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Chapter26GastrointestinalDrugsDigestivesystemanddiseasesDigestivesystem:
includeesophago,stomach,bowel,liver,courage
andpancreas
etc.Diseasesofdigestivesystem
Commoninclinic,diseasesofisotropyand
functionalityinthisorgans.Antacids
anddrugsusedtotreatpepticulcerdisease
Digestants
LaxativesandantidiarrhealdrugsAntiemetic
drugsAdjuvantdrugusedinliverandgalldiseases--Gallstone-dissolutingdrug
andcholereticdrug
--Drugusedtotreathepaticcoma
ClassificationofdrugsindigestivesystemSection1
Antacids
anddrugusedtotreatpepticulcerdisease
PathogenesisofpepticulcerExcessivesecretionofgastricacidandpepsin(2)InfectionofHelicobacterPylori(幽門螺旋桿菌,HP)(3)Mucosalprotectiveeffectdecreasing
--
gastromucosalfluid(胃粘液)andHCO3—secretion
--prostaglandins(PGs)Drugsusedtotreatpepticulcerdisease1.Gastricacidantisecretorydrugs2.Antacids3.Mucosalprotectiveagents4.Anti-Hpagents1.
GastricacidantisecretorydrugsAcetylcholineHistaminePGE2andPGI2Gastrin
H+、K+-ATPaseGastricacidsecretionbyparietalcellsGastricacidsecretion--acomplexandcontinuousprocess,factorsasfollows:nerve(ACh)---M3-Rparacrine(histamine)---H2-RH+-K+-ATPaseendocrine(gastrin)---CCK2-R
ThereareAChandgastrinreceptorsinenterochromaffin-likecell(腸嗜鉻樣細(xì)胞,ECL).AChandgastrincannotonlystimulateparietalcellsdirectlybutalsoenhancehistaminereleaseandstimulategastricacidsecretionindirectly.----H2-RantagonistcaninhibitgastricacidsecretioninducednotonlybyhistaminebutalsoACh
andgastrin.parietalcells
Protonpumpinhibitors
Omeprazole(奧美拉唑),Lansoprazole(蘭索拉唑),Rabeprazole(雷貝拉唑),Pantoprazole(泮托拉唑),
Esomeprazole(埃索美拉唑).
(1)InhibitorsofH+/K+-ATPase--
InhibitorsofH+/K+-ATPaseorprotonpump,reducegastricacidsecretion
Omeprazole(奧美拉唑,洛賽克,losec)---Changetocompetentsulphonamide
(次磺酰胺)inacidenvironment.TheScombinewiththe–SHofH+/K+-ATPase,H+pumpwasinactivated,andthesecretionofgastricacidwasdecreased
--Increasegastricmucosalbloodflow--inhibitHPpepticulcer:Gastrelcosisandduodenalulcer.(superiortoH2-Rantagonists)Refluxesophagitis(gastroesophagealrefluxdisease,GERD胃食管反流病)Zollinger-Ellisonsyndrome卓-艾綜合癥----inducedbytumorofGastricAntrum(胃竇)Gcellwhichsecretegastrin;---Characteristic:Hypergastrinemia,generousgastricacidsecretion,multipleandrefractoryupperdigestivetractpepticulcer.
