 1989; 37: 42-57Crossref PubMed Scopus (126) Google ScholarSide effectsTable 1Side effects of first-generation antihistaminesSedationImpairment of ability to perform tasksGastrointestinal complaintsAnticholinergic effectsDry mouthImpotenceDifficult urinationSerious cardiovascular effects with high blood levels Open table in a new tab In contrast, the piperazine- or piperidine-like structure of the second-generation antihistamines makes it difficult for them to penetrate the CNS. They also do not bind to muscarinic cholinergic receptors, β-adrenergic receptors, dopamine receptors, or serotonin receptors. As a result, most second-generation antihistamines do not cause drowsiness, fatigue, or any anticholinergic effects, and do not enhance the adverse CNS effects of drugs such as alcohol and diazepam.Table 2Second-generation antihistamines and antihistamine/decongestant combinationsOnsetSedationCardiac side effectsPregnancy categoryDosing/complianceAstemizole1–2 hrNoYesCq.d.Cetirizine1–2 hrYesNoBq.d.Fexofenadine1–2 hrNoNoCb.i.d.Loratadine1–2 hrNoNoBq.d.Loratadine/pseudoephedrine1–2 hrNoNo†Bq.d.b.i.d.Terfenadine/*Pseudoephedrine1–2 hrNoYesCb.i.d.*Pending U.S. Food and Drug Administration withdrawal at time of printing.†Except for an occasional increase in heart rate and/or blood pressure. Open table in a new tab Intranasal Corticosteroids as Effective Controllers of the Inflammatory Process in Allergic RhinitisTable 3Intranasal corticosteroids: current formulationsDrugTrade name (dose/spray)Daily dose/nostrilPediatric indicationTriamcinolone*Nasacort® (55 μg)2 Sprays, q.d. 1 Spray, b.i.d.≥12 yrBeclomethasone*Vancenase®† (42 or 84 μg)2 Sprays, b.i.d. (for 42 μg) 2 Sprays, q.d.,or 1 spray, b.i.d. (for 84 μg)≥6 yrBeconase® (42 μg)2 Sprays, b.i.d.Flunisolide‡Nasarel® (25 μg)2–4 Sprays, b.i.d.≥6 yrBudesonide§Rhinocort® (32 μg)4 Sprays, q.d. 1–2 Sprays, b.i.d.≥6 yrFluticasone‡Flonase™ (50 μg)2 Sprays, q.d. 1 Spray, b.i.d.≥12 yr*Freon aerosol and aqueous pump spray.†Available in double-strength dose, 84 μg/spray.‡Aqueous pump spray.§Aerosol spray. Open table in a new tab Mechanism of actionIntranasal corticosteroids modify the inflammatory process by modifying gene expression. When glucocorticoids combine with intracellular steroid receptors, the resulting complex interacts with DNA to form cell-regulating proteins. These proteins inhibit leukocyte priming, limit the secretion of cytokines and other mediators, and modulate enzyme systems. They also inhibit the migration of mast cells into the nasal mucosa, and induce eosinopenia. These regulatory proteins also decrease microvascular permeability and edema, and inhibit mucus secretion.Clinical benefit of intranasal corticosteroidsTabled 1Prolonged local actionRare systemic effectsRapid systemic metabolismPotentFew local side effectsEfficacious for allergic and nonallergic rhinitis Open table in a new tab Oral and Topical DecongestantsDecongestants improve nasal patency through their suppressive action on the volume of blood in the sinuses and on the volume of blood supplied to the mucosa; the amount of mucosal edema and the amount of liquid on the mucosal surface are decreased. This action is achieved through either oral or topical administration of decongestants.Mechanism of actionDecongestants are α-adrenergic agonists. As such, they affect α-adrenergic receptors located on postsynaptic membranes (e.g., on vascular smooth muscle). The response to receptor activation by decongestants results in regulation of norepinephrine release and decreased sympathetic output.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google ScholarTemporary relief of congestion can be achieved with a variety of sympathomimetic drugs in the form of nose drops and nasal sprays. Although the short-acting agent phenylephrine hydrochloride, and the longer-acting agents oxymetazoline hydrochloride and xylometazoline hydrochloride, do not have systemic effects, their continued use for more than 5 or 7 days can lead to a progressively more severe nasal obstruction known as rhinitis medicamentosa.8Salvaggio J Allergic rhinitis.in: Cecil textbook of medicine. WB Saunders, Philadelphia1992: 1457-1462Google Scholar When this occurs, the patient must abruptly discontinue use of the drug(s) to alleviate the condition. A course of intranasal corticosteroids for a few weeks may also be needed to decrease the nasal congestion of this condition. Topical vasoconstrictors should not be used in children under 1 year of age.6Eur J Allergy Clin Immunol. 