上海交通大学：《药理学 Pharmacology》课程教学资源（讲义课件）Histamine &H-R blocking drugs

上游充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 漏 Histamine &H-R blocking drugs A八VGHA7 IAOTON CH2-CH2一NH HN

Histamine &H-R blocking drugs

上浒充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 introduction Histamine is widely distributed in body tissues;its functions as a neurotransmitter and neuromodulator. histidine histamine c00- storage mast cell and basophils allergy、 stimulate NO TONG release histamine◆H-R

introduction Histamine is widely distributed in body tissues; its functions as a neurotransmitter and neuromodulator. histidine coo￾histamine storage mast cell and basophils allergy、 stimulate release histamine H-R

上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 H-R distributing and effects type tissue effect antagonist H SM(bronchial,GI...) （+) diphenhydramine, dermal vessel (+) promethazine... atria,A-V node conduction H2 parietal cell secretion个 cimetidine, vessel 1回() ranitidine... ventricle,SA node HR个 H3 central and peripheral feedback thioperamide nerves regulation

H-R distributing and effects type tissue effect antagonist H1 SM (bronchial,GI…) (+) diphenhydramine, dermal vessel (+) promethazine… atria, A-V node conduction  H2 parietal cell secretion  cimetidine, vessel (-) ranitidine… ventricle, SA node HR  H3 central and peripheral feedback thioperamide nerves regulation

上浒充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Effects of Histamine 1.Cardiovascular system: 1)Cardiac effects:increased contractility and increased pacemaker rate.-mediated chiefly by H2-R. But H-R mediates the decrease of conductility in human atrial muscle. 2)Vascular effects:vasodilator action (H-R,H2-R). endothelial cells contraction and increased permeability (H-R)

Effects of Histamine 1. Cardiovascular system: 1) Cardiac effects: increased contractility and increased pacemaker rate.——mediated chiefly by H2 -R. But H1 -R mediates the decrease of conductility in human atrial muscle. 2) Vascular effects: vasodilator action ( H1 -R, H2 -R). endothelial cells contraction and increased permeability ( H1 -R)

上降充通大粤 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Effects of Histamine 2.Nervous system: powerful stimulant of sensory nerve endings,especially those mediating pain and itching. 3.Smooth muscle: contraction (H1-R)-bronchoconstriction,abort 4.Secretory tissues: stimulant of gastric acid secretion(H2-R) 5.The“triple response”: Intradermal injection of histamine causes a characteristic wheal-and-flare response

Effects of Histamine 2. Nervous system: powerful stimulant of sensory nerve endings, especially those mediating pain and itching. 3. Smooth muscle: contraction (H1-R) → bronchoconstriction, abort. 4. Secretory tissues: stimulant of gastric acid secretion (H2 -R) 5. The “triple response”: Intradermal injection of histamine causes a characteristic wheal-and-flare response

为 上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 Antihistamines H-R blocking drugs The first-generations has a relatively strong sedative effects Diphenhydramine Promethazine Tripelennamine TONG UNIVERSITY Chlorpheniramine ●●●●●●

H1 -R blocking drugs The first –generations has a relatively strong sedative effects Diphenhydramine Promethazine Tripelennamine Chlorpheniramine …… Antihistamines

上游充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 H-R blocking drugs The second-generations has less sedative effects and less distribution into the CNS Cetirizine≌ Pheniadamine Astemizole HAI J AO TONG UNIVERSITY V Terfenadine

H1 -R blocking drugs The second-generations has less sedative effects and less distribution into the CNS Cetirizine Pheniadamine Astemizole Terfenadine ……

上游充通大淫 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 H-R blocking drugs common characteristics] 1.the basic structures similar as histamine; -CH2-CH2-N< 2.their action mechanisms are same: competitive blocking H-R; 3.the characteristics of pharmacokinetics are similar: rapidly absorbed by po. metabolized primarily in the liver

H1 -R blocking drugs 【 common characteristics 】 1. the basic structures similar as histamine; -CH2 -CH2 -N 2. their action mechanisms are same: competitive blocking H1 -R; 3. the characteristics of pharmacokinetics are similar: rapidly absorbed by po. metabolized primarily in the liver

上浒充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 H-R blocking c drugs 【Actions and clinical uses】 1.H-R blockage the first used to prevent allergic reactions or treat their symptoms,such as rhinitis,urticaria etc. notice:(inefficiency)allergic shock and bronchial asthma 1 2.Central inhibitions prevention of motion sickness and vestibular disturbances,nausea and vomiting of pregnancy

H1 -R blocking drugs 【Actions and clinical uses】 1. H1 -R blockage the first used to prevent allergic reactions or treat their symptoms, such as rhinitis, urticaria etc. notice: (inefficiency) allergic shock and bronchial asthma 2. Central inhibitions prevention of motion sickness and vestibular disturbances , nausea and vomiting of pregnancy

上浒充通大 SHANGHAI JIAO TONG UNIVERSITY 1896 1920 1987 2006 H-R blocking drugs Adverse reactions】 Sedation,drowsiness; headache,dry mouth... Terfenadine or astemizole may induce arrhythmias (overdosage or long term used). IAO TONG UN

H1 -R blocking drugs • 【Adverse reactions】 Sedation, drowsiness; headache, dry mouth… Terfenadine or astemizole may induce arrhythmias (overdosage or long term used)