The Role of Antihistamines in the Management of Allergic Rhinitis

Abstract

Allergic rhinitis is a common disease worldwide and antihistamines remain the mainstay of pharmacotherapy for allergic rhinitis. Histamine is one of main mediators involved in the disease pathophysiology. The primary mechanism of antihistamine action is believed to be competitive antagonism of histamine receptors, specifically the H 1 -receptors. These receptors are present on nerve endings, smooth muscles, and glandular cells. However, H 1 -antagonism may not be their sole mechanism of action. Antihistamines have been used in two forms; oral and topical, in the management of allergic rhinitis. The use of the first-generation oral antihistamines (chlorpheniramine, diphenhydramine, promethazine, tripolidine, clemastine, and tripelennamine) is considerably limited by their sedative and anticholinergic effects. The secondgeneration antihistamines (acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine, mizolastine, and terfenadine) are effective in reducing nasal symptoms, and have no sedative effects. However, terfenadine, astemizole and recently, loratadine, have been found to cause prolongation of the QT interval on electrocardiogram, and can increase the risk for development of potentially lethal ventricular tachyarrhythmias, or torsades de pointes. The next-generation antihistamines (fexofenadine, desloratadine, tecastemizole, and levocetirizine) are typically the structurally modified, active metabolites or isomers of second-generation antihistamines. These agents retain the non-sedating properties of second-generation antihistamines while eliminating or limiting the cardiac risks. Topical antihistamines (azelastine and levocabastine), delivered by nasal spray, avoid or minimize systemic adverse effects. They have a rapid onset of action (less than 15 min) at low drug dosage, but their action is limited to the treated organ.

Use of Antihistamines in Allergic Rhinitis

“…There are four general principles for management of allergy: An optimum pharmacological agent for the treatment of AR meets the following criteria: proven safety and efficacy, an easy route of administration with rapid absorption, rapid onset of action with no side effects and, strong antiallergic activity [11,12]. There are four general principles for management of allergy: An optimum pharmacological agent for the treatment of AR meets the following criteria: proven safety and efficacy, an easy route of administration with rapid absorption, rapid onset of action with no side effects and, strong antiallergic activity [11,12].…”

“…Dale & Laidlaw first studied the physiological effects of histamine and showed that it induced smooth-muscle contraction and vasodilatation in the early 20th century [11,13]. They showed the mechanism between the effect of histamine and the immediate response to an injected outside protein in previously sensitized animals and suggested that histamine might play a role in this reaction.…”

“…Most first-generation H1-antihistamines also have anticholinergic, sedative, local anaesthetic, and antiserotonergic effects that might favourably relieve the symptoms of the AR and also contribute to side-effects [11,13]. These receptors are ready on nerve endings, smooth muscles, and glandular cells.…”

“…H1-receptor antagonists reduce the clinical expression of nasal itching, sneezing, and rhinorrhea, but they are less effective in controlling nasal obstruction [11,12,13]. H1-receptor antagonists reduce the clinical expression of nasal itching, sneezing, and rhinorrhea, but they are less effective in controlling nasal obstruction [11,12,13].…”

“…Despite the high efficacy of the first-generation antihistamines in providing symptomatic relief of allergic rhinitis, urticaria and other disorders, a major limitation of these drugs was that they penetrated the blood-brain barrier readily and caused marked central nervous system side-effects, such as sedation and impaired psychomotor activity, even at therapeutic doses [14]. Side effects of first-generation antihistamines could be explained by two phenomena: (1) they have poor specificity for the H1 receptor and interact with other receptors, and (2) they also cross the blood-brain barrier and interact with various receptors in the CNS [11). The most common and the most important side effects are anticholinergic, including dry mouth and eyes, urinary retention, and central nervous system (CNS) effects, primarily sedation, and impairment of motor and cognitive functions.…”