Pharmacotherapy for Allergic Rhinitis
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1 Pharmacotherapy for Allergic Rhinitis William Reisacher, MD FACS FAAOA Assistant Professor Weill Cornell Medical College The Impact of Allergic Rhinitis Allergic rhinitis affects approximately 50 million people in the U.S., and the prevalence is rising. Allergies represent the 2 nd leading cause of chronic disease in the U.S., costing the healthcare system $18 billion annually. 3.4 million days lost from work annually and 2 million days lost from school. Approximately 25 % decline in worker productivity. The head and neck region is the shock organ for inhalant sensitivities. Symptoms of Allergic Rhinitis Sneezing 84% Anterior rhinorrhea 76% Itchy eyes 71% Nasal congestion 70% Itchy nose 56% Sinus pressure 52% Headache 49% Watery eyes 49% Classic Triad of Management IT Meds Avoidance What is the Best Medication? What is the Best Medication For You? 1
2 What is the Best Medication For You Now? Pharmacotherapy Target Therapy H 1 receptor antagonists 1 st generation 2 nd generation Decongestants Oral Topical Leukotriene receptor antagonists Anticholinergic medications Mast Cell Stabilizers Immunomodulators Steroids Systemic Topical Monoclonal Antibodies Anti-IgE Anti-IL Pharmacotherapy Pathways of Allergic Inflammation Therapy Sneezing Rhinorrhea Congestion Nasal Itching Eye Symptoms H 1 receptor antagonist Decongestants Intranasal corticosteroids Leukotriene receptor antagonist Anticholinergic Cromolyn sodium Arachidonic Acid Pathway Antihistamines First Generation Competitive H 1 binding Lipophilic (crosses the BBB) Anticholinergic effect (urinary retention, xerostomia) Diphenhydramine, chlorpheniramine, hydroxyzine Second Generation Non-competitive H 1 binding Lipophobic (less sedation, improved performance) Minimal anticholinergic activity Terfenadine, fexofenadine, loratadine (des), azelastine, cetirizine (levo) Cardiac effects (macrolides, systemic antifungals) 2
3 Effects of Antihistamines Decongestants Early phase Nasal congestion from vasodilitation Sneezing from trigeminal irritation Rhinorrhea from vascular permeability Itchiness, airway smooth muscle contraction Late phase Eosinophil recruitment Arachidonic acid mediators Cell adhesion Efficacy Similar between the generations Cetirizine = fexofenadine > loratadine Cognitive impairment Effects on the task of driving: diphen.>etoh>fex=placebo Response time: EtOH>diphen>fex=placebo Testing scores in children (10-12): non-atopic>loratadine>diphen Effects of the late phase on learning Pharmacology Sympathomimetic effect Binds to alpha-1 and alpha-2 receptors Displaced norepinephrine from receptors Blocks the reuptake of norepinephrine Topical decongestants Systemic decongestants Topical Decongestants Rapid onset of action (<5 minutes) Duration approximately 6 hours Local potency greater than with systemic Risks rhinitis medicamentosa (>7 days) Choices: Generic (Trade) Phenylephrine (Neo-synephrine ) Oxymetazoline (Afrin, Dristan ) Naphazoline (Privine ) Epinephrine (Primatene ) Cocaine (Coke, Blow, Nose Candy, etc) Systemic Decongestants Stimulates alpha-1 and beta receptors Levels peak - 2 hours (½ life 3-4 hours) Urinary clearance May produce urinary retention or insomnia Less chance of rebound effect Use with caution in patients with a history of: HTN, CAD, glaucoma, hyperthyroidism, MAO inhibitor use, urinary retention, CVA Pseudoephendrine is only available choice Corticosteroids Systemic, injected or topical Binds to intracellular receptors (mrna, protein) Prevents initiation of the allergic cascade and down-regulates the response Decreased recruitment and migration of eosinophils Increased apoptosis of eosinophils Decreased activity of basophils and mast cells Decreased migration of APC, T-cells, B-cells Decreased cytokine expression Topical Corticosteroids Non-sedating Low systemic bioavailability Onset of action can take up to 7 days Best used in the AM for children Major side effects include HA, nosebleeds Posterior subcapsular cataracts not proven Use when congestion is a major symptom Chronic use leads to growth suppression in children without HPA suppression All are pregnancy category C 3
4 Leukotrienes Initially identified in the 1930 s called the slow reacting substances of anaphylaxis (SRS-A) Finally isolated in 1983 Produced locally by: eosinophils, basophils, mast cells, APC Effects of cysteinyl leukotrienes (C 4,D 4,E 4 ) Wheal and flare reaction Increased bronchoconstriction LTE 4 attracts neutro, eos in asthmatic patients Leukotriene Receptor Antagonists Indicated for the treatment of asthma 2003: gained the indication for AR Montelukast is available in the U.S. Improvement in nasal symptom scores Combination with antihistamine has been found to have additive effect. Low side effect profile - Isolated cases of liver toxicity and Churg-Strauss syndrome with certain members of this class. Useful in nasal polyposis +/- ASA triad? Anticholinergic Medications Topical ipratropium bromide (Atrovent ) in a 0.3% and 0.6% pump spray device Decreases parasympathetic tone Improves watery rhinorrhea only Indicated for PAR, PNAR, URI Begin with AM loading dose, repeat in 6 hours if no improvement noted. Use with caution in elderly patients, narrow angle glaucoma or urinary retention. Mast Cell Stabilizers Useful before anticipated antigen exposure QID dosing is difficult to follow Cromolyn sodium (Nasalcrom, Intal ) Went OTC in 1997 Nedocromil (Tilade ) Effects on mast cells Inhibits Ca +2 dependent degranulation Stabilizes mast cell membrane Late phase inhibition of eos and neutrophils Oral Antihistamines Drug Sedation Hepatic Diphenhydramine Renal Pregnancy Category 4+ no no B Loratadine +/- yes yes B Desloratadine no yes yes C Fexofenadine no no no C Cetirizine 1+ yes yes B Topical Nasal Sprays & Montelukast Drug Sedation Hepatic Renal Pregnancy Category Azelastine 1+ no no C Ipratropium no no no B bromide Cromolyn no yes yes B sodium Oxymetazoline no no no C Montelukast no no no B 4
5 Pharmacotherapy Other Modalities Omalizumab (anti-ige monoclonal antibody) Petasites hybridus (Butterbur) Anti-IL-4, Anti-IL-5 antibodies Prostaglandin D 2 receptor antagonists Cobalamins Mucolytics Stepwise Management Plan STEP 1 Mild Intermittent, but noticeable symptoms Try a non-sedating AH ± decongestant or a leukotriene receptor antagonist STEP 2 Moderate persistent, bothersome symptoms Consider intranasal steroid alone or combined STEP 3 Severe Inadequate response to initial therapy Significant impact on the quality of life Co-morbidities are occurring Combined therapy ± oral corticosteroids, antibiotics STEP 4 Step Down Modify medications based on symptoms Take Home Points In general, the lowest effective dose of a medication should be used to minimize side effects You must be aware of side effects, safety profile and drug interactions Medication strategies must be tailored to the individual s needs One size does not fit all You may have to follow a moving target! 5
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