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1、Histamine,REPORTER: 2006级麻醉学研究生 向 凯,Histamine,Describe the physiology of histamine and clinical uses of histamine receptor antagonists Histamine is a biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter.,This some
2、what called histame hytpsensitivity,Histamine,Low MW amine Natural endogenous(内源的,内生的) substance Produces intense physiologic effects Locally Systemically Present in mast cells located Skin Lungs Gastrointestinal (胃肠的)tract No CNS effects evident,Histamine: Synthesis,Occurs in tissues Decarboxylatio
3、n(脱羧） of histidine（组氨酸） Stored in vesicles in a complex with heparin Stored histamine is released in response to antigen-antibody reactions,Histamine: Mechanism of Action,Released from storage cells by: Chemical insult Physical insult Mechanism involves a high intracellular（细胞内的） calcium concentrati
4、on Release can be inhibited by high intracellular levels of cAMP Histamine acts via specific cell surface receptors,Histamine Effects on Organ Systems,Cardiovascular system Dilates fine vessels of the microcirculation Increasing capillary permeability（渗透性） Decrease in BP Capillary and arteriolar dil
5、ation Positive inotropic and chronotropic effects Direct H-2 receptor stimulation,Histamine Effects on Organ Systems,Extravascular smooth muscle H-1 receptors in bronchial smooth muscle Decreased lung capacity H-1 receptors in GI smooth muscle Spasmodic contractions,Histamine Effects on Organ System
6、s,H-2 receptors in parietal cells Increased gastric H+ secretion Evokes copious secretion of gastric fluid, pepsin, intrinsic factor of Castle Contains high concentration of H+ Increased gastric H+ secretion results from direct stimulating effect of histamine on parietal cell,Histamine Effects on Or
7、gan Systems,Dermal Classic wheal and flare response of skin Increased capillary permeability Increased vasodilatation（血管舒张） Immunologic Major mediator of type I hypersensitivity rxns,H-1 Receptors,Mediate histamine-induced contraction of smooth muscle in GI and bronchi Mediate a delay in the conduct
8、ion of cardiac impulses through the AV node,H-2 Receptors,Mediate histamine-induced secretion of gastric hydrogen ions (H+) Mediate increased myocardial contractility and HR H-2 receptors are present in the CNS,H-3 Receptors histamine,Function as autoreceptors Inhibit synthesis and release of hisami
9、ne,Histamine Physiologic Role,Increased gastric sections Allergic reaction & anaphylactic shock Tissue repair & growth Neurotransmission Regulation of microcirculation,Histamine Untoward Effects,Vasodilatation producing Decrease BP Flushing Tachycardia（心动过速） Skin temperature increase HA / Visual dis
10、turbances Smooth muscle contractions Dyspnea Diarrhea,Risk Factors for Histaminoid Reactions,History of histaminoid reactions Reactions rare in children Reaction occur more frequently in young adults Peak incidence fourth decade Females affected more than males Neuromuscular blocking agents No evide
11、nce that anxious patients react more frequently Reactions to latex common with neural tube defects,Intra-operative Anaphylaxis,Intra-operative Anaphylaxis 70% Neuromuscular blocking agents 12.5% Latex 4.6% Colloids（胶体，胶质） 3.6% Hypnotic agents 2.6% Antibiotics,Tests for Histaminoid Reactions,Skin tes
12、ts Intradermal skin tests Prick test Leucocyte histamine releasing test Allergen specific IGE,Skin test,Treatment,Aimed at modulating effects of released mediators and inhibiting mediator production and release Stop the cause of histaminoid reaction Oxygen 100% Early intubation Epinephrineto manage
13、hypotension, bronchospasm （支气管痉挛） and angioedema 1 ml of a 1:10000 solution IV, repeated every minute until a satisfactory clinical response,Treatment,Second therapy - antihistamines Catecholamine（儿荼酚胺） infusions Inhaled bronchodilators（支气管舒张药） Corticosteroids In the presence of sympathetic block by
14、 either blockers or regional anesthesia, reactions are usually refractory to treatment. High-dose dopamine or other adrenoreceptor agonists may be required. Steroids ineffective in the acute reaction.,Histamine Receptor Antagonists,H1 and H2 receptor antagonists Do not inhibit release of histamine A
15、ttach to receptors and prevent responses mediated by histamine,H1 Receptor Antagonist,Bronchial smooth muscle Intestinal smooth muscle Small blood vessels Sensory impulses for itching Resemble histamine Contain a substituted ethylamine Unlike histamine Contain a tertiary amino group linked to two ar
16、omatic substituents,Anti-histame medicines,H1 Receptor Antagonists: Pharmacokinetics,Readily absorbed from GI tract Maximal plasma concentrations in 1 to 2 hours Elimination half-life is about 3.5 hours Extensive liver metabolism And there is still a lot of H-receptor Antagonists to make you known,If you are interested ,please contact me.,Thanks!,
