上呼吸道感染药物治疗-课件

Chapter35

Lecture11DrugsforCommonUpperRespiratoryInfections

Chapter35

Lecture11RespiratoryTractUpperrespiratorytractincludes:nares,nasalcavity,pharynx,andlarynx.Lowerrespiratorytractincludes:trachea,bronchi,bronchioles,alveoli,andalveolar-capillarymembraneAirenterstheupperresp.tract&travelstothelowertractwheregasexchangetakesplaceRespiratoryTractUppRespiratoryTractRespiration=theprocesswherebygasexchangeoccursatthealveolar-capillarymembrane.3phases:1.Ventilation-movementofairfromtheatmospherethroughtheupper&lowerairwaystothealveoli2.Perfusion-bloodfromthepulmonarycirculationisadequateatthealveolar-capillarybed3.Diffusion-moleculesmovefromareaofhigherconcentrationtolowerconcentrationofgases-O2passesintothecapillarybedtobecirculated&CO2leavesthecapillarybed&diffusesintothealveoliforvent.excretionRespiratoryTractRespiratRespiratoryTractPerfusion-influencedbyalveolarpressure.Forgasexchange,theperfusionofeachalveolimustbematchedbyadequateventilation.Mucosaledema,secretions,&bronchospasmsincreasetheresistancetoairflow&dec.ventilation&diffusionofgasesBronchialSmoothMuscle-Inthetracheobronchialtubeissmoothmusclewhosefibersspiralaroundthetube

contraction

constrictionofairway-ParasympatheticNervoussystem

releasesacetylcholine

bronchoconstriction-SympatheticNervoussystem

releasesepinephrine

stimulatesbeta-2receptorsinbronchialsmoothmuscle

bronchodilationRespiratoryTractPerfusion-iDrugsforUpperrespiratoryInfectionsUpperRespiratoryInfections(URI’s)=commoncold,acuterhinitis,sinusitis,acutetonsillitis,acutelaryngitis-Thecommoncold=mostexpensive>$500millionspentonOTCpreparationsCommonCold&AcuteRhinitis--Commoncoldcausedbytherhinovirus&affectsprimarilythenasopharyngealtract.-Acuterhinitis(inflammationofmucusmembranesofnose)usuallyaccompaniesthecommoncold-Allergicrhinitis-causedbypollenoraforeignsubstanceDrugsforUpperrespiratoryInDrugsforUpperRespiratoryInfectionsIncubationperiodofacold=1to4daysbeforeonsetofsymptoms&first3daysofthecold-Homeremedies=rest,chickensoup,hottoddies,Vitamins-4groupsofdrugsusedtomanagesymptoms=antihistamins(H-1blocker),decongestants(sympathomimeticamines),antitussives,expectorantsDrugsforUpperRespiratoryInDrugsforUpperRespiratoryInfections-AntihistaminesAntihistaminesorH-1blockers-competew/histamineforreceptorsites

preventsahistamineresponse.2typesofhistaminereceptors-H-1&H-2H-1stimulation=extravascularsmoothmuscles(includingthoseliningnasalcavity)areconstrictedH-2stimulation=aninc.ingastricsecretions=pepticulcerdisease

