消化系统药物.

消化系统药物DigestiveSystemAgents•Commongastrointestinalsymptoms–Dyspepsia胃炎–Pepticulcerdisease胃溃疡–Diarrhea泄泻–Constipation便秘抗消化性溃疡药消化性溃疡主要十二指肠溃疡、胃溃疡，其发病系保护与攻击因子失平衡有关。保护因素攻击因子抗消化性溃疡药消化性溃疡主要指发生在胃和十二指肠的慢性溃疡，具有自然缓解和反复发作的特点。临床主要症状：反酸、嗳气、周期性上腹部疼痛。发病机制：损伤胃肠粘膜的攻击因子增强或防御因子减弱所致。TypesofUlcersTypeDuodenalUlcer十二指肠GastricUlcer胃LocationFirstpartofsmallintestineStomachPainUpperabdomen,slightlytoRofmidlineOftenpossibletopointtositeofpainDull&morelikelytooccurwhenstomachisemptyRelievedbyfood&antacidsSameareabutlesswelllocalizedOftenaggravatedbyfood,maybeassociatedwithN&VAppetitereductionPersistent&severesymptomsPrecipitatedbysmokingandNSAIDs吸烟，止痛药胃壁细胞受体胆碱受体（M）胃泌素受体组胺受体（H2）激活受体，开放钙通道，最后激活H+,K+--ATP酶，分泌H+到胃内胃酸分泌↑前列腺素受体前列腺素E，保护胃粘膜.根据胃酸分泌机制：H2-受体拮抗剂H2blockers质子泵抑制剂protonpumpinhibitors中和过量胃酸的抗酸药antacids理想抗酸药应该是作用强、迅速、持久、不吸收、不产气、不引起腹泻或便秘，对粘膜及溃疡面有保护收敛作用。本类药物作用基本相同，主要区别在于吸收程度、作用快慢、持续时间和不良反应。抗酸药抗酸药弱碱性物质，中和胃酸，减轻对胃粘膜的刺激和腐蚀。氢氧化镁：抗酸较强，较快，有轻度致泻作用（MagnesiumHydroxide）氢氧化铝：抗酸较强，缓慢，可致便秘（Aluminiumhydroxide）影响四环素的吸收（形成络合物）。碳酸氢钠：抗酸弱，快而短暂，可吸收，产生CO2。用于酸中毒；碱化血及尿液；很少用于抗胃酸Sodiumbicarbonate一般不单用抗组胺药物•组胺的作用–在20世纪40年代，发现–涉及变态反应，损伤和胃分泌的生理调节•抗组胺药物有效地减弱组胺的许多反应–抗过敏疾病–(现在把这批抗组胺药叫作H1受体拮抗剂)•但不能拮抗胃部组胺对胃酸分泌的促进作用H1受体和H2受体存在组胺受体的两个亚型•H2受体–在胃壁细胞存在–与胃酸分泌有关H2-receptorantagonistsFourFDA-approved:Cimetidine西咪替丁（Tagamet®）Ranitidine雷尼替丁（Zantac®）Famotidine法莫替丁（Pepcid®）Therapeuticeffects:•Promotethehealingofgastricandduodenalulcers(胃和十二指肠溃疡)•Gastroesophagealrefluxdz[GERD](反流性食道炎)•UpperGIbleed[GIB](上消化道出血)•Maybeeffectiveinstressulcers(应激性溃疡)&pepticesophagitis(消化性食道炎)H2-receptorantagonists•H+,K+-ATPase(ProtonPump)inhibitor•Omeprazole奥美拉唑(Prilosec®)Lansoprazole兰索拉唑(Prevacid®)Pantoprazole泮托拉唑并且作用最强、效力长久，选择性高，副作用小质子泵抑制剂ProtonpumpinhibitorsTherapeuticuses•Gastroesophagealrefluxdz[GERD](反流性食道炎),有效率达75~85％。•Pepticulcer（消化性溃疡）,服用1~6月，溃疡愈合率达97％，其它类药物无效用4周，愈合率达90％。•InfectionwithH.pyloriplus(Hp)(幽门螺杆菌感染),幽门螺旋杆菌83%~88％转阴。•UpperGIbleed[GIB](上消化道出血)AgentsUsedininfectionofHelicobacterPylori•幽门螺杆菌（helicobacterpylori，HP）为革兰阴性厌氧菌，•在胃十二指肠的粘液层与粘膜细胞之间生长，可产生多种酶及细胞毒素，使粘膜损伤。•是慢性胃炎、消化性溃疡和胃腺癌等胃部疾患发生发展中的一个重要致病因子。FDA-ApprovedTreatmentRegimensforH.pyloriInfection•Omeprazole20mgb.i.d+Clarithromycin500mgb.i.d+Amoxicillin1gb.i.dfor10days•Lansoprazole30mgb.i.d+Clarithromycin500mgb.i.d+Amoxicillin1gb.i.dfor10days•Bismuthsubsalicylate525mgq.i.d+Metronidazole250mgq.i.d+Tetracycline500mgq.i.d×14days+H2receptorantagonist×4wks电镜下幽门螺杆菌•有何副作用？有何‘困难’？Lacteolforte•乳酸杆菌干燥物，抑制腐败细菌生长、繁殖及防止蛋白质发酵，减少肠内产气，促进消化和止泻作用。•临床应用：消化不良、腹胀Digestives助消化药还有什么其他用途？