Azelastine, effect

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. 

Geriatric Considerations - Summary Azelastine is a potent H, receptor antagonist with minimal anticholinergic effects, it is used primarily as a nasal spray or ophthalmic solution but is well absorbed and can produce systemic effects such as headache and somnolence. 

Antihistamines currently available for topical ophthalmic use include the first-generation agents pheniramine maleate and antazoline phosphate and the second-generation antihistamines emedastine, azelastine, ketotifen, and olopatadine. The latter three have dual action, which includes a mast cell-stabilizing effect. 

Mast cell stabilizers prevent the mast cell from degranulating and therefore the subsequent release of mediators. However, once the mast cells have already degranulated, mast cell stabilizers are ineffective against the released mediators. Combination drugs with both mast cell-stabilizing and antihistamine effects provide both longterm treatment and a more rapid relief of symptoms. Drugs with this dual-action or multiaction mechanism include azelastine, epinastine, ketotifen, and olopatadine (Table 13-7). 

Olopatadine has been found to be more effective in decreasing itching than epinastine, azelastine, and ketotifen. Although some studies may vary, olopatadine has been found to be preferred over ketotifen in regards to efficacy and comfort. 

Ohya Y, Kumamoto K, Fujishima M. Effects of crossover application of sulindac and azelastine on enalapril-induced cough. J Hum Hypertens 1992 6(l) 81-2. 

In controlled studies, azelastine nasal spray produced a high incidence of itching and burning of the nasal mucosa together with taste disturbance and sometimes unpleasant smell. Sedation does not seem to be frequent in most studies, the frequency of fatigue and drowsiness was not significantly different from placebo. In an open trial in which 119 patients with various types of pruritic dermatoses were treated with oral azelastine, 27 patients reported mild adverse effects such as drowsiness (15 cases, 12.5%) and a bitter after-taste (six cases, 5%). In four patients the treatment was withdrawn because of adverse effects (SEDA-15, 2). 

For seasonal allergic rhinitis, an intranasal antihistamine, aze-lastine, is available. Azelastine has been used successfully in patients who did not respond to loratadine. Using the nasal route offers an alternative to switching to another oral antihistamine. Patient satisfaction has been varied because while the product produces rapid symptom relief, patients complain of drying effects, headache, and diminished effectiveness over time. Patients should be warned of the medication s potential to produce drowsiness, as its systemic availability is approximately 40%. " ... 

A. blocker antihistamines are structurally related to histamine and antagonize the effects of histamine on H., receptor sites. They possess anticholinergic effects (except the nonsedating agents astemizole, azelastine, cetirizine, desloratadine, fexofenadine, loratadine, and terfenadine). They may also stimulate or depress the CNS, and some agents (eg, diphenhydramine) have local anesthetic and membrane-depressant effects in large doses. 

The chemistry of these phthalazines has been better explored than might be expected, probably because of the biological activities possessed by some. For example, the marked bronchodilatory effects of 2-ethyl-4-(pyridin-3-yl)-l(2//)-phthalazinone (209) and 4-(p-chlorobenzyl)-2-(l-methylhexahydro-17/-azepin-4-yl)-l(2//)-phthalazinone hydrochloride (Azelastin) (210) ° led to the synthesis and investigation of a variety of phthalazinone, fused phthalazine, and nonphthalazine analogs as antiasthmatics. " " °° ... 

Ketoconazole raises the levels of desloratadine, emedastine, fexofenadine but as no adverse cardiac effects were seen these combinations are considered safe. No interaction occurs between ketoconazole and azelastine, cetirizine, intranasal levocabastine, and none is expected with levocetirizine. 

Morganroth J, Lyness WH, Perhach JL, Mather GG. Harr JE. Trager WF. Levy RH. Rosenberg A. Lack of effect of azelastine and ketoconazole coadministration on elec trocardiographic parameters in healthy volunteers. J Clin Pharmacol (1997) 37. 1065-72. 

Etesloratadine, emedastine and fexofenadine levels are raised by ketoconazole but because this does not result in adverse cardiac effects concurrent use is considered safe. Azelastine, cetirizine (and therefore probably... 

There is a case of torsade de pointes possibly due to spiramycin with the sedating antihistamine mequitazine. The situation with erythromycin and loratadine is unclear as one study found that the combination caused a very slight increase in QT interval. Both azithromycin and erythromycin raise fexofenadine levels, but this had no effect on the QT interval, or on adverse events. Azelastine, cetirizine, desloratadine, and intranasal levocabastine seem to be free of clinically relevant interactions with macrolides. 

Fexofenadine levels are raised by both azithromycin and erythromycin but because this does not result in adverse cardiac effects concurrent use is considered safe. Azelastine, cetirizine (and therefore probably its isomer levocetirizine) desloratadine and levocabastine seem to be free from clinically significant pharmacokinetic interactions, and have no cardiac effects, and so may therefore provide suitable alternatives if a non-sedating antihistamine is needed in a patient taking macrolides. 

Sale M, Lyness W, Perhach J, Woosley R, Rosenberg A. Lack of effect of coadministration of erythromycin (ERY) with azelastine (AZ) on pharmacokinetics (PK) or... 

Azelastine 2 mg twice daily had no significant effect on the clearance of theophylline 300 mg twice daily in 10 subjects with bronchial asthma. However, one patient had a 20.8% increase and another a 25.3% decrease in clearance. ... 

Asamoto H, Kokura M, Kawakami A, Sasaki Y, FujiiH, Sawano T, Iso S, Ooishi T, Hcdudii Y, Ohara N, Kitamura Y, Morishita H. Effect of azelastine on theophylline clearance in asthma patients. Arerugi (1988) 37, 1033-7. 

An acute anesthetic effect was also confirmed in pigmented Fauve de Bourgogne rabbits, when 0,1% or 0.05% Azelastine ophthalmic solutions were applied. 

When eye drop formulations of the antiallergic Azelastine were tested in both albino and pigmented rabbits a clear hypoesthetic or even anesthetic effect was noted at concentrations of 0.05% or higher. The reduction of the comeal sensitivity was a concentration-dependent, acute, transient effect. However, when Azelastine eye drops were administered repeatedly no changes in the general comeal sensitivity were revealed. Even after a 4-week treatment period with 4 daily applications in pigmented rabbits no relevant differences in the pressure base values were noted. 

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