1994; 49: 1-36Crossref Scopus (82) Google ScholarNewer oral formulations containing an antihistamine and a decongestant and which improve both the signs and symptoms of allergic rhinitis have recently been introduced. This dosage form is more convenient to use than administering separate doses of each drug, and should increase compliance in those patients who require an antihistamine and a decongestant.9Clinical Study Report (CSR).Safety and efficacy of Claritin-D lessens the severity of asthma associated with seasonal allergic rhinitis. Schering-Plough Corporation, Kenilworth, NJNovember 1995Google ScholarCromolyn SodiumCromolyn sodium is a topically administered antiallergenic agent used to reduce nasal itching, sneezing, hypersecretion, and nasal blockage in allergic rhinitis. It gives dose-related protection against both the immediate and the late response of an allergic reaction, and is generally well tolerated by patients, with only mild nasal irritation or burning reported. The major disadvantage to using cromolyn sodium is its frequent dosing requirement (one to two sprays in each nostril every 4 hours), which reduces compliance. It is also ineffective in 30% to 40% of the population despite strict adherence to this frequent-dosing regimen.4Creticos P Allergic rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1394-1414Google ScholarMechanism of actionCromolyn sodium inhibits IgE-dependent allergic reactions by reducing the release of histamine and other mediators from mast cells. The drug accomplishes this through binding to receptor-like proteins in the cell membrane.ConclusionThe goal in managing allergic rhinitis pharmacologically is to begin treatment prophylactically so that symptoms never appear or, if debilitating symptoms are apparent or persistent, to control them without causing any alteration in the patient's functional capacity. Nonsedating antihistamines, alone or in combination with decongestants, and intranasal corticosteroids are safe and effective medications for treating the symptoms of allergic rhinitis. Allergic rhinitis is an immunoglobulin E (IgE)-mediated response to an allergen. The induction and elicitation of this response can be divided into three sequential stages: (1) sensitization and production of allergen-specific IgE; (2) reexposure to the allergen, causing cross-linkage of mast cell- and basophil-bound IgE and the release of mediators that produces the acute allergic reaction; and (3) elicitation of late inflammatory reactions via transendothelial migration and activation of eosinophils, neutrophils, and T cells in the nasal mucosa. This third stage results in chronic allergic inflammation. Exposure to an allergen initially excites the early allergic response, which is a result of release and generation of mast cell mediators. The response is marked by immediate sneezing, rhinorrhea, pruritus, and congestion. Thereafter, most persons experience cellular infiltration of the nasal mucosa, which causes the late-phase reaction. Late inflammation is associated with increased sensitivity to allergen after repeated exposures, and with hyperresponsiveness to irritants or certain pharmacologic agents. This is also known as priming. Accumulation of inflammatory cells (i.e., T cells, eosinophils, neutrophils, basophils) is characteristic of chronic allergic rhinitis and is responsible for nasal congestion, anosmia, and nasal hyperreactivity. Histamine, which is released following exposure to a specific allergen, is responsible for most of the symptoms of acute allergic rhinitis. These include sneezing, nasal congestion and/or rhinorrhea, and pruritus of the eyes and/or nose. Antihistamines as the Cornerstone of Pharmacologic Management in Allergic RhinitisAntihistamines have been used in the treatment of allergic rhinitis for more than 50 years. Their therapeutic effect is based on the blockade of H1 histamine receptors located on the nasal vasculature and nerve endings. Because antihistamines can effectively block receptor sites before histamine release, best results are obtained when they are administered on a regular basis and as a prophylactic measure to allergic persons prior to allergen exposure.1Hornby P Abrahams T Pulmonary pharmacology.Clin Obstet Gynecol. 1996; 39: 17-35Crossref PubMed Scopus (19) Google ScholarDifferences between first-generation (sedating) and second-generation (nonsedating) antihistaminesPharmacokinetics and pharmacodynamicsAll antihistamines are readily absorbed and reach peak concentrations 2 hours after oral administration.