ClinicalusesClinicalusesUppergastrointestinalbleeding:pH7.0,easilystopbleedEradicateHP:combinedwithantibioticsClarithromycin克拉霉素,amoxicillin阿莫西林GastrinomaandgastrelcosisinducedbyNSAID.parietalcells
Mechanism:
blockH2-R→reducethesecretionofgastricacid→↓thevolumeofgastricacid&acidityClinicaluses:
①pepticulcer②zollinger-ellisonsyndrome(卓-艾綜合征)③gastroesophagealreflux(胃食管反流)(2)H2-receptorantagonists
Adversereaction:
1)Antiandrogeniceffect:gynecomastia(男子女性型乳房),
impotency,galactorrhea
(溢乳)2)Inhibitliverinducedenzyme:inhibitorsofdrug-metabolizingenzymesInhibitcytochromeP450catalyzedoxidativedrugmetabolismpathway→reduceclearanceofotherdrugsCimetidine(西咪替丁;甲氰咪胍):
400mgbid4W→80%healingRanitidine(雷尼替丁)1)Antisecretiveeffectis10timesthatofCimetidine.2)Lesseffectonhepaticmicrosomalmetabolismsystem.3)LongerdurationandlessantiandrogeniceffectFamotidine(法莫替丁),Nizatidine(尼扎替丁):1)Antisecretiveeffectis30times
thatofCimetidine.2)Havenoeffect
onhepaticmicrosomalmetabolismsystem.Ebrotidine(乙溴替丁):1)↑Expressionofepidermalgrowthfactor(EGF,表皮生長因子)andplatelet-derivedgrowthfactor(PDGF,血小板衍生生長因子)→stimulateproliferationofepithelium2)increasemucussecretion
(2)M1-receptor
antagonistsBlock
M1-receptor
selectively,Inhibitgastricacidsecretion
UsedingastrelcosisandduodenalulcerPirenzepine(哌侖西平)Telenzepine
(替侖西平)BlockGastrinreceptor
InhibitH+pumpReducegastricacidsecretionProtectgastricmucosa
(4)G-receptor
antagonistsProglumide丙谷胺Similarstructurewithgastrin,combinecompetitivelyG-receptorwithgastrinGastrelcosisandduodenalulcerAcuteuppergastrointestinalhemorrhage
Clinicalusage2.Antacids
Weakbases
:Mg(OH)2,MgSiO3,Al(OH)3CaCO3,Ca(HCO3)2,NaHCO3Actions:
1)neutralizegastricacid→reducegastricacidity→reducepepticactivity2)injuryfromH+2.
AntacidsPepticulcerGastroxia(胃酸過多癥)TherapeuticUsesCompoundpreparation(復(fù)方制劑)
isusedoften.
3.MucosalProtectiveAgents
Cellbarrier
GastricmucosalbarriercytomembranetightjunctionresistgastricacidandpepsinReconstructionandregenerationMucosalfluid-HCO3-GlucoproteinandbicarbonatePGs(PGE2、PGI2)
--StimulatePG-receptor,inhibitcAMPdependentcalciumchannel
andH+pump,reducethegastricacidsecretion;PGE2PGI2--Enhancethesecretionofmucosalfluidandbicarbonateby
stomachandduodenalsecretion
--Increasegastricmucosalbloodflow--Protectgastricmucosa--Stimulatereceptor,inhibitthesecretionofgastricacidandpepsin
causedbygastricacid,histamine,gastrin,andfood--Inhibitgastricbleeding,ulcerandnecrosis
causedbyacetylsalicylicacidetc.
Misoprostol米索前列醇
increasethesecretionofgastricmucosalfluidandHCO3—,regionalbloodflowClinicaluses--Gastrelcosisandduodenalulcer--GastrointestinalhemorrhageMechanismsofActionSucralfate
(硫糖鋁)--formingcomplexgelwithmucus,createsaphysicalbarrierthatimpairsdiffusionofHClandpreventsdegradationofmucusbypepsin--adsorb
pepsinandcholalicacid,inhibitactivity--increasethe
secretionofgastricmucosalfluidand
HCO3—
GastrelcosisandduodenalulcerBismuthpotassiumcitrate(枸櫞酸鉍鉀)Protectsgastricmucosa
IncresesPGEreleaseInhibitsHelicobacterpyloriInactivatepepsinMechanismofaction:
1)selectivebindingtoulcer,coatingitandprotectingitfromacidandpepsin.2)inhibitpepsinactivity3)stimulatemucousproduction4)increaseprostaglandinsynthesis.5)antimicrobialactivityagainstHpylori
Gastrelcosisandduodenalulcerwhencombinedwithantibiotics(metronidazole甲硝唑andtetracycline四環(huán)素),ulcerhealingratesofupto98%havebeenseen.clinicalusesColloidalBismuthSubcitrateranitidine枸櫞酸鉍鉀雷尼替丁BismuthPotassiumCitrateranitidineDouble-acting4.Anti-HpagentsHelicobacterpylori(Hp)Agents-Metronidazole甲硝唑-Tetracycline四環(huán)素-Ampicillin氨芐西林-Amoxicillin阿莫西林2005年諾貝爾獎澳大利亞臨床微生物學(xué)家RobinWarren和BarryMarshallSection2Digestants
Dilutehydrochloricacid
PepsinPancreatinDriedyeastBiofermin(乳酶生,lactasin)Compositionofdigestivejuice
AgentsthatenhanceitssecretionSection3
LaxativesandAntidiarrhealDrugs-Increasewater-Softfeces-Promoteenterokinesia-Helpdefecation
Bulklaxative
容積性瀉藥Contactcathartics
接觸性瀉藥Emollientcathartics
潤滑性瀉藥1.
