Azelastine

Topical Application. Azelastine (11) and levocabastine (13) have been developed for topical appHcation (45). The topical antihistamines address the preference of some patients for a local treatment and allow adrninistration of dmg directly to the site requited. The advantage of this therapeutic approach is likely to be in the speed of onset of symptom rehef. In contrast to earlier reports of sensitization with older antihistamines locally apphed to the skin (46), sensitization has not been reported with local appHcation to the nose or eyes. 

Azelastine (107) is an antiallergic/antiasthmatic agent prepared from 4-chlorobenzyl-2 -car-boxyphenylketCHie (105) by condensation with hydrazine to give the phthalazinone (106) followed by reaction of the sodium salt of this last with 2-(2-chloroethyl)-N-methylpyrrolidine (presumably involving nucleophilic ring expansion of the bicyclic quaternary salt putatively formed as a first product) to complete the synthesis [30]. 

C,4H2]N20 110406-94-5) see Azelastine benzoic acid 2-(l methyl-4-piperidinyl)hydrazide (CijHujNjO 88858-10-0) see Piperylone benzoic acid (l-methyI-4-piperidylidene)hydrazide (C13H17N3O 92043-04-4) see Piperylone benzoic anhydride... 

C29H42ClN50sSSi2 149681-75-4) see Cladribine 2-[(4-chlarophenyl)acetyl]benzoic acid (C15H11CIO3 53242-76-5) see Azelastine a-chlorophenylacetyl chloride... 

C5Hj 02 140-88-5) see Acrivastine Azelastine Benperidol Benzquinamide Setiptiline Troglitazone ethyl adipoyl chloride... 

C20H27NO4 58115-88-1) see Butorphanol hexahy dro-1 -methyMH-azepin-4-one (C7H13NO 1859-33-2) see Azelastine (3S-trflns)-hexahydro-2-phenyl-l /-pyrroloLl,2-c]imid-azoIe-3-carboxylic acid methyl ester (C14H1KN2O2) see Troglitazone hexahydro-l-(2-propenyl)<4i/-azepin-4-one (CyHi NO) see Talipcxole... 

C],jH2(iN20 65514-97-8) see Nomifensine At-methyl-N-(2-aminobenzyl)phenacylamine (CitHisNjO 119810-30-9) see Nomifensine 4-(methylamino)butanoic acid hydrochloride (C5H,2C1N02 6976-17-6) see Azelastine methyl 3-amino-2-butenoate... 

C2H5NaO 141-52-6) see Azelastine Einorfazone Methyprylon Oseltamivir Pentobarbital Promestriene Propallylonal Protionamide sodium 2-ethylhexanoate... 

Locally acting antihistamines act more quickly than oral agents but need to be administered intranasally at least twice daily due to the potential for removal by nasal secretions.13 Azelastine, an intranasal antihistamine, is as effective as systemic antihistamines in the treatment of perennial and seasonal AR. 

Azelastine acts locally to reduce the same symptoms treated by oral antihistamines it also may reduce nasal congestion to a greater extent. Azelastine is administered twice daily and has a rapid onset of action. Many patients managed with azelastine complain of bitter taste. Drowsiness also has been reported, likely due to systemic absorption.11-13... 

Azelastine nasal spray is indicated for children 5 years of age and older and is considered an alternative to intranasal corticosteroids in patients with persistent severe symptoms. Intranasal cromolyn, another commonly used agent in children, is indicated in patients 2 years of age and older and has an acceptable safety profile. However, limited efficacy and multiple daily administrations limit its use to mild and early rhinitis or for prophylaxis of a known imminent exposure. 

Azelastine Hrreceptor antagonist, mast cell stabilizer May inhibit cytokine release... 

Azelastine 1 drop in affected eye(s) twice daily Ocular stinging, headache, bitter taste... 

Azelastine (Astelin) is an intranasal antihistamine that rapidly relieves symptoms of seasonal allergic rhinitis. However, patients should be cau-... 

Yoneda K, Yamamoto T, Ueta E, Osaki T Suppression by azelastine hydrochloride of NF-kB activation involved in generation of cytokines and nitric oxide. Jpn J Pharmacol 1997 73 145-153. 

AZELASTINE Before initial use, prime the delivery system with 4 sprays or until a fine mist appears. When at least 3 days have elapsed since last use, reprime the pump with 2 sprays or until a fine mist appears. 

Second-generation agents - Intranasal administration of azelastine yields peak levels in 2 to 3 hours, with an elimination half-life of 22 hours. 

Metabolism by the P450 system results in steady-state peak levels of a major active metabolite (desmethylazelastine), which are 20% to 50% of azelastine levels. The elimination half-life of the metabolite is predicted to be 54 hours. The major route of excretion is via feces. ... 

Pregnancy Category B -azatadine, cetirizine, chlorpheniramine, clemastine, cyproheptadine, dexchlorpheniramine, diphenhydramine, loratadine. Category C -azelastine, brompheniramine, carbinoxamine, desloratadine, fexofenadine, hydroxyzine, pheniramine, phenytoloxamine, promethazine, pyrilamine, triprolidine. 

---