胃肠病药物治疗课件.ppt

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1、胃肠病药物治疗,上海市消化疾病研究所吴叔明教授,.分类（1）.,抗溃疡 & 胃-食管反流:抗酸药, H2-antigonists, PPI； 膜保护剂, 铋剂,铝制剂 IBD : 5-ASA & 4-ASA, SASP, 急性胰腺炎；胰酶替代剂肝炎：贺普汀Gallstone:,胃肠动力药物（分类2）,止泻药物:胆盐结合药物平滑肌松弛药物抗便秘药物 促动药物抗动力药物,抗幽门螺杆菌药物（分类3）,抗生素,GI 相关药物（分类4）,导泻剂镇静剂硬化剂 止血药物造影剂,生长抑素抗血清素免疫抑制剂: Cy.A, FK506, Corticoteroids,H2-Receptor Antagonist

2、(H2-RA),西米替丁雷尼替丁法莫替丁尼扎替丁罗沙替丁,H2-RA A structural analogue of histamine with an aliphatic side chain attached to an imidazole ring.组胺 cAMP 激活 H，KATPase,西米替丁的用药技巧,抑制基础胃酸分泌 与 H2-receptor可逆结合 快速静脉注射可致心动过缓抗酸药会抑制其口服吸收应激出血使用后不能控制 pH，要考虑败血症可能某些药物低调 cimetidine作用. 男性乳房发育停药 3 months后解决,Ranitidine的技巧,唯一用于治疗GERD的

3、 H2-antagonist (FDA) 未发现抗雄激素作用单分子作用比 cimetidin强 510 倍Ranitidine iv 可使 sGPT升高慢性肝病者使用时生物活性无影响. HP根除治疗时与抗生素合用,Famotidine的技巧,西米替丁的25倍 Ranitidine 的10倍 PU治疗疗效与西米替丁、 Ranitidine相同 对其他药物的血清浓度无影响未发现抗雄激素作用 5%的病人可发生头痛.不影响酒精吸收,质子泵抑制剂（PPI）,奥美拉唑达克普隆畔妥拉唑波立特,质子泵抑制剂(PPI),直接与胃酸分泌的最后一步 H+/K+ adenosinetriphosphatase(ATP

4、ase)结合,强力抑制胃酸分泌。 Omeprazole, Lansolazole, Pantolazole，Pariet,质子泵抑制剂,抑制基础胃酸和最大胃酸分泌由酸敏感包膜包裹 使血清胃泌素升高,质子泵抑制剂使用指症,Zollinger-Ellison综合症反流性食管炎消化性溃疡,铋 剂,铋盐具有止泻、保护胃粘膜和选择性抗菌作用 Tripotassium dicitrato bismuthate/colloidal bismuth subcitrate (TDB/CBS), Bismuth subsalicylate and other preparations,铋 盐,溶液时可部分吸收 p

5、H6时沉淀和受损组织易结合抑制某些细菌生长胃肠蠕动下降,促进胃肠蠕动与蛋白酶鏊合，降低蛋白酶活性Aspirin样作用* CBS抑制HP浓度 25mg/l*Bismuth subsalicylate,铋 盐,指征消化不良、恶心、呕吐、腹泻症状治疗消化性溃疡、慢性胃炎预防胃粘膜损伤Hp根除治疗溃疡性结肠炎?,细胞保护制剂硫糖铝 & 米唑前列醇,硫糖铝,sucrose octasulfate- polyaluminum+ 35% 在低 pH时成为二部分吸收带强的负电荷，与胆汁和蛋白结合防 H+ 反弥散.,不改变pH,对蛋白酶无影响Blocking pepsin bind to ulcer base

6、antibiotical effectcytoprotection (PG dependent or indep),硫糖铝的指征,溃疡病应激相关的粘膜损伤促进 NSAIDs 相关的粘膜损伤,但无预防作用.胆汁反流性胃炎和 GERD.其他: 口腔溃疡, 低血磷, 硫糖铝灌肠,硫糖铝,副反应 : 5% 的病人降低药物的生物活性: tetracycline, ketoconazole, digoxin, quinolone antibiotics, quinidine, theophylline, warfarin, Dilantin, H2-antagonists, penicillamine a

