drjanak
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Mast cells and Antihistaminics
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07.15.08 (1 month ago)
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Basic & Clinical Pharmacology
- 10th Ed. (2007) Edited by Bertram G. Katzung20. Drugs Used in Asthma
LEUKOTRIENE PATHWAY INHIBITORS
Leukotrienes result from the action of 5-lipoxygenase on arachidonic acid and are synthesized by a variety of inflammatory cells in the airways, including eosinophils, mast cells, macrophages, and basophils.
Two approaches to interrupting the leukotriene pathway have been pursued: inhibition of 5-lipoxygenase, thereby preventing leukotriene synthesis; and inhibition of the binding of LTD4 to its receptor on target tissues, thereby preventing its action. Efficacy in blocking airway responses to exercise and to antigen challenge has been shown for drugs in both categories: zileuton, a 5-lipoxygenase inhibitor, and zafirlukast and montelukast, LTD4-receptor antagonists.
Goodman & Gilman's The Pharmacologic Basis of Therapeutics - 11th Ed. (2006)
Zileuton is a potent and selective inhibitor of 5-lipoxygenase activity and thus inhibits the formation of all 5-lipoxygenase products. Thus, in addition to inhibiting the formation of the cys-LTs, zileuton also inhibits the formation of leukotriene B4 (LTB4), a potent chemotactic autacoid, and other eicosanoids that depend on leukotriene A4 (LTA4) synthesis.
Leukotriene-Receptor Antagonists. Cysteinyl leukotrienes (cys-LTs) include leukotriene C4 (LTC4), leukotriene D4 (LTD4), and leukotriene E4 (LTE4). All the cys-LTs are potent constrictors of bronchial smooth muscle. On a molar basis, LTD4 is approximately 1000 times more potent than is histamine as a bronchoconstrictor. Zafirlukast and montelukast are selective high-affinity competitive antagonists for the cys-LT1 receptor
CHAPTER 24. HISTAMINE, BRADYKININ, AND THEIR ANTAGONISTS
Second-Generation Piperidines (Prototype: Terfenadine). Terfenadine and astemizole were withdrawn from the market. Current drugs in this class include loratadine, desloratadine, and fexofenadine. These agents are highly selective for H1 receptors, lack significant anticholinergic actions, and penetrate poorly into the CNS. Taken together, these properties appear to account for the low incidence of side effects of piperidine antihistamines.
Hence Fexofenadine and Ketotifen are anti histamine release agents whilst Zileuton is a potent leukotrine release inhibitor. Zakirlufast is a leukotriene receptor antagonist.
I cannot find any of the 4 given compounds which can be both - inhibitors of histamine release as well as inhibitors of leukotrine release from mast cells.
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