Donotconfusethe2receptors-antihistaminesdecreasenasopharyngealsecretionsbyblockingtheH-1receptorDrugsforUpperRespiratoryInDrugsforUpperRespiratoryInfections-antihistaminesHistamines-Acompoundderivedfromanaminoacidhistadine.Releasedinresponsetoanallergicrxn(antigen-antibodyrxn)-suchasinhaledpollen-Whenreleaseditreactsw/H-1receptors=arterioles&capillariesdialate=inc.inbldflowtothearea=capillariesbecomemorepermeable=outwardpassageoffluidsintoextracellularspaces=edema(congestion)=releaseofsecretions(runnynose&wateryeyes)-Largeamts.ofreleasedhistamineinanallergicrxn=extensivearteriolardilation=dec.BP,skinflushed&edematous=itching,constriction&spasmofbronchioles=SOB&lg.amts.ofpulmonary&gastricsecretionsDrugsforUpperRespiratoryInDrugsforUpperRespiratoryInfections-AntihistaminesAstemizole(Hismanal),Cetirizine(Zertec),Loratadine(Claritin),Chlorpheniramine(Chlortrimeton),Diphenhydramine(Benadryl)Actions=competitiveantagonistatthehistaminereceptor;somealsohaveanticholinergicpropertiesUses=Treatcolds;perennial/seasonalallergicrhinitis(sneezing,runnynose);allergicactivity(drying&sedation);somearealsoantiemeticSE=Drowsiness,dizziness,sedation,dryingeffectsCI=glaucoma,acuteasthmaDrugsforUpperRespiratoryInDrugsforUpperRespiratoryInfections-DecongestantsNasalcongestionresultsfromdilationofnasalbld.vesselsd/tinfection,inflammation,orallergy.Withdilationthere’stransudationoffluidintotissuespaces

swellingofthenasalcavityDecongestants(sympathomimeticamines)

-stimulatealpha-adrenergicreceptor

vasoconstrictionofcapillariesw/innasalmucosa

shrinkingofthenasalmucusmembranes&reductioninfluidsecretion(runnynose)DrugsforUpperRespiratoryInDrugsforUpperRespiratoryInfections-DecongestantsNaphazolineHCL(Allerest),Pseudoephedrine(Actifed,Sudafed),Oxymetolazone(Afrin),PhenylpropanolamineHCL(Allerest,Dimetapp)Use-Congestiond/tcommoncold,hayfever,upperresp.allergies,sinusitisSE=Jittery,nervous,restless,IncBP,inc.bld.sugarCI=Hypertension,cardiacdisease,diabetesPreparations=nasalspray,tablets,capsules,orliquidFrequentuse,esp.nasalspray,canresultintolerance&reboundnasalcongestion-d/tirritationofnasalmucosaDrugsforUpperRespiratoryInDrugsforUpperRespiratoryInfections-IntranasalGlucocorticoidsBeclomethasone(Beconase,Vancenase,Vanceril),Budesonide(Rhinocort),Dexamethasone(Decadron)fluticasone(Flonase)-Action-steroidsusedtodec.inflammationlocallyinthenose-Use-Perennial/seasonalallergicrhinitis(sneezing,runnynose)-Maybeusedaloneorw/antihistamines-SE-rare,butw/continuoususedrynessofthenasalmucosamayoccurDrugsforUpperRespiratoryInDrugsforUpperRespiratoryInfections-AntitussivesAction-ActsonthecoughcontrolcenterinthemedullatosuppressthecoughreflexUse-Coughsuppressionfornon-productiveirritatingcoughs*Codeine-Narcoticanalgesictocontrolacoughd/tthecommoncoldorbronchitis*Dextromethorphan-nonnarcoticantitussivethatsuppressesthecoughcenterinthemedulla,widelyused-syrup,liquid,chewable&lozenges-SE=drowsiness,sedationDrugsforUpperRespiratoryInDrugsforUpperRespiratoryinfections-ExpectorantsAction-Loosensbronchialsecretionssotheycanbeeliminatedw/coughing*AnonproductivecoughbecomesmoreproductiveandlessfrequentUses-NonproductivecoughsGuaifenesin(Robitussin)=Mostcommon*Usealoneorincombow/otherresp.drugsHydrationisthebestexpectorantDrugsforUpperRespiratoryinChapter36DrugsforAcuteandChronicLowerRespiratoryDisordersChapter36DrugsforAcuteandDrugsforLowerRespiratoryDisordersLungCompliance-Lungvolumebasedontheunitofpressureinthealveoli*Determinesthelung’sabilitytostretch(tissueelasticity)*Determinedby:connectivetissue;surfacetensioninthealveolicontrolledbysurfactant