7、nd levothyroxine,Sucralfate的技巧,与Cimetidine 治疗PUD疗效相似,可用于维持治疗 在 CRF,吸烟者和孕妇可替代cimetidine.对 GERD,FD, NSAID、应激等粘膜损伤治疗效果佳.剂量和用法:,米唑前列醇（Misoprostol）(100 ug and 200 ug /tablet),MISOPROSTOL (Synthetic peotaglandin E1 methyl ester analogue),具备前列腺素的生物活性: E and F2 型刺激尿道平活肌收缩 A,E and I 型具血管收缩作用E 型可扩张支气管胃粘膜的E2 a

8、nd I2 调节粘膜血流 (cytoprotection),酸和重碳酸盐分泌,Misoprostol作用机理,与壁细胞受体结合 阻断五肽胃泌素和进餐刺激的胃酸分泌动物模型中降低溃疡发生率对 BP,HR,血小板聚集无影响 无抗性激素作用 降低pH作用较H2-RA小,Misoprostol指征,预防 NSAID引起的粘膜损伤应激相关的粘膜损伤消化性溃疡急性GI出血GERD,Misoprostol,Side effect腹泻(13%),腹痛(7%)流产: 早期.,Misoprostol,诀窍不影响NSAID的吸收 CRF者和老人无须剂量调整小剂量具细胞保护作用 ( BF,mucous and bic

9、arbonate secretion)大剂量抑制酸和蛋白酶分泌预防 NSAID引起的粘膜损伤较西米替丁为佳心血管、血液、内分泌副反应少,幽门螺杆菌感染的药物治疗,上海消化疾病研究所吴叔明,抗菌药物治疗的依据,慢性胃炎十二指肠溃疡:一种感染性疾病,根除细菌后复发率低 淋巴瘤胃癌?,消化性溃疡治疗的进展,1.消化性溃疡现代和传统治疗比较2.幽门螺杆菌感染治疗的现状按药物性质分为：含铋剂的治疗方案含质子泵抑制剂或H2受体阻滞剂（H2RA）按药物组合分为：二联疗法、三联疗法、四联疗法,消化性溃疡现代和传统治疗比较,球溃胃溃,抗溃疡药物治疗46周,症状依然,症状消失,HP检查和治疗,疗效肯定,不需维持治

10、疗,抗溃疡药物治疗812周,愈合者,复查,维持治疗,复查,维持治疗,理想的治疗方案,)HP根除率90%)溃疡愈合迅速，症状消失快)病人依从性好)不产生耐药性)疗程短，治疗简便)价格便宜,全国HP科研协作组推荐方案,PPI+两种抗生素：PPI标准剂量+Cla. 0.25+Amo. 1.0 bid. X1周PPI标准剂量+Cla. 0.5+甲硝唑0.4 bid. X1周铋剂+两种抗生素：铋剂标准剂量+四环素 0.5+甲硝唑0.4 bid. X 2周铋剂标准剂量+ Amo. 0.5 +甲硝唑0.4 bid. X 2周铋剂标准剂量+ Cla. 0.25 +甲硝唑0.4 bid. X 1周,动力药物,M

11、etoclopramide 胃复安Dompenridone吗叮啉Cisapride西沙比利Erythromycin红霉素,Metoclopramide,最早的动力制剂，极大的增强了临床医师治疗胃肠动力改变的能力,胃复安,普鲁卡因酰胺的衍生物多巴胺-receptor阻滞剂 升高 LESP, 促进食管和胃窦蠕动幽门括约肌松弛缩短近端小肠的通过时间,胃复安,指征糖尿病胃轻瘫胃-食管反流化疗引起呕吐小肠X线检查,胃复安,禁忌症肠梗阻胃肠道穿孔癫简嗜铬细胞瘤（Pheochromocytoma）椎体外系症状,胃复安,用法防止化疗引起的呕吐, a 10 mg dose of 12 mg/kg /day is