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google Scholar All the first-generation and most of the second-generation antihistamines are metabolized by the hepatic cytochrome P-450 system, with half-life values ranging from less than 24 hours for terfenadine, loratadine, and cetirizine and up to 9.5 days for astemizole and its active metabolites. These half-life values may be prolonged in elderly patients, patients with hepatic dysfunction, or patients concomitantly receiving other P-450 inhibitors, such as ketoconazole and erythromycin.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google ScholarThe peak effect of antihistamines generally occurs 5 to 7 hours after a single oral dose and between 3 and 5 hours after peak serum concentrations are reached; however, active metabolites and high tissue-to-serum concentration ratios of the drug prolong drug effectiveness even after serum concentrations of the parent drug have declined. Antihistamines should therefore be given before exposure to allergen to achieve maximum efficacy.3Clissold SP Sorkin EM Goa LK Loratadine: a preliminary review of its pharmacodynamic properties and therapeutic efficacy.Drugs. 1989; 37: 42-57Crossref PubMed Scopus (126) Google ScholarSide effectsTable 1Side effects of first-generation antihistaminesSedationImpairment of ability to perform tasksGastrointestinal complaintsAnticholinergic effectsDry mouthImpotenceDifficult urinationSerious cardiovascular effects with high blood levels Open table in a new tab In contrast, the piperazine- or piperidine-like structure of the second-generation antihistamines makes it difficult for them to penetrate the CNS. They also do not bind to muscarinic cholinergic receptors, β-adrenergic receptors, dopamine receptors, or serotonin receptors. As a result, most second-generation antihistamines do not cause drowsiness, fatigue, or any anticholinergic effects, and do not enhance the adverse CNS effects of drugs such as alcohol and diazepam.Table 2Second-generation antihistamines and antihistamine/decongestant combinationsOnsetSedationCardiac side effectsPregnancy categoryDosing/complianceAstemizole1–2 hrNoYesCq.d.Cetirizine1–2 hrYesNoBq.d.Fexofenadine1–2 hrNoNoCb.i.d.Loratadine1–2 hrNoNoBq.d.Loratadine/pseudoephedrine1–2 hrNoNo†Bq.d.b.i.d.Terfenadine/*Pseudoephedrine1–2 hrNoYesCb.i.d.*Pending U.S. Food and Drug Administration withdrawal at time of printing.†Except for an occasional increase in heart rate and/or blood pressure. Open table in a new tab Antihistamines have been used in the treatment of allergic rhinitis for more than 50 years. Their therapeutic effect is based on the blockade of H1 histamine receptors located on the nasal vasculature and nerve endings. Because antihistamines can effectively block receptor sites before histamine release, best results are obtained when they are administered on a regular basis and as a prophylactic measure to allergic persons prior to allergen exposure.1Hornby P Abrahams T Pulmonary pharmacology.Clin Obstet Gynecol. 1996; 39: 17-35Crossref PubMed Scopus (19) Google Scholar Differences between first-generation (sedating) and second-generation (nonsedating) antihistaminesPharmacokinetics and pharmacodynamicsAll antihistamines are readily absorbed and reach peak concentrations 2 hours after oral administration.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google Scholar All the first-generation and most of the second-generation antihistamines are metabolized by the hepatic cytochrome P-450 system, with half-life values ranging from less than 24 hours for terfenadine, loratadine, and cetirizine and up to 9.5 days for astemizole and its active metabolites. These half-life values may be prolonged in elderly patients, patients with hepatic dysfunction, or patients concomitantly receiving other P-450 inhibitors, such as ketoconazole and erythromycin.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google ScholarThe peak effect of antihistamines generally occurs 5 to 7 hours after a single oral dose and between 3 and 5 hours after peak serum concentrations are reached; however, active metabolites and high tissue-to-serum concentration ratios of the drug prolong drug effectiveness even after serum concentrations of the parent drug have declined. Antihistamines should therefore be given before exposure to allergen to achieve maximum efficacy.3Clissold SP Sorkin EM Goa LK Loratadine: a preliminary review of its pharmacodynamic properties and therapeutic efficacy.Drugs. 