Drugs online research references
J Am Acad Dermatol. 1991 Jun;24(6 Pt 2):1084-7.
Treatment of urticaria and angioedema: low-sedating H1-type antihistamines.
Soter NA.
Department of Dermatology, New York University School of Medicine, Charles C. Harris Skin and Cancer Pavilion, New York University Medical Center 10016.
H1-type antihistamines are considered the therapeutic agents of choice for treating urticaria and angioedema. The use of traditional H1 antihistamines is limited by their side effects. In recent years low-sedating H1 antihistamines with reduced sedative and anticholinergic side effects have become popular choices for the treatment of urticaria and angioedema. Terfenadine and astemizole are currently available in the United States, and cetirizine and loratadine, currently under review at the Food and Drug Administration, are available in other countries. Terfenadine, cetirizine, and loratadine achieve rapid peak plasma concentrations in 1 to 2 hours, whereas astemizole has a slow onset of action. In double-blind, placebo-controlled studies of chronic idiopathic urticaria, low-sedating H1 antihistamines were more effective than placebo. The choice of a particular low-sedating H1 antihistamine depends on pharmacokinetic considerations and frequency of administration.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1677011&dopt=Abstract
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J Allergy Clin Immunol. 1991 Jul;88(1):104-13.
The effect of cetirizine on the human isolated bronchus: interaction with salbutamol.
Advenier C, Candenas ML, Naline E, De Vos C.
Faculte de Medecine Paris Ouest, Laboratoire de Pharmacologie, France.
The effects of cetirizine (C), a new generation, nonsedative, H1-antihistamine drug, were studied on human isolated bronchi. C is a potent antagonist of the bronchial muscle contraction induced by histamine, irrespective of whether C is administered by cumulative addition or prophylactically. In the former case, this effect of C was significant at a concentration of 3 X 10(-8) mol/L and was maximal at a concentration of 10(-5) mol/L. The -log of concentration of C causing 50% of the maximal effect induced was 7.30 +/- 0.05 (n = 6), and the effect produced was not significantly modified by bronchial epithelium removal. When C was administered prophylactically, the concentration-response curves to histamine were displaced to the right, but the reduction of maximum histamine response suggests a noncompetitive type of antagonism. C is devoid of notable anticholinergic effects. At concentrations of 10(-8) to 10(-7) mol/L, C proved capable of enhancing the relaxant effect produced by salbutamol (10(-7) to 3 X 10(-7) mol/L) on human isolated bronchi that had been contracted by either histamine or acetylcholine (ACh). The synergy appeared to be additive or potentiating, depending on salbutamol (SAL) concentrations. Under similar conditions, mepyramine does not potentiate the effects of SAL against histamine. Finally, at concentrations of 10(-8) to 10(-6) mol/L, C reduced the functional antagonism observed between SAL and ACh, as can be observed by the increase, in the presence of C, of the maximal relaxant effect of SAL on contractions produced by 10(-3) mol/L of ACh. We may, therefore, conclude that C appears to be a specific antihistamine on human isolated bronchi and that it appears to potentiate the bronchodilator effect of SAL on this preparation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1677016&dopt=Abstract
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Allerg Immunol (Paris). 1991 Feb;23(2):51-7.
[Non-sedative antihistaminics and binding to central and peripheral H1 histamine receptors]
[Article in French]
Leysen JE, Gommeren W, Janssen PF, Sanz G, Gillardin JM, Schotte A, Janssen PA.
Janssen Research Foundation, Beerse, Belgique.
Four non-sedating antihistamines (astemizole, cetirizine, loratadine and terfenadine) were investigated for in vitro and ex vivo binding to histamine-H1 receptors in guinea-pig cerebellum and lung. In vitro, all the drugs dissociated slowly from H1 receptors (half-times greater than or equal to 100 min), Ki,app-values decreased with longer incubation times for potent lipophylic agents (astemizole and terfenadine) Ki,app-values were lower with more dilute tissue suspensions. In optimized assay conditions astemizole showed a Ki,app-value of 0.2 microM. Terfenadine, cetirizine and loratadine bound with 30-, 80- and 100-times lower affinity to H1 receptors. The occupancy of lung and cerebellar H1 receptors was investigated after oral administration of various dosages of the drugs and at several times after drug administration, using ex vivo binding techniques. Astemizole was a very potent compound showing complete differentiation between lung and cerebellar receptor occupation (with 0.63 mg/kg: 70% of lung H1 receptors were occupied, with less than 10% of cerebellar H1 receptor occupancy). A 7-times higher dose of terfenadine was required to induce the same effect. Astemizole produced a rapid and complete occupancy of lung receptors, which was maintained up to 72 h after administration. In contrast, terfenadine produced a peak effect at 1 h and was completely eliminated from lung receptors in 24 h. Loratadine and cetirizine only poorly differentiated between lung and cerebellar receptor occupancy (at 2.5 mg/kg: 70 and 60% of lung receptor occupancy, 50 and 70% of cerebellar receptor occupancy).(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1677249&dopt=Abstract
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