ClinicalclassificationofdiarrheaTypeMechanismCausesOsmotic渗透性UnabsorbedsoluteLactasedeficit,magnesiumantacidexcessSecretory分泌性IncreasedsecretionofelectrolytesE.Coliinfection,ilealresection,thyroidcancerExudative渗出性Defectiveabsorption,outpouringofmucusand/orbloodUlcerativecolitis,Crohn’sdisease,leukemiaMotilitydisorder传导功能失调DecreasedcontacttimeIrritablebowelsyndrome,diabeticneuropathy见泻止泻？Loperamide洛哌丁胺Loperamide洛哌丁胺•可抑制肠道平滑肌的收缩，减少肠蠕动•各种原因引起的非感染性急、慢性腹泻的对症治疗•Slowsintestinalmotility,allowingabsorptionofelectrolytesandwaterthroughtheintestine•Helpsrelievecrampsanddecreasestoolfrequency•Fortraveler’sdiarrhea,nonspecificacutediarrhea,orchronicdiarrheaassociatedwithinflammatoryboweldisease•Sideeffects:dizziness,constipationLoperamide洛哌丁胺•对于伴有肠道感染的腹泻，必须同时应用有效的抗生素治疗。•不应用于需要避免抑制肠蠕动的患者，尤其是肠梗阻、胃肠胀气或便秘的患者。•腹泻患者常发生水和电解质丧失，应适当补充水和电解质。•用药过程中出现便秘或48小时仍无效者应停药。Lomotil•Atropinesulfate25mcg+diphenoxylateHCl2.5mg地芬诺酯+阿托品•Dose:2tabtds-qds(max:8tab/day)乙酰胆碱acetylcholineDrugtreatmentfordiarrheaKaolin•Adsorbents•Formildnonspecificacutediarrhea•Adsorb吸附everythingintheGItract•Negligiblesystemicabsorption•Sideeffects:constipation,bloating,fullnessOthers:Charcoal,Smecta思密达Smecta•蒙脱石散剂•该药不进入血液循环系统，并连同所固定的攻击因子随消化道自身蠕动排出体外•不改变正常的肠蠕动•成人及儿童急、慢性腹泻•如需服用其它药物，建议与该药间隔一段时间便秘ConstipationCauses:因素•Disease–tumors,hypothyroidism,diabeticneuropathy•Drug–narcoticanalgesics,aluminium-containingantacids,amitriptyline•Psychogenic–depression,eatingdisorders(anorexia),consciouseffortstowithholdstool•Lifestyle–low-fibrediet,inadequateintakeoffluids,avoidingtheurgetoemptythebowelTypeoflaxatives•Bulk-forminglaxativese.gFybogel,fibrosine•Emollientlaxativese.gDocusatesodium•Lubricantlaxativese.gMineraloil•Salinelaxativese.gFleetenema•Hyper-osmoticlaxativese.g.Lactulose,Glycerin•Stimulantlaxativese.gSenna,BisacodylBulk-forminglaxatives•纤维•Consideredsafestamongalllaxatives•Safeforlongtermuse•Worksin1–3days•Sufficientfluidconsumptionisrequired(usuallyaglass)喝足够水•Sideeffects:bloatedness,abdominaldiscomfortLubricantlaxatives•油性Mineraloilcoatsandsoftensstool•Recommendedforpatientswhoneedtoavoidstraining(hemorrhoidsurgery,childbirth).•Normallyshorttermuse短暂用•Cancausepneumoniaifitleaksintothelungs•Notrecommendedfortheelderly,strokevictims,andthosewithswallowingdifficulties•Theyarepronetoaspirate,especiallywhilelyingdownoratbedtimeHyper-osmoticlaxatives•Lactulosetypeisaspecialsugar-likelaxative•Inducebowelmovementsbydrawingwaterintothebowelfromsurroundingbodytissues•Thisprovidesasoftstoolmassandincreasedbowelaction•Oftenusedforlong-term乳