H, antihistaminics

Nevertheless, although the nonsedating H antihistamines have substantially improved the acceptabiUty and clinical efficacy of this class of compounds, these do not provide complete rehef eye disease responds less well than nasal disease, of the rhinitis symptoms nasal congestion responds poorly, breakthrough symptoms occur at high poUen counts, and only some 70% of patients report excellent to good treatment responses. Considerable research therefore still continues in the H antihistamine field. New antihistamines are continually being introduced. 

Histamine Hj-antagonists such as cimetidine or ranitidine can be heipfu when combined with H,-antihistamines... 

Fig. 1.5 Decision tree for the design of non-sedative H]-antihistaminics. Log D is measured at pH 7.4, while Alog P refers to compounds in their neutral state (redrawn from reference [27]).

Motion sickness. Effective prophylaxis can be achieved with the parasympatholytic scopolamine (p. 106) and H antihistamines (p. 114) of the diphenyl-methane type (e.g., diphenhydramine, meclizine). Antiemetic activity is not a property shared by all parasympatho-lytics or antihistamines. The efficacy of the drugs mentioned depends on the actual situation of the in vidual (gastric filling, ethanol consumption), environ-... 

Ranitidine - 50 mg IV over 3 to 5 minutes. May be of value in addition to H- antihistamines, although this opinion is not universally shared. 

IgE-medlated release of mast cell contents. Inset, Intact mast cell with histamine stored In granules. An IgE antibody molecule Is depicted adjacent to the mast cell. Two IgE molecules combine with a mast cell (sensitization). The attachment of an antigen (allergen) to the sensitized mast cell Initiates release of histamine (and other substances) from the mast cell. This degranulation can be prevented by such agents as isoproterenol, theophylline, epinephrine, and cromolyn sodium. H antihistamines do not interfere with degranulation but instead prevent actions of histamine at various pharmacological receptors. 

Clinical analyses confirmed that topic glucocorticoids as well as most H, antihistamines, especially of the 3rd generation, are able to inhibit the upreg-ulation of ICAM-1 on epithelial cells during early and late phases of allergic inflammation [11, 12],... 

In case of an obstruction of the nasal airways, the swelling should first be reduced and then the patient should apply the anti-inflammatory medication to ensure its necessary distribution over the complete mucosa. Antihistamines in addition to oral therapy may also be applied locally, intranasally or conjunctivally. The combination of all three substance groups (H, antihistamines, topic glucocorticoids and antileukotrienes) as a pretreatment as well as a symptomatic treatment during immunotherapy increases the chances of success of hyposensitization in our experience [unpubl. data]. 

Nicholson AN, Handford AD, Turner C, Stone BM. Studies on performance and sleepiness with the H,-antihistamine, desloratadine. Aviat Space Environ Med 2003 74(8) 809-l 5. 

Uses. The H,-antihistamines are used for symptomatic relief of allergies such as hay fever and urticaria (see below). They are of broadly similar therapeutic efficacy. 

Reboxetine. Most of the activity of rehoxetine resides in the 5.5 isomer (The marketed compound is RR and 55.) It is claimed to he superior to fluoxetine in severe depression. It is marketed in Europe. At least three tricyclic compounds, desipramine. nortriptyline, and the technically tetracyclic maprotiline are SNERIs. They, of course, have typical characteristic TCA side effects but lower anticholinergic and H -antihistaminic (sedative) effects than dimethyl compounds. SNERIs arc clinically effective antidepressants. 

Cetirizine is the primary acid metabolite of hydroxyzine, resulting from complete oxidation of the primary alcohol moiety. This compound is zwittcrionic and relatively polar and thus does not penetrate the BBB readily. Before its introduction in the United States, ectiri/ine was one of the most widely prescribed H antihistamines in Europe. It is highly selective in its interaction with various hormonal binding sites and highly potent ( terfenadinc) as well. " - "... 

Most antihistamines have anticholinergic atropine-like actions and cause a dry mouth and similar side-effects. The clinical uses of H, antihistamines are extensive, particularly for the symptomatic relief of allergy, such as hay fever and urticaria, and (together with corticosteroids) in the acute treatment of anaphylactic shock. Many antihistamines also have antinauseant properties and are used, for instance, to prevent travel sickness (though this property may well result from their anticholinergic actions). The older antihistamines produce drowsiness and this sedative action may be used to help sleep (e.g. promethazine). 

Brzezinska, E., Koska, G. and Wimezak, A. (2003) Application of thin-layer chromatographic data in quantitative structure-activity relationship assay of thiazole and benzothiazole derivatives with H-antihistamine activity. II. J. Chromat., 1007, 157-164. 

Cyproheptadine is also a potent H, antihistamine (Chapter 13). In addition, it exhibits antimuscarinic and sedative effects. Kitanserin is an inhibitor of peripheral 5-HT2 receptors, and it exhibits postsynaptic at antagonism as well. It is unlikely to have psychotropic activity because of its peripheral nature. 

The synthesis of a series of triazolobenzopyranones carrying piperazinoalkoxy substituents on the phenyl ring demonstrated the feasibility of integrating the mast-cell-stabilizing properties of the chromone (benzopyranone) moiety and H( antihistaminic properties into one molecule. The most effective compound of a small series was BR-28390. Its antihistaminic potency (guinea pig ileum) was the same as mepyramine histamine release inhibition effectiveness (tested by rat passive peritoneal anaphylaxis) was somewhat less than cromolyn. 

Describe the pharmacology of the two generations and three subgroups of H, antihistamines list prototypical agents for each subgroup. 

Loratadine Second-generation H, antihistamine used in hay fever. Tox Much less seda-... 

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