antihistamines cross the blood-brain barrier, and in usual doses, they potentially cause sedation and impair cognitive function and psychomotor performance.
These medications, some of which have been in use for more than 6 decades, have never been optimally investigated.
Second-generation H antihistamines such as cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine cross the blood-brain barrier to a significantly smaller extent than their predecessors.
The clinical pharmacology, efficacy, and safety of these medications have been extensively studied.
They are therefore the HHistamine, a natural body constituent, is synthesized from L-histidine exclusively by histidine decarboxylase, an enzyme expressed in central nervous system (CNS) neurons, gastric mucosa parietal cells, mast cells, basophils, and other cells throughout the body.
Histamine plays a major role in human health, exerting its diverse effects through 4 or more types of receptors (Table 1).
Through the H receptor, histamine is involved in cell proliferation and differentiation, hematopoiesis, embryonic development, regeneration, and wound healing.
It is a neurotransmitter, has anticonvulsant activity, and contributes to regulation of the sleep-waking cycle, energy and endocrine homeostasis, cognition and memory [↑ Pruritus, pain, vasodilation, vascular permeability, hypotension; flushing, headache, tachycardia, bronchoconstriction, stimulation of airway vagal afferent nerves and cough receptors; ↓ atrioventricular node conduction time↑ Release of histamine and other mediators; ↑ cellular adhesion molecule expression and chemotaxis of eosinophils and neutrophils; ↑ antigen-presenting cell capacity, costimulatory activity on B cells; ↑ cellular immunity (Th1), ↑ autoimmunity; ↓ humoral immunity and Ig E production↑ Eosinophil and neutrophil chemotaxis;↓ IL-12 by dendritic cells; ↑ IL-10 and development of Th2 or tolerance-inducing dendritic cells; ↑ humoral immunity;↓ cellular immunity; suppresses Th2 cells and cytokines; indirect role in allergy, autoimmunity, malignancy, graft rejection receptor, it increases antigen-presenting cell capacity, increases release of histamine and other mediators from mast cells and basophils, up-regulates cellular adhesion molecule expression and chemotaxis of eosinophils and neutrophils, up-regulates Th1 priming and Th1 cell proliferation and interferon- receptor on histaminergic and nonhistaminergic neurons in the central and peripheral nervous systems, it is probably involved in control of neurogenic inflammation through mast cell feedback loops. All 4 types of histamine receptors are heptahelical transmembrane molecules that transduce extracellular signals, by way of G-proteins, to intracellular second messenger systems.
The active and inactive states of these receptors exist in equilibrium; at rest, the inactive state isomerizes with the active state and vice versa [ receptor, either directly or indirectly through nuclear factor-κB, an ubiquitous transcription factor, through which they down-regulate antigen presentation, expression of proinflammatory cytokines and cell adhesion molecules, and chemotaxis.
In addition, through their effects on calcium ion channel activity, H antihistamines have been classified into 6 chemical groups: alkylamines, ethanolamines, ethylenediamines, phenothiazines, piperazines, and piperidines.
Currently, the most commonly used classification system is a functional one, in which H antihistamines are classified as either first-generation medications that readily cross the bloodbrain barrier and potentially sedate and impair cognitive and psychomotor function, or second-generation drugs that cross the blood-brain barrier to a minimal extent and are relatively nonsedating and nonimpairing[ *Acrivastine is related tripolidine.
Cetirizine is a metabolite of hydroxyzine, levocetirizine is an enantiomer of cetirizine, desloratadine is a metabolite of loratadine, and fexofenadine is a metabolite of terfenadine.
**In the United States, these H antihistamines azelastine, emedastine, epinastine, ketotifen, levocabastine, and olopatadine are available in ophthalmic formulations; and azelastine, dimethindene, levocabastine, and olopatadine are available in intranasal formulations.