-surfactantlowerssurfacetensioninalveoli&preventsinterstitialfluidfromentering

*Inc.(high)lungcomplianceinCOPD*Dec.(low)lungcomplianceinrestrictivepulmonarydisease=lungsbecome“stiff”&needmorepressureDrugsforLowerRespiratoryDiDrugsforLowerRespiratoryDisordersChronicobstructedpulmonarydisease(COPD)&restrictivepulmonarydisease=2majorlowerresp.tractdiseasesCOPD=airwayobstructionw/inc.airwayresistancetoairflowtolungtissues-4causes-Chronicbronchitis-emphysema-Bronchiectasis -asthma*Abovefrequentlyresultinirreversiblelungtissuedamage.Asthmareversibleunlessfrequentattacksandbecomeschronic.DrugsforLowerRespiratoryDiDrugsforLowerRespiratoryDisordersRestrictivelungdisease=adec.intotallungcapacityasaresultoffluidaccumulationorlossofelasticityofthelung.*Causes:Pulmonaryedema,pulmonaryfibrosis,pneumonitis,lungtumors,scoliosisBronchialAsthma=10-12millionpeopleofallagesaffected-achronicobstructivepulmonarydiseasecharacterizedbyperiodsofbronchospasmresultinginwheezing&difficultyinbreathingDrugsforLowerRespiratoryDiDrugsforLowerRespiratoryDisordersAsthma-Bronchospasmorbronchoconstrictionresultswhenthelungtissueisexposedtoextrinsicorintrinsicfactorsthatstimulateabronchoconstrictiveresponse

-Causes:humidity,airpressurechanges,temp.changes,smoke,fumes,stress,emotionalupset,allergies,dust,food,somedrugs*Pathophys=Mastcells(foundinconnectivetissuethroughoutthebody)aredirectlyinvolvedintheasthmaticresponse-esp.toextrinsicfactors-allergensattachthemselvestomastcells&basophils=antigen-antibodyrxnDrugsforLowerRespiratoryDi

DrugsforLowerRespiratoryDisorders-AsthmaMastcellsstimulatereleaseofchemicalmediators(histamines,cytokines,serotonin,ECF-A(eosinophils))Thesechemicalmediatorsstimulatebronchialconstriction,mucoussecretions,inflammation,pulmonarycongestionCyclicadenosinemonophosphate(cAMP)-acellularsubstanceresponsibleformaintainingbronchodilation-Wheninhibitedbyhistamines&ECF-A

bronchoconst.Sympathomimetic(adrenergic)bronchodilatorsinc.amt.ofcAMP&promotedilation

firstlinedrugsused

DrugsforLowerRespiratoryDDrugsforLowerRespiratoryDisordersSympathomimetics:Alpha&Beta-2AdrenergicAgonistsIncreasecAMP

dilationofbronchiolesinacutebronchospasmcausedbyanaphylaxisfromallergicrxngivenonselectiveepinephrine

(Adrenalin)-SQinanemergencytopromotebronchodilation&inc.BPSE=tremors,dizziness,HTN,tachycardia,heartpalpitations,anginaForbronchospasmd/tCOPD-selectivebeta-2adrenergicagonistsaregivenviaaerosolortabletDrugsforLowerRespiratoryDiDrugsforLowerRespiratoryDisordersMetaproterenol(Alupent,Metaprel)-somebeta-1,butprimarilyusedasabeta-2agent-POorinhaler/nebulizer-Forlong-termasthmaRxbeta-2adrenergicagonistsfrequentlygivenbyinhalation*moredrugdelivereddirectlytoconstrictedbronchialsite*EffectivedoselessthanPOdose&lesssideeffects-Action=relaxesbronchialsmoothmuscle-onset=fast-SE=Nervousness,tremors,restlessness,insomnia&inc.HR