1989; 37: 42-57Crossref PubMed Scopus (126) Google ScholarSide effectsTable 1Side effects of first-generation antihistaminesSedationImpairment of ability to perform tasksGastrointestinal complaintsAnticholinergic effectsDry mouthImpotenceDifficult urinationSerious cardiovascular effects with high blood levels Open table in a new tab In contrast, the piperazine- or piperidine-like structure of the second-generation antihistamines makes it difficult for them to penetrate the CNS. They also do not bind to muscarinic cholinergic receptors, β-adrenergic receptors, dopamine receptors, or serotonin receptors. As a result, most second-generation antihistamines do not cause drowsiness, fatigue, or any anticholinergic effects, and do not enhance the adverse CNS effects of drugs such as alcohol and diazepam.Table 2Second-generation antihistamines and antihistamine/decongestant combinationsOnsetSedationCardiac side effectsPregnancy categoryDosing/complianceAstemizole1–2 hrNoYesCq.d.Cetirizine1–2 hrYesNoBq.d.Fexofenadine1–2 hrNoNoCb.i.d.Loratadine1–2 hrNoNoBq.d.Loratadine/pseudoephedrine1–2 hrNoNo†Bq.d.b.i.d.Terfenadine/*Pseudoephedrine1–2 hrNoYesCb.i.d.*Pending U.S. Food and Drug Administration withdrawal at time of printing.†Except for an occasional increase in heart rate and/or blood pressure. Open table in a new tab Pharmacokinetics and pharmacodynamicsAll antihistamines are readily absorbed and reach peak concentrations 2 hours after oral administration.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google Scholar All the first-generation and most of the second-generation antihistamines are metabolized by the hepatic cytochrome P-450 system, with half-life values ranging from less than 24 hours for terfenadine, loratadine, and cetirizine and up to 9.5 days for astemizole and its active metabolites. These half-life values may be prolonged in elderly patients, patients with hepatic dysfunction, or patients concomitantly receiving other P-450 inhibitors, such as ketoconazole and erythromycin.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google ScholarThe peak effect of antihistamines generally occurs 5 to 7 hours after a single oral dose and between 3 and 5 hours after peak serum concentrations are reached; however, active metabolites and high tissue-to-serum concentration ratios of the drug prolong drug effectiveness even after serum concentrations of the parent drug have declined. Antihistamines should therefore be given before exposure to allergen to achieve maximum efficacy.3Clissold SP Sorkin EM Goa LK Loratadine: a preliminary review of its pharmacodynamic properties and therapeutic efficacy.Drugs. 1989; 37: 42-57Crossref PubMed Scopus (126) Google Scholar All antihistamines are readily absorbed and reach peak concentrations 2 hours after oral administration.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google Scholar All the first-generation and most of the second-generation antihistamines are metabolized by the hepatic cytochrome P-450 system, with half-life values ranging from less than 24 hours for terfenadine, loratadine, and cetirizine and up to 9.5 days for astemizole and its active metabolites. These half-life values may be prolonged in elderly patients, patients with hepatic dysfunction, or patients concomitantly receiving other P-450 inhibitors, such as ketoconazole and erythromycin.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google Scholar The peak effect of antihistamines generally occurs 5 to 7 hours after a single oral dose and between 3 and 5 hours after peak serum concentrations are reached; however, active metabolites and high tissue-to-serum concentration ratios of the drug prolong drug effectiveness even after serum concentrations of the parent drug have declined. Antihistamines should therefore be given before exposure to allergen to achieve maximum efficacy.3Clissold SP Sorkin EM Goa LK Loratadine: a preliminary review of its pharmacodynamic properties and therapeutic efficacy.Drugs. 1989; 37: 42-57Crossref PubMed Scopus (126) Google Scholar Side effectsTable 1Side effects of first-generation antihistaminesSedationImpairment of ability to perform tasksGastrointestinal complaintsAnticholinergic effectsDry mouthImpotenceDifficult urinationSerious cardiovascular effects with high blood levels Open table in a new tab In contrast, the piperazine- or piperidine-like structure of the second-generation antihistamines makes it difficult for them to penetrate the CNS. They also do not bind to muscarinic cholinergic receptors, β-adrenergic receptors, dopamine receptors, or serotonin receptors. As a result, most second-generation antihistamines do not cause drowsiness, fatigue, or any anticholinergic effects, and do not enhance the adverse CNS effects of drugs such as alcohol and diazepam.Table 2Second-generation antihistamines and antihistamine/decongestant combinationsOnsetSedationCardiac side effectsPregnancy categoryDosing/complianceAstemizole1–2 hrNoYesCq.d.Cetirizine1–2 hrYesNoBq.d.Fexofenadine1–2 hrNoNoCb.i.d.Loratadine1–2 hrNoNoBq.d.Loratadine/pseudoephedrine1–2 hrNoNo†Bq.d.b.i.d.Terfenadine/*Pseudoephedrine1–2 hrNoYesCb.i.d.