Pharmacology药理学-浙江大学教学信息化平台

Drugsfortreatmentofrespiratorydiseases HuifangTangDepartmentofpharmacologyZhejiangUniversity schoolofmedicineResearchbuildingC4222012 3 28 Antiasthmaticdrugs Bronchialasthma inflammation bronchoconstriction airwayhyperresponsiveness Antiasthmaticdrugs Airwayinflammation bronchoconstriction Airwayhyperresponsiveness Immunologicalandnon immunologicalstimuli Wheezing asthmaticsymptoms glucocorticosteroidsdisodiumcromoglycateleukotrienemodifiers 2receptoragoniststheophyllinemuscerinicantagonists Antiasthmaticdrugs Airwaypathologicalchangesinpathogenesisofbronchialasthma Antiasthmaticdrugs Airwaypathologicalchangesinpathogenesisofbronchialasthma Drugsusedinthetreatmentofasthma ClassificationinGrashCourse Respiratorysystem 2ndEdition Relievers Bronchodilators 2agonistsshort acting salbutamol terbutalinelong acting salmeterol formoterolAnticholinergics muscarinicantagonists ipratropineXantines theophyllines aminophyllinePreventers Anti inflammatorydrugsGlucocorticosteroids Inhaledsteroids beclomethasone budesonide fluticasoneoralsteroids hydrocortisone prednisone dexamethasoneLeukotriene LT receptorantagonists leukotrienemodifiers LTantagonists montelukast 孟鲁司特 zafirlukast 扎鲁司特 5 lipoxygenaseinhibitors zileuton 齐留通 Inhibitorsofmediatorrelease cromolynsodium nedocromil Antiasthmaticdrugs GlucocorticosteroidsSystemic hydrocortisone氢化可的松prednisone泼尼松dexamethasone地塞米松Inhaled beclomethasonedipropionate二丙酸倍氯米松budesonide布地奈德triamcinoloneacetonide曲安奈德fluticasonepropionate丙酸氟替卡松flunisolide氟尼缩松 Adrenocorticoiddrugs AdrenocorticalhormonesMineralocorticoidsGlucocorticoids Glucocorticosteroids Sexhormones 1 PharmacologicaleffectsMechanismsofglucocorticoidactions 1 Effectsonmetabolisms 2 Permissiveaction 3 Anti inflammatoryeffects 4 Effectsonimmuneandallergy 5 Anti shock 6 Othereffectsantipyreticeffectseffectsonbloodandblood formingorgansskeletalsystemCNSeffects A Glucocorticoiddrugs Mechanismsofglucocorticoidactionsbindingtoglucocorticoidreceptor GR nucleartranslocationbindingtoGRelementregulatingrelatedgenetranscriptionbiologicaleffects usuallyslow A Glucocorticoiddrugs ActionmodeofglucocorticoiddrugsCBG corticosteroidbindingglobulinS glucocorticoidsteroidsGR glucocorticoidreceptorHSP heatshockproteinIP immunophilinGRE glucocorticoid responseelement Examplesofglucocorticoidactions Inhibitionofproinflammatorygenetranscription AP 1andNF B 1 Effectsonmetabolismsa Carbohydrate bloodglucose gluconeogenesis glucoseutilization b Protein synthesis degradation c Lipid plasmacholesterol fatredistribution centralobesity moonface buffalohump d Waterandelectrolytic Na excretion K excretion Ca2 excretion andabsorption A Glucocorticoiddrugs 2 PermissiveactionPotentiatingtheeffectsofcatecholaminesandglucagon 3 Anti inflammatoryeffectsAcute inhibitingmicrovascularleakageleukocyteinfiltrationChronic inhibitingfibroblastproliferationdepositionofcollagencicatrization 瘢痕形成 A Glucocorticoiddrugs Inhibitionofleukocyteinfiltrationandplasmaleakagebyglucocorticoiddrugs a Increasinginflammationrelatedproteinsorenzymesinducinglipocortin inhibitingphospholipaseA2activity decreasingmediators PGs LTs PAFinducingvasocortin decreasingmicrovascularpermeabilityinhibitingtheexpressionofPLA2 COX 2 inducibleNOS etc b Inhibitingcytokinins decreasingthetranscriptionandactivitiesofTNF IL 1 IL 2 IL 5 IL 6 IL 8 etc c Inhibitingadhesionmoleculesd Inducingtheapoptosisofinflammatorycells A Glucocorticoiddrugs 4 EffectsonimmuneandallergySuppressingimmunologicalfunctionsandallergya inducingapoptosisofTandBlymphocytesb inhibitingtranscriptionfactor nuclearfactor B NF B activity A Glucocorticoiddrugs 5 Anti shockSepticshocka improvingcardiovascularfunctionsb inhibitingtheproductionofinflammatoryfactorsc stabilizinglysosomemembrane decreasingthereleaseofmyocardialdepressantfactor MDF d increasingthetolerancetoendotoxinfrombacteria A Glucocorticoiddrugs 6 Othereffectsa antipyreticeffectsb effectsonbloodandblood formingorgansredcell lymphocytes neutrophils function eosinophils platelets c skeletalsystem osteoporosisd CNS increasingexcitability elevatedmood euphoria insomnia restlessness increasedmotoractivity A Glucocorticoiddrugs 2 ADMEandpropertiesofcommonlyuseddrugsCortisoneandprednisonearereducedandtransformedtohydrocortisoneandprednisolone activeforms intheliverMetabolismwillbeincreasedbyhepaticenzymeinductors phenobarbital phenytoin rifampine etc A Glucocorticoiddrugs 3 Clinicaluses 1 Immunediseasesa autoimmunedisorders reumaticfever reumaticcarditis rhumaticarthritis rheumatoidarthritis