DrugsforLowerRespiratoryDiDrugsforLowerRespiratoryDisordersAlbuterol(Proventil,Ventolin)-Morebeta-2selective-POorinhaler-Usedforacute/chronicasthma-Rapidonsetofaction&longerdurationthanMetaproterenol-FewerSEbecausemorebeta-2specific,buthighdosescanstilleffectbeta-1receptors&causenervousness,tremors&inc.pulserateDrugsforLowerRespiratoryDiDrugsforLowerRespiratoryDisorders-AnticholinergicsIpratropiumbromide(Atrovent)--Action-competitiveantagonist(inhibits)ofcholinergicreceptorsinbronchialsmoothmuscle=bronchioledilation-Inhaler-Use-Incombinationw/betaagonistforasthma&forbronchospasmassociatedw/COPD-Needtoteachclientshowtouseproperly:IfusingAtroventw/abeta-agonist,usebeta-agonist5min.beforeAtrovent;IfusingAtroventw/aninhaledsteroidorcromolyn,useAtrovent5min.beforethesteroidorcromolyn-bronchiolesdilate&drugsmoreeffective

DrugsforLowerRespiratoryDiDrugsforLowerRespiratoryDisorders-MethylxanthinederivativesAminophylline,Theophylline(TheoDur),Caffeine–*POorIV-*Use-Treatmentofasthma&COPD*Action-Inc.cAMP

bronchodilation;also-diuresis,cardiac,CNS&gastricacidstimulation*WhengivenIV

alowtherapeuticindex&range-Monitorlevelsfrequently*POdosescanbegiveninstandarddosages*Avoidsmoking,caffeine&inc.fluidintakeDrugsforLowerRespiratoryDiMethylxanthinederivativesDrugInteractions:Inctheriskofdigtoxicity,decreasestheeffectstolithium,dectheophyllinlevelswithDilantin,theophyllinandbeta-adrenergicagonistgiventogether-synergisticeffectcanoccurcardiacdysrhythmias.Betablockers,Tagamet,Inderalande-mycindecreasethelivermetabolismrateandinc.thehalf-lifeandeffectsoftheophyllin

SE:Anorexia,N&V,nervousness,dizziness,palpitations,GIupset&bleeding,HA,restlessness,flushing,irritability,markedhypotension,hyper-reflexiaandseizures.CI:Severecardiacdysrhythmias,hyperthyroidism,pepticulcerdisease(increasesgastricsecretions)MethylxanthinederivativesDrDrugsforLowerRespiratoryDisorders-LeukotrineReceptorAntagonists&SynthesisInhibitorsLeukotriene(LT)achemicalmediatorthatcancauseinflammatorychangesinthelung.Thegroupcysteinylleukotrienespromotesandincineosinophilmigration,mucusproduction,andairwaywalledema,whichresultinbroncho-constriction.LTreceptorantagonists<synthesisinhibitors(Leukotrienemodifiers)effectiveinreducingtheinflammatorysymptomsofasthmatriggeredbyallergic&environmentalstimuli-NotforacuteasthmaDrugsforLowerRespiratoryDiLeucotrienereceptorantagonistandsynthesisinhibitorsZafirlukast(Accolate),Zileuton(Zyflo),Montelukastsodium(Singulair)–POAction-DecreasestheinflammatoryprocessUse-prophylactic&maintenancedrugtherapyforasthmaAccolate–1stingroup,leukotrienereceptorantagonistreduceinflammation&decbronchoconstriction,PO-BID-rapidlyabsorbedSingulair–Newleukotrienereceptorantagonist,shortt1/2(2.5-5.5)Safeforchildrenunder6yo.

LeucotrienereceptorantagonisDrugsforLowerRespiratoryDisorders-Glucocorticoids(Steroids)Glococorticoidshaveananti-inflammatoryactionandareusedifasthmaisunresponsivetobronchodilatortherapyGiven:inhaler-beclomethasone(Vanceril,Beclovent);tablet-triamcinolone(Amcort,Aristocory),dexamethasone(Decadron),prednisone;injection-dexamethasone,hydrocortisoneSEsignificantw/long-termoraluse-fluidretention,hyperglycemia,impairedimmuner