*Pending U.S. Food and Drug Administration withdrawal at time of printing.†Except for an occasional increase in heart rate and/or blood pressure. Open table in a new tab In contrast, the piperazine- or piperidine-like structure of the second-generation antihistamines makes it difficult for them to penetrate the CNS. They also do not bind to muscarinic cholinergic receptors, β-adrenergic receptors, dopamine receptors, or serotonin receptors. As a result, most second-generation antihistamines do not cause drowsiness, fatigue, or any anticholinergic effects, and do not enhance the adverse CNS effects of drugs such as alcohol and diazepam. *Pending U.S. Food and Drug Administration withdrawal at time of printing. †Except for an occasional increase in heart rate and/or blood pressure. Intranasal Corticosteroids as Effective Controllers of the Inflammatory Process in Allergic RhinitisTable 3Intranasal corticosteroids: current formulationsDrugTrade name (dose/spray)Daily dose/nostrilPediatric indicationTriamcinolone*Nasacort® (55 μg)2 Sprays, q.d. 1 Spray, b.i.d.≥12 yrBeclomethasone*Vancenase®† (42 or 84 μg)2 Sprays, b.i.d. (for 42 μg) 2 Sprays, q.d.,or 1 spray, b.i.d. (for 84 μg)≥6 yrBeconase® (42 μg)2 Sprays, b.i.d.Flunisolide‡Nasarel® (25 μg)2–4 Sprays, b.i.d.≥6 yrBudesonide§Rhinocort® (32 μg)4 Sprays, q.d. 1–2 Sprays, b.i.d.≥6 yrFluticasone‡Flonase™ (50 μg)2 Sprays, q.d. 1 Spray, b.i.d.≥12 yr*Freon aerosol and aqueous pump spray.†Available in double-strength dose, 84 μg/spray.‡Aqueous pump spray.§Aerosol spray. Open table in a new tab Mechanism of actionIntranasal corticosteroids modify the inflammatory process by modifying gene expression. When glucocorticoids combine with intracellular steroid receptors, the resulting complex interacts with DNA to form cell-regulating proteins. These proteins inhibit leukocyte priming, limit the secretion of cytokines and other mediators, and modulate enzyme systems. They also inhibit the migration of mast cells into the nasal mucosa, and induce eosinopenia. These regulatory proteins also decrease microvascular permeability and edema, and inhibit mucus secretion.Clinical benefit of intranasal corticosteroidsTabled 1Prolonged local actionRare systemic effectsRapid systemic metabolismPotentFew local side effectsEfficacious for allergic and nonallergic rhinitis Open table in a new tab *Freon aerosol and aqueous pump spray. †Available in double-strength dose, 84 μg/spray. ‡Aqueous pump spray. §Aerosol spray. Mechanism of actionIntranasal corticosteroids modify the inflammatory process by modifying gene expression. When glucocorticoids combine with intracellular steroid receptors, the resulting complex interacts with DNA to form cell-regulating proteins. These proteins inhibit leukocyte priming, limit the secretion of cytokines and other mediators, and modulate enzyme systems. They also inhibit the migration of mast cells into the nasal mucosa, and induce eosinopenia. These regulatory proteins also decrease microvascular permeability and edema, and inhibit mucus secretion. Intranasal corticosteroids modify the inflammatory process by modifying gene expression. When glucocorticoids combine with intracellular steroid receptors, the resulting complex interacts with DNA to form cell-regulating proteins. These proteins inhibit leukocyte priming, limit the secretion of cytokines and other mediators, and modulate enzyme systems. They also inhibit the migration of mast cells into the nasal mucosa, and induce eosinopenia. These regulatory proteins also decrease microvascular permeability and edema, and inhibit mucus secretion. Clinical benefit of intranasal corticosteroidsTabled 1Prolonged local actionRare systemic effectsRapid systemic metabolismPotentFew local side effectsEfficacious for allergic and nonallergic rhinitis Open table in a new tab Oral and Topical DecongestantsDecongestants improve nasal patency through their suppressive action on the volume of blood in the sinuses and on the volume of blood supplied to the mucosa; the amount of mucosal edema and the amount of liquid on the mucosal surface are decreased. This action is achieved through either oral or topical administration of decongestants.Mechanism of actionDecongestants are α-adrenergic agonists. As such, they affect α-adrenergic receptors located on postsynaptic membranes (e.g., on vascular smooth muscle). The response to receptor activation by decongestants results in regulation of norepinephrine release and decreased sympathetic output.