osteoarthritis systemiclupuserythematosus polyarthritisnodosa nephriticsyndrome etc b rejectionoforgantransplantationc allergicdiseases urticaria serumsickenss contactdermatitis drugallergicreactions chronicsevereasthma statusasthmaticus angioneuroticedema etc A Glucocorticoiddrugs 2 Severeinfectionandinflammationa acutesevereinfections merelysuppressinginflammatorymanifestationsbutattimeslifesavingCausion combinationwitheffectiveantimicrobialdrugs Usuallybenotusedinviralandfungalinfectionsexceptforthosewithcerebraledemaorseveresystemicsymptomsb preventionofsequelaeofsometypesofinflammation suchasinbrain heart eye joint etc A Glucocorticoiddrugs 3 Septicshock largerdose short term combinedwithantimicrobialdrugs 4 Hemologicaldiseases acutelymphocyticleukemia lymphomas aplasticanemia hemolyticanemia leukocytopenia thrombocytopenia etc 5 Topicalapplications skin eye respiratorytract joint localinjection 6 Sometypesoftumors breastandprostaticcancers acutelymphocyticleukemia etc A Glucocorticoiddrugs 4 Adverseeffects 1 Effectsresultingfromcontinuedusedoflargedosesa Hypercorticism likesyndrome centralobesity moonface buffalohump etc hypertension glycosuria hypokalemia etc b Increasingsusceptibilitytoinfections specficantimicrobialdrugsshouldbeadministeredwithGCsc Ingestivesystem pepticulcers etc A Glucocorticoiddrugs d Cardiovascularsystem hypertension arteriosclerosise Myopathyandosteoporosis vertebralcompressionfractures spontaneousfractures especiallyinpostmenopausalwomenf CNS behavioraldisturbances inductionofepilepticseizuresg Inhibitionorarrestofgrowthinchildren A Glucocorticoiddrugs Adverseeffectsofglucocorticoiddrugs Effectsresultingfromcontinuedusedoflargedoses 2 Withdrawalsyndromea Suppressionofhypothalamic pituitary adrenalaxisb Exacerbationoftheunderlyingdiseases rebound 3 Contraindicationspsychiatricdisorders epilepsy activepepticulcers fractures hypercorticism severehypertension diabetesmellitus viralorfungalinfections etc A Glucocorticoiddrugs 5 Applications 1 Replacementtherapy usuallyusinghydrocortisone 2 Promptintensivetreatment i v gtthydrocortisone dexamethasone 3 Long termtherapy oralprednisoneorprednisolonemorningsingledosealternate daytherapyNotes forlesssevereandlesssustainedpatients lesssuppressiononhypothalamic pituitary adrenal HPA axis 4 Tipicalapplications skin eye respiratorytract A Glucocorticoiddrugs Antiasthmaticdrugs Chemicalstructureof4kindsinhalationglucocorticosteroids F O HO C O SCH2F OCOC2H5 CH3 F 丙酸氟替卡松 FP 布地奈德 BUD O HO C O CH2OH O O H C H C3H7 糠酸莫米他松 MF Cl O HO C O Cl O CH3 C O Cl HO C O CH2OCOC2H5 OCOC2H5 CH3 H 二丙酸倍氯米松 BDP O C O CH2OCOC2H5 OCOC2H5 CH3 Beclomethasonedipropionate二丙酸倍氯米松 A Glucocorticoiddrugs 1 PharmacologicaleffectsAntiinflammation inhibitinginflammatorycellactivities antibodyproduction mediatorreleaseInhibitincreasedresponsivenessofthetracheaandbronchi2 ClinicalusesAsfirst linedrugs currentlyControllingchronicsymptomsIneffectiveforacutesymptoms A Glucocorticoiddrugs Adverseeffects Local oropharyngealcandidiasis usingspacerSystemiceffectsHypercorticism likesyndrome centralobesity moonface buffalohump etc hypertension glycosuria hypokalemia etc IncreasingsusceptibilitytoinfectionsIngestivesystem pepticulcers etc Cardiovascularsystem hypertension arteriosclerosisMyopathyandosteoporosis vertebralcompressionfractures spontaneousfractures especiallyinpostmenopausalwomenAdrenalsuppression A Glucocorticoiddrugs B Inhibitorsofmediatorrelease Disodiumcromoglycate色甘酸二钠 cromolyn 色甘酸钠 1 PharmacologicaleffectsInhibitingmediatorreleasefrommastorothercellsInhibitingsensoryneuropeptiderelease2 ClinicalusesPreventionofallergicasthmaActingslowly 2 4weeks 3 AdverseeffectsOropharyngealirritation B Inhibitorsofmediatorrelease CromolynInhibitsmediatorreleasefrommastcells Otherinhibitorsofmediatorrelease Sodiumnedocromil 萘多罗米钠 Inhibitingmediatorsreleasefrommastcellorothercells theeffectisbetterthandisodiumcromoglycate Ketotifen 酮替芬 Inhibitingmediatorsrelease andantagonizingH1receptor B Inhibitorsofmediatorrelease Leukotrienereceptorantagonists LTRA CysLT1receptorantagonist montelukast 孟鲁司特 zafirlukast 扎鲁司特 5 lipoxygenaseinhibitorszileuton 齐留通 C Leukotrienemodifiers Leukotrienemetabolismpathway LTC4 LTD4 LTE4 CysLT1receptorbronchoconstrictors increasemicrovascularpermeability mucussecretionLTB4 BLTreceptorchemoattractantforneutrophils C Leukotrienemodifiers Zafirlukast Accolate 扎鲁司特 anoralLTRAReducingconstrictionoftheairwaysandbuild upofmucusinthelungsandinflammationofthebreathingpassages Clinicaluse twicedailymaintenanc