组胺(z n)(z n)和抗组胺(z n)(z n)药Histamine and Antihistamine Agents南开大学(nn ki d xu) 医学院张京玲 王侃 代红胜第一页，共三十一页。Histamine and Antihistamine Agents目的 了解组胺与变态反应的关系。掌握抗组胺药H1、H2受体拮抗剂的作用(zuyng)(zuyng)与应用。第二页，共三十一页。Histamine and Antihistamine Agents内容 组胺：来源(liyun)(liyun)，内源性组胺与过敏反应的关系，作用，为诊断用药。H1、H2受体的划分。第三页，共三十一页。Histamine and Antihistamine Agents内容 抗组胺药：H1受体阻断剂：对H1受体的阻断(z(z dun) dun)作用。中枢作用及其它。临床用途，主要不良反应。苯海拉明、异丙嗪（非那根）、氯苯那敏（扑尔敏）、布克利嗪（安其敏）。H2受体阻断剂：对H2受体的阻断作用。西米替丁（甲氰咪呱）的抑酸作用，对消化性溃疡病的评价，不良反应。第四页，共三十一页。Histamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonists第五页，共三十一页。HistamineIntroductionHistamine is biologically active amine that is found in many tissue (such as mast cells or basophils ),has complex physiologic and pathologic effects, and is often released locally. Together with endogenous peptides, prostaglandins and leukotrienes, and cytokines, they are sometimes called autacoids or local hormones第六页，共三十一页。Histamine receptor subtypesReceptor Receptor SubtypeSubtypeDistributionDistributionPostreceptor Postreceptor MechanismMechanismH H1 1Smooth muscle, Smooth muscle, endothelium, brainendothelium, brain IP3,DAG IP3,DAGH H2 2Gastric mucosa, Gastric mucosa, cardiac muscle, cardiac muscle, mast cells, brainmast cells, brain cAMP cAMPH H3 3Presynaptic: brain, Presynaptic: brain, myenteric plexus, myenteric plexus, other neuronsother neuronsG protein-G protein-coupledcoupled第七页，共三十一页。Histamine receptor subtypesReceptor Receptor SubtypeSubtypeEffects after being activatedEffects after being activatedH H1 1 bronchoconstriction and contraction bronchoconstriction and contraction of intestinal S.M. Expand of intestinal S.M. Expand blood vessel Permeabilityblood vessel Permeability stimulate sensory nerve endingsH H2 2 Cause gastric acid, gastric pepsin Cause gastric acid, gastric pepsin and intrinsic factor production.and intrinsic factor production. Cause a decrease in systolic and diastolic blood pressure and a increase in heart rate.第八页，共三十一页。Histamine receptor subtypesReceptor Receptor SubtypeSubtypePartially Selective Partially Selective AgonistsAgonistsPartially Selective Partially Selective AntagonistsAntagonistsH H1 12-(m-Flurophenyl)-2-(m-Flurophenyl)-histaminehistamineDiphenhydramine, Diphenhydramine, promethazine, promethazine, astemizoleastemizoleH H2 2Dimaprit, Dimaprit, impromidine, impromidine, amthamineamthamineCimetidine, Cimetidine, ranitidineranitidineH H3 3R-R-MethylhistamineMethylhistamineThioperamideThioperamide第九页，共三十一页。HistaminePharmacodynamicsSecretory tissueSmooth muscleCardiovascular systemThe “triple response”Receptor Receptor SubtypeSubtypeEffects after being activatedEffects after being activatedH H1 1 bronchoconstriction and contraction bronchoconstriction and contraction of intestinal S.M. of intestinal S.M. Expand blood vessel PermeabilityExpand blood vessel Permeability stimulate sensory nerve endingsH H2 2 Cause gastric acid, gastric pepsin Cause gastric acid, gastric pepsin and intrinsic factor production.and intrinsic factor production. Cause a decrease in systolic and diastolic blood pressure and a increase in heart rate.第十页，共三十一页。The “triple response” Intradermal injection of histamine causes a characteristic wheal-and-flare response, which involves an erythema, an edematous wheal and a red irregular flare surrounding the wheal.