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google ScholarTemporary relief of congestion can be achieved with a variety of sympathomimetic drugs in the form of nose drops and nasal sprays. Although the short-acting agent phenylephrine hydrochloride, and the longer-acting agents oxymetazoline hydrochloride and xylometazoline hydrochloride, do not have systemic effects, their continued use for more than 5 or 7 days can lead to a progressively more severe nasal obstruction known as rhinitis medicamentosa.8Salvaggio J Allergic rhinitis.in: Cecil textbook of medicine. WB Saunders, Philadelphia1992: 1457-1462Google Scholar When this occurs, the patient must abruptly discontinue use of the drug(s) to alleviate the condition. A course of intranasal corticosteroids for a few weeks may also be needed to decrease the nasal congestion of this condition. Topical vasoconstrictors should not be used in children under 1 year of age.6Eur J Allergy Clin Immunol. 1994; 49: 1-36Crossref Scopus (82) Google ScholarNewer oral formulations containing an antihistamine and a decongestant and which improve both the signs and symptoms of allergic rhinitis have recently been introduced. This dosage form is more convenient to use than administering separate doses of each drug, and should increase compliance in those patients who require an antihistamine and a decongestant.9Clinical Study Report (CSR).Safety and efficacy of Claritin-D lessens the severity of asthma associated with seasonal allergic rhinitis. Schering-Plough Corporation, Kenilworth, NJNovember 1995Google Scholar Decongestants improve nasal patency through their suppressive action on the volume of blood in the sinuses and on the volume of blood supplied to the mucosa; the amount of mucosal edema and the amount of liquid on the mucosal surface are decreased. This action is achieved through either oral or topical administration of decongestants. Mechanism of actionDecongestants are α-adrenergic agonists. As such, they affect α-adrenergic receptors located on postsynaptic membranes (e.g., on vascular smooth muscle). The response to receptor activation by decongestants results in regulation of norepinephrine release and decreased sympathetic output.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google ScholarTemporary relief of congestion can be achieved with a variety of sympathomimetic drugs in the form of nose drops and nasal sprays. Although the short-acting agent phenylephrine hydrochloride, and the longer-acting agents oxymetazoline hydrochloride and xylometazoline hydrochloride, do not have systemic effects, their continued use for more than 5 or 7 days can lead to a progressively more severe nasal obstruction known as rhinitis medicamentosa.8Salvaggio J Allergic rhinitis.in: Cecil textbook of medicine. WB Saunders, Philadelphia1992: 1457-1462Google Scholar When this occurs, the patient must abruptly discontinue use of the drug(s) to alleviate the condition. A course of intranasal corticosteroids for a few weeks may also be needed to decrease the nasal congestion of this condition. Topical vasoconstrictors should not be used in children under 1 year of age.6Eur J Allergy Clin Immunol. 1994; 49: 1-36Crossref Scopus (82) Google ScholarNewer oral formulations containing an antihistamine and a decongestant and which improve both the signs and symptoms of allergic rhinitis have recently been introduced. This dosage form is more convenient to use than administering separate doses of each drug, and should increase compliance in those patients who require an antihistamine and a decongestant.9Clinical Study Report (CSR).Safety and efficacy of Claritin-D lessens the severity of asthma associated with seasonal allergic rhinitis. Schering-Plough Corporation, Kenilworth, NJNovember 1995Google Scholar Decongestants are α-adrenergic agonists. As such, they affect α-adrenergic receptors located on postsynaptic membranes (e.g., on vascular smooth muscle). The response to receptor activation by decongestants results in regulation of norepinephrine release and decreased sympathetic output.2Simons E New medications for rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1325-1336Google Scholar Temporary relief of congestion can be achieved with a variety of