药理学PPT课件第十五章影响自体活性物质药物

1、药理学PPT课件第十五章影响自体活性物质药物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受体拮抗剂的作用与应用。Histamine and Antihistamine Agents内容组胺：来源，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。Histamine and Antihistamine Agents内容抗组胺药：H1受体阻断剂：对H1受体的阻断作用。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

2、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。Histamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonistsHistamineIntroductionHistamine is biologically active amine that is found in many tissue (such as mast cells or basophils ),has complex ph

3、ysiologic and pathologic effects, and is often released locally. Together with endogenous peptides, prostaglandins and leukotrienes, and cytokines, they are sometimes called autacoids or local hormonesHistamine receptor subtypesReceptor SubtypeDistributionPostreceptor MechanismH1Smooth muscle, endot

4、helium, brain IP3,DAGH2Gastric mucosa, cardiac muscle, mast cells, brain cAMPH3Presynaptic: brain, myenteric plexus, other neuronsG protein-coupledHistamine receptor subtypesReceptor SubtypeEffects after being activatedH1 bronchoconstriction and contraction of intestinal S.M. Expand blood vessel Per

5、meability stimulate sensory nerve endingsH2 Cause gastric acid, gastric pepsin and intrinsic factor production. Cause a decrease in systolic and diastolic blood pressure and a increase in heart rate.Histamine receptor subtypesReceptor SubtypePartially Selective AgonistsPartially Selective Antagonist

6、sH12-(m-Flurophenyl)-histamineDiphenhydramine, promethazine, astemizoleH2Dimaprit, impromidine, amthamineCimetidine, ranitidineH3R-MethylhistamineThioperamideHistaminePharmacodynamics Secretory tissue Smooth muscle Cardiovascular system The “triple response”Receptor SubtypeEffects after being activa

7、tedH1 bronchoconstriction and contraction of intestinal S.M. Expand blood vessel Permeability stimulate sensory nerve endingsH2 Cause gastric acid, gastric pepsin and intrinsic factor production. Cause a decrease in systolic and diastolic blood pressure and a increase in heart rate. The “triple resp

8、onse” 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.HistamineHistamineClinical use of histamine To be used in testing gastric acid secretion and diagnosis of leprosy.

9、Decrease of gastric acid can be seen in malignant anemia and true achlorhydiaHistamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonistsPhysiologic antagonists EpinephrineRelease inhibitors CromolynHistamine receptor antagonists H1

10、receptor antagonists H2 receptor antagonistsHistamine AntagonistsHistamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonistsH1 receptor antagonistsChemistryFirst-generation blockersDiphenhydramine, promethazine, astemizoleSecond-gen

11、eration blockers Cimetidine, ranitidinerapidly absorbed orallywidely distributed and the first-generation drugs enter the CNS readily.Most metabolized in the liver Most excreted from the kidneyPharmacokineticsH1 receptor antagonistsPharmacodynamics Histamine Receptor Blockade CNS Inhibition Antichol

12、inoceptor action and Local anesthesiaReceptor SubtypeEffects after being activatedH1 bronchoconstriction and contraction of intestinal S.M. Expand blood vessel Permeability stimulate sensory nerve endingsH2 Cause gastric acid, gastric pepsin and intrinsic factor production. Cause a decrease in systo

13、lic and diastolic blood pressure and a increase in heart rate.H1 receptor antagonists Allergic Reaction Nausea and Vomiting Sedation and hypnogenesisClinical UsesToxicity Sedation, antimuscarinic action, drug allergy, cardiac arrhythmias (astemizole) and possible teratogenic effects.H1 receptor anta

14、gonistsHistamine and Antihistamine AgentsHistamine and its agonistsHistamine antagonistsH1 receptor antagonistsH2 receptor antagonistsH2 receptor antagonistsChemistry & PharmacokineticsCimetidineRanitidineFamotidineNizatidineH2 receptor antagonistsPharmacodynamicsAcid secretion and gastric motilityC

15、ardiovascular systemimmunological regulationReceptor SubtypeEffects after being activatedH1 bronchoconstriction and contraction of intestinal S.M. Expand blood vessel Permeability stimulate sensory nerve endingsH2 Cause gastric acid, gastric pepsin and intrinsic factor production. Cause a decrease in systolic and diastolic blood pressure and a increase in heart rate.H2 receptor antago