第十一页，共三十一页。HistamineHistamineClinical use of histamine To be used in testing gastric acid secretion and diagnosis of leprosy.Decrease of gastric acid can be seen in malignant anemia and true achlorhydia第十二页，共三十一页。Histamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonists第十三页，共三十一页。Physiologic antagonists EpinephrineRelease inhibitors CromolynHistamine receptor antagonists H1 receptor antagonists H2 receptor antagonistsHistamine Antagonists第十四页，共三十一页。Histamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonists第十五页，共三十一页。H1 receptor antagonistsChemistryFirst-generation blockersDiphenhydramine, promethazine Second-generation blockers Astemizole, acrivastine第十六页，共三十一页。urapidly absorbed orallyuwidely distributed and the first-generation drugs enter the CNS readily.uMost metabolized in the liver uMost excreted from the kidneyPharmacokinetics第十七页，共三十一页。H1 receptor antagonistsPharmacodynamicsHistamine Receptor BlockadeCNS InhibitionAnticholinoceptor action and Local anesthesiaReceptor Receptor SubtypeSubtypeEffects after being activatedEffects after being activatedH H1 1 bronchoconstriction and contraction bronchoconstriction and contraction of intestinal S.M. of intestinal S.M. Expand blood vessel PermeabilityExpand blood vessel Permeability stimulate sensory nerve endingsH H2 2 Cause gastric acid, gastric pepsin Cause gastric acid, gastric pepsin and intrinsic factor production.and intrinsic factor production. Cause a decrease in systolic and diastolic blood pressure and a increase in heart rate.第十八页，共三十一页。第十九页，共三十一页。H1 receptor antagonistsAllergic ReactionNausea and VomitingSedation and hypnogenesisClinical Uses第二十页，共三十一页。Toxicity Sedation, antimuscarinic action, drug allergy, cardiac arrhythmias (astemizole) and possible teratogenic effects.H1 receptor antagonists第二十一页，共三十一页。Histamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonists第二十二页，共三十一页。H2 receptor antagonistsChemistry & PharmacokineticsCimetidineRanitidineFamotidineNizatidine第二十三页，共三十一页。H2 receptor antagonistsPharmacodynamicsAcid secretion and gastric motilityCardiovascular systemimmunological regulationReceptor Receptor SubtypeSubtypeEffects after being activatedEffects after being activatedH H1 1 bronchoconstriction and contraction bronchoconstriction and contraction of intestinal S.M. of intestinal S.M. Expand blood vessel PermeabilityExpand blood vessel Permeability stimulate sensory nerve endingsH H2 2 Cause gastric acid, gastric pepsin Cause gastric acid, gastric pepsin and intrinsic factor production.and intrinsic factor production. Cause a decrease in systolic and diastolic blood pressure and a increase in heart rate.第二十四页，共三十一页。第二十五页，共三十一页。第二十六页，共三十一页。第二十七页，共三十一页。H2 receptor antagonistsPeptic Duodenal Ulcer and Gastric ulcerErosive EsophagitisHypersecretory ConditionsClinical Uses第二十八页，共三十一页。H2 receptor antagonistsToxicityGastrointestinal reaction,CNS reaction, Endocrine system reactionCytochrome P-450 inhibition第二十九页，共三十一页。第三十页，共三十一页。内容(nirng)总结组胺(z n)和抗组胺(z n)药Histamine and Antihistamine Agents。苯海拉明、异丙嗪（非那根）、氯苯那敏（扑尔敏）、布克利嗪（安其敏）。2-(m-Flurophenyl)-histamine。Dimaprit, impromidine, amthamine。R-Methylhistamine。Cytochrome P-450 inhibition。THANK YOU第三十一页，共三十一页。