sympathomimetic drugs in the form of nose drops and nasal sprays. Although the short-acting agent phenylephrine hydrochloride, and the longer-acting agents oxymetazoline hydrochloride and xylometazoline hydrochloride, do not have systemic effects, their continued use for more than 5 or 7 days can lead to a progressively more severe nasal obstruction known as rhinitis medicamentosa.8Salvaggio J Allergic rhinitis.in: Cecil textbook of medicine. WB Saunders, Philadelphia1992: 1457-1462Google Scholar When this occurs, the patient must abruptly discontinue use of the drug(s) to alleviate the condition. A course of intranasal corticosteroids for a few weeks may also be needed to decrease the nasal congestion of this condition. Topical vasoconstrictors should not be used in children under 1 year of age.6Eur J Allergy Clin Immunol. 1994; 49: 1-36Crossref Scopus (82) Google Scholar Newer oral formulations containing an antihistamine and a decongestant and which improve both the signs and symptoms of allergic rhinitis have recently been introduced. This dosage form is more convenient to use than administering separate doses of each drug, and should increase compliance in those patients who require an antihistamine and a decongestant.9Clinical Study Report (CSR).Safety and efficacy of Claritin-D lessens the severity of asthma associated with seasonal allergic rhinitis. Schering-Plough Corporation, Kenilworth, NJNovember 1995Google Scholar Cromolyn SodiumCromolyn sodium is a topically administered antiallergenic agent used to reduce nasal itching, sneezing, hypersecretion, and nasal blockage in allergic rhinitis. It gives dose-related protection against both the immediate and the late response of an allergic reaction, and is generally well tolerated by patients, with only mild nasal irritation or burning reported. The major disadvantage to using cromolyn sodium is its frequent dosing requirement (one to two sprays in each nostril every 4 hours), which reduces compliance. It is also ineffective in 30% to 40% of the population despite strict adherence to this frequent-dosing regimen.4Creticos P Allergic rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1394-1414Google ScholarMechanism of actionCromolyn sodium inhibits IgE-dependent allergic reactions by reducing the release of histamine and other mediators from mast cells. The drug accomplishes this through binding to receptor-like proteins in the cell membrane. Cromolyn sodium is a topically administered antiallergenic agent used to reduce nasal itching, sneezing, hypersecretion, and nasal blockage in allergic rhinitis. It gives dose-related protection against both the immediate and the late response of an allergic reaction, and is generally well tolerated by patients, with only mild nasal irritation or burning reported. The major disadvantage to using cromolyn sodium is its frequent dosing requirement (one to two sprays in each nostril every 4 hours), which reduces compliance. It is also ineffective in 30% to 40% of the population despite strict adherence to this frequent-dosing regimen.4Creticos P Allergic rhinitis.in: Asthma and rhinitis. Blackwell Scientific Publications, Cambridge, MA1995: 1394-1414Google Scholar Mechanism of actionCromolyn sodium inhibits IgE-dependent allergic reactions by reducing the release of histamine and other mediators from mast cells. The drug accomplishes this through binding to receptor-like proteins in the cell membrane. Cromolyn sodium inhibits IgE-dependent allergic reactions by reducing the release of histamine and other mediators from mast cells. The drug accomplishes this through binding to receptor-like proteins in the cell membrane. ConclusionThe goal in managing allergic rhinitis pharmacologically is to begin treatment prophylactically so that symptoms never appear or, if debilitating symptoms are apparent or persistent, to control them without causing any alteration in the patient's functional capacity. Nonsedating antihistamines, alone or in combination with decongestants, and intranasal corticosteroids are safe and effective medications for treating the symptoms of allergic rhinitis. The goal in managing allergic rhinitis pharmacologically is to begin treatment prophylactically so that symptoms never appear or, if debilitating symptoms are apparent or persistent, to control them without causing any alteration in the patient's functional capacity. Nonsedating antihistamines, alone or in combination with decongestants, and intranasal corticosteroids are safe and effective medications for treating the symptoms of allergic rhinitis.