Allergic Rhinitis Pharmacotherapy

• Allergic rhinitis' treatment includes avoidance, pharmacotherapy, and immunotherapy.

Pharmacotherapy

• Includes antihistamines (diphenhydramine, hydroxicine, cetirizine, loratadine, desloratidine, fexofenadine, azelastine).
• Also includes intranasal glucocorticoids (fluticasone, mometasone).
• Systemic steroids are not a preferred option.
• Leukotriene modifiers like montelukast are an option
• Mast cell stabilizers such as cromolyn sodium are a treatment options
• Anticholinergics like ipratropium can be used
• Decongestants (phenylephrine, pseudoephedrine) are used in treatment

Antihistamines

• They block the effects of histamine.
• H1 receptor blockage leads to decreased itching and vascular permeability.
• Decreased mucosal secretions and cough receptor stimulation is achieved through H1 receptor blockage
• Bronchial smooth muscle relaxation occurs as a result of H1 receptor blockage

Additional Actions of Antihistamines

• 1st generation antihistamines (diphenhydramine, dimenhydrinate, hydroxyzine) may have non-histamine blockage actions like sedation, atropinic, and anti-emetic effects.
• 2nd generation antihistamines (cetirizine, loratadine, desloratidine, fexofenadine, azelastine) prevent mast cell release of mediators of inflammation.

Allergic Rhinitis - Anti-histamines Indications

• Drug of choice for mild to moderate rhinitis
• Best for exudative allergies (hay fever)
• Relieves sneezing, itching, nasal discharge, and ocular symptoms (itching, watery eyes, redness)
• May be given with a decongestant (pseudoephedrine).
• Both 1st and 2nd generation antihistamines are effective for seasonal rhinitis.
• 2nd generation drugs lack sedation.
• Intranasal glucocorticoids are used for severe allergic rhinitis (e.g., fluticasone).

Allergic Rhinitis - Anti-histamines Pharmacokinetics

• Administration routes depend on the antihistamine and symptoms: oral, intranasal, intraocular, or intravenous (only in anaphylaxis).
• Half-lives are variable, ranging 8-24 hours.
• Concentration in breast milk parallels plasma concentration.
• Effectiveness is best when administered before an anticipated allergic reaction.
• Most are metabolized by the cytochrome P450 system (CYP3A4).
• Grapefruit juice may block metabolism.

Allergic Rhinitis - Anti-histamines Adverse Effects

• 1st generation antihistamines (diphenhydramine, hydroxyzine) are blood-brain-barrier permeable, causing CNS effects like atropinic effects, somnolence, and cognitive/psychomotor problems.
• There's a limited use of first-generation antihistamines for children under 6 years, and they forbidden for children under 2 years in Canada.
• First-generation antihistamines are not recommended during pregnancy or nursing.
• 2nd generation antihistamines (cetirizine, loratadine, fexofenadine) are well tolerated.
• Poor blood-brain-barrier penetration in 2nd generation antihistamines results in no CNS effects; sedation is not a major issue.
• Cetirizine has long term safety in children.
• Intranasal administration leads to rapid onset (e.g., azelastine).

Intranasal Glucocorticoids

• Fluticasone and Mometasone are effective for nasal and ocular symptoms (itching, sneezing, discharge, congestion).
• They're most effective for prevention and treatment.
• Glucocorticoids are the preferred choice for moderate to severe allergic rhinitis.
• The optimal dose is at the plateau of the dose-response curve; increasing the dose raises side effects without additional benefits.
• Effective when taken once daily, but it may take 7 days to be maximally effective.
• Side effects include epistaxis.
• They have mild side effects compared to oral glucocorticoids.

Oral Glucocorticoids

• Oral administration is a last resort because systemic delivery can cause major side effects on growth, bone density, cataract formation, and intraocular pressure.
• Intranasal administration is the best choice

Leukotriene Receptor Antagonist

• Leukotrienes are released during allergic inflammation by mast cells, eosinophils, basophils, and inflammatory cells.
• Leukotrienes are involved in infiltration of inflammatory cells, mucus secretion, and airway (bronchiolar) constriction.
• Montelukast acts as a leukotriene receptor antagonist.
• It gives modest relief of congestion, itching, and discharge,.
• It is less effective than intranasal glucocorticoids.
• It is normally used with an antihistamine or intranasal glucocorticoid.