LaxativesBulkLaxative
Magnesiumsulfate
-increasethebulk-increasecholecystokinin(膽囊素)secretion-cholagogueaction(利膽作用)口服后腸道很少吸收,在腸腔內(nèi)形成高滲,增加腸容積而促進(jìn)腸道推進(jìn)性蠕動,產(chǎn)生瀉下作用。Whatisthebulklaxative?SodiumsulfateClinicaluses:obstructivejaundicechroniccholecystitis(慢性膽囊炎)ContactcatharticsPhenolphthalein(酚酞)Anthraquinone(蒽醌)Castoroil(蓖麻油)與腸粘膜接觸,改變腸粘膜的通透性,使電解質(zhì)和水分向腸腔擴散,使腸腔水分增加,蠕動增強,引起瀉下。WhatistheContactcatharticsEmollientcathartics
liquidparaffin(液體石蠟)Glycerin(甘油)2.AntidiarrhealDrugs-Diphenoxylate(地芬諾酯)-medicinalactivatedcharcoal
(活性炭)--absorption-Opiumpreparations-Albumintannate(鞣酸蛋白)--stypsis常見癥狀,可引起疼痛,對毒物的排出有一定保護(hù)作用。但嚴(yán)重的腹瀉,可引起脫水和電解質(zhì)紊亂,應(yīng)適當(dāng)給予止瀉藥以緩解癥狀。能使胃粘膜表面蛋白質(zhì)凝固、沉淀,從而減輕刺激,降低炎性滲出物,發(fā)揮收斂、止瀉作用。DiarrheaSection4Antiemetic
DrugsVestibularfunctionCTZ(chemoreceptortriggerzone)D2,H1,M1,5-HT3
Whydoseapersonvomite?Scopolamine東莨菪堿Benzhydramine苯海拉明Chlorpromazine氯丙嗪Dimenhydrinate乘暈寧Ondansetron
(昂丹司瓊)
:usedinthepreventionofchemotherapy-inducedandpostoperativenauseaandvomiting1.5-HT3-Rinhibitor2.dopaminereceptorantagonists:Metoclopramide(甲氧氯普胺)
Mechanism
1)blockD2-receptorinCTZ2)blockgastrointestinalD-receptor→promotevermiculation腸蠕動
Clinicaluses:
1).Vomiting-Functionaldisorderofgastrointestinaltract-Radiotherapy,operationand
drugs
2)Gastrointestinaltract
hypotonia張力減退Adversereaction:
extrapyramidal(錐體束外的)symptoms,especiallydystonia(張力障礙)--blockDA-receptorofgastrointestinalmuscularlayer
nerveplexus,promotevermiculation(腸蠕動)--de pressthepostsynapse
cholinergicneurondepressanteffect,increaseAChrelease.--difficultlypenetrateBBB,havenoextrapyramidalsymptomsDomperidone(多潘立酮,嗎丁啉)Gastrointestinalprokinetics
Nausea,vomiting-hemicrania偏頭痛-craniocerebraltrauma顱腦損傷-radiationtherapy
GastrointestinaldyskinesiaClinicalUsesCisapride(西沙比利)
stimulate5-HT4-R,
promoteAChreleaseOthers1.
H1receptorblocker:Diphenhydramine苯海拉明,Dimenhydrinate乘暈寧2.Mreceptorblocker:
Scopolamine東莨菪堿3.D2
receptorblockerinCTZChlorpromazine氯丙嗪Section5
Gallstone-dissolutingdrug
andcholereticdrug
Ursodeoxycholicacid(熊去氧膽酸)1.
Lowerthecontentof
cholesterolinbile,
makecholesterol
dissolve
fromthe
surfaceofcalculus.2.
inhibittheabsorptionofcholesterolinintestinaltract3.
Usedin
cholesterolc
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