New Insights into the Second Generation Antihistamines

Abstract

Second generation antihistamines are recognised as being highly effective treatments for allergy-based disease and are among the most frequently prescribed and safest drugs in the world. However, consideration of the therapeutic index or the benefit/risk ratio of the H1 receptor antagonists is of paramount importance when prescribing this class of compounds as they are used to treat non-life threatening conditions. There are many second generation antihistamines available and at first examination these appear to be comparable in terms of safety and efficacy. However, the newer antihistamines in fact represent a heterogeneous group of compounds, having markedly differing chemical structures, adverse effects, half-life, tissue distribution and metabolism, spectrum of antihistaminic properties, and varying degrees of anti-inflammatory effects. With regard to the latter, there is growing awareness that some of these compounds might represent useful adjunct medications in asthma therapy. In terms of safety issues, the current second generation grouping includes compounds with proven cardiotoxic effects and others with the potential for adverse drug interactions. Moreover, some of the second generation H1 antagonists have given cause for concern regarding their potential to cause a degree of somnolence in some individuals. It can be argued, therefore, that the present second generation grouping is too large and indistinct since this was based primarily on the concept of separating the first generation sedating compounds from nonsedating H1 antagonists. Although it is too early to talk about a third generation grouping of antihistamines, future membership of such a classification could be based on a low volume of distribution coupled with a lack of sedating effects, drug interactions and cardiotoxicity.

Histamine Directly and Synergistically with Lipopolysaccharide Stimulates Cyclooxygenase-2 Expression and Prostaglandin I2 and E2 Production in Human Coronary Artery Endothelial Cells

“…Human endothelial cells predominantly express H 1 R, which are involved in histamine-mediated hypersensitivity reactions and inflammatory responses (9,31). The present finding that histamine-induced COX-2 expression and PGI 2 production are inhibited by the H 1 R antagonist, fexofenidine, and not by the H 2 R antagonist, famotidine, suggests that histamine-mediated prostanoid homeostasis in HCAEC is regulated via H 1 R activation.…”

Effect of azelastine, montelukast, and their combination on allergen-induced bronchoconstriction in asthma

“…In addition to, or as a consequence of their anti-histaminic activity, anti-histamines might also reduce the release of other mediators, including leukotrienes [23,24]. Azelastine shows many of these properties [25][26][27], among which decreased activation of mast cells coupled with decreased release of cysteinyl leukotrienes seems to be of particular relevance for the present study.…”

Histamine H4and H2Receptors Control Histamine-Induced Interleukin-16 Release from Human CD8+T Cells

“…H 1 receptors are widely expressed throughout the body, with high expression levels being found in the brain, smooth muscle cells, endothelial cells, adrenal medulla, and heart. By controlling smooth muscle and endothelial cell contraction (thereby increasing vascular permeability) and by stimulating nitric oxide formation, H 1 receptors modulate inflammatory and allergic responses; antihistamines have been in clinical use for allergy treatment for decades (reviewed in Walsh et al, 2001). H 2 receptor activation causes cAMP accumulation through activation of a stimulatory G protein in gastric cells stimulating gastric acid secretion (Black et al, 1972).…”