Mast-cell Stabilizer

• Mast cells are activated in response to allergens.
• Activated mast cells release inflammatory mediators (histamine, leukotrienes, PG, PAF, etc).
• Cromolyn sodium inhibits mast cell degranulation and release of mediators.
• Less effective than intranasal corticoid steroids.
• Must be given BEFORE exposure.
• Almost no local or systemic toxicity.

Anticholinergic

• Ipratropium is an antimuscarinic.
• Reduces mucus secretion but has no effect on inflammation; does not relieve sneezing, itching, or congestion.
• Useful if the primary symptom is nasal discharge.
• Adverse effects are atropinic (dry mucous membranes, urinary retention).
• Caution is needed in glaucoma and prostatic hypertrophy.
• Intranasal administration limits systemic adverse effects and the atropinic effects are beneficial in nostrils.

Decongestant

• Pseudoephedrine acts as an α1-adrenergic receptor agonist, causing increased vasoconstriction and reduced nasal swelling.
• It also has a non-adrenergic effect, leading to increased mucociliary clearance and more liquid mucus.
• Provides relief of congestion only, but not helpful for sneezing, itching, or discharge.
• Phenylephrine acts as an α1-adrenergic receptor agonist.
• Replaces pseudoephedrine, as pseudoephedrine use is reduced from the market due to street use for illicit purposes.
• The efficacy of phenylephrine is less than pseudoephedrine.

Decongestant Adverse Effects

• Many adverse effects include insomnia, nervousness, headache, palpitations, hypertension, and urinary retention.
• Topical intranasal application has fewer systemic effects.
• Contraindicated for people taking MAO inhibitors, caution for those with heart disease, high blood pressure, diabetes, glaucoma, thyroid disorder, or enlarged prostate.
• Intranasal decongestants should not be used longer than 3 days, as there is potential for rebound congestion.
• Oral decongestants should not be used longer than 7 days.
• Often given with antihistamines.

Response to Medications

• Oral/intranasal antihistamines are rated +++ for sneezing and itching, +/- for congestion, ++ for rhinorrhea and ++/+/- for eye symptoms
• Intranasal glucocorticoids are rated +++ for sneezing, ++ for itching, +++ for congestion, +++ for rhinorrhea and +/- for eye symptoms
• Leukotriene modifiers are rated ++ for sneezing, itching, congestion, rhinorrhea and eye symptoms
• Intranasal anticholinergics are rated + for sneezing, itching, and congestion, and ++ for rhinorrhea and eye symptoms
• Intranasal mast cell stabilizers are rated + for sneezing, itching, and congestion, and + for rhinorrhea and - for eye symptoms
• Oral/intranasal decongestants are rated - for sneezing and itching, ++ for congestion, and - for rhinorrhea and eye symptoms

Allergen Specific Immunotherapy

• Can be administered as subcutaneous (sc) allergen immunotherapy or sublingually.
• It involves administering increasing doses of a solution of allergens to which the patient is sensitive (determined through skin tests).
• The buildup period involves weekly, then monthly injections for about 3-6 months.
• The dose is increased so symptoms remain within injection area, but symptom are reduced with natural exposure.
• Once the desired dose is established, monthly maintenance begins.
• The maintenance period involves monthly injections with desired dose for 3-5 years.
• This reduces symptoms with natural exposure however, the benefits may continue when therapy is discontinued.
• Indications include IgE in serum or skin sensitivity to an allergen, poor pharmacotherapy response, or patient preference.
• Avoid in severe asthma, cardiovascular disease, and high dose β-adrenergic receptor blocker; do not initiate during pregnancy.
• Requires multiple visits, so patient compliance is important.
• Poor compliance is associated with systemic reactions.
• May be as effective as intranasal glucocorticoids.
• It may add endogenous glucocorticoid production and reduces allergen-specific IgE production.