12、 used, with 0.5 to 1.0 mg/kg given every 3 to 4 hours subsequently while the patient is receiving chemotherapy.,技 巧,糖尿病人注意空腹血糖，调整胰岛素眩晕和CNS性忧郁可因同时服用其他多巴胺受体阻滞剂而加重肌肉震颤可用苯海拉明对抗,吗叮啉,特异性多巴胺受体阻滞剂，无胃复氨的CNS副作用,吗叮啉,药理学峰值: po(13%). & im后 1530 mins. 纳肛后(90%) 12hr. 组织中浓度是血浆浓度的28 times 血浆中90%与蛋白结合脑、乳汁、胎盘中浓度低,吗叮啉,

13、机理胃肠道多巴胺受体亲和力较高食管: LESP 升高到1520 mm Hg 胃底和幽门松弛 胃窦和十二指畅收缩 有利固体和液体食物的排空,吗叮啉,止 吐Providing antagonism of apomophine-induced emesis at the level of the chemoreceptor trigger zone增加胃排空,吗叮啉,指 征减轻胃排空延迟和胃食管反流导致的下列症状: 嗳气,腹胀,饱胀，烧灼感,恶心,呕吐,吗叮啉,副反应CNS:泌乳素升高: FM. 男性乳房发育和阳痿亦有报导。Circulation system:,西沙比利,A benzamide d

14、erivative 无抗多巴胺作用第一个对结肠有促动力作用药物,西沙比利,Pharmacology消化道吸收较好(95%).血浆峰值出现于 1.52 hr.首相代谢 (liver metabolism)血浆中90% 与蛋白结合脑和胎盘中浓度低。动物实验中可进入乳汁,西沙比利,机理通过(5-HT4) receptor非直接胆碱能机制来促进乙酰胆碱的释放.食管: LESP 升高到1520 mm Hg 胃底和幽门松弛 胃窦和十二指畅收缩 结肠:促推进作用小肠: 增加小肠运动的幅度和频率,西沙比利指征,GERD胃瘫痪FD术后盲襻慢性便秘慢性假性肠梗阻,其他 : IBS: 胆汁反流性胃炎 脊髓损伤后肠功

15、能不全 DU 维持治疗.,红霉素,机理 增加胃动素浓度，并直接作用于胃动素受体.,红霉素,胃瘫痪术后应用:IV促进术后胃排空延迟.others: vagatomy, scleroderma, chemotherapy Roux en Y symdromGERD, anorexia nerosa and chronic idiopathic intestinal pseudo-obstruction,Erythromycin,Side effect恶心、呕吐、腹痛和腹泻. 静脉炎.*,诀窍,对 糖尿病者促动力作用尤佳.静脉使用较口服效佳.在其他药物无效时使用.,返流性食管炎,胃食管返流炎的内镜诊

16、断（Allison),鳞状上皮炎症 柱状上皮炎症发红 粘膜表面炎症孤立浅表炎症 急性粘膜糜烂溃疡融合，无狭窄 亚急性局限性溃疡溃疡融合、狭窄、易扩张 慢性穿透性溃疡溃疡融合、狭窄、不易扩张溃疡融合、狭窄、纤维化波及纵隔,返流性食管炎分型（9th WGC),分型 征特 I 稀疏、垂直糜烂或溃疡 II 融合性溃疡 III 溃疡融合成环状 IV 疤痕、狭窄,食管功能检查,1.食管压力测定2.酸返流试验3.酸清除试验4.酸灌注试验5.食管闪烁照相术6.24小时pH监测,溃疡性结肠炎的药物治疗,上海市消化疾病研究所吴叔明教授,炎症性肠病 (IBD),病因不明 疾病难于治疗而易于复发.,Criteria

17、for Severe Colitis,1.Diarrhea: 6 stools/per day or more with macroscopic blood2.Fever: Mean evening temp.37.5C or a temp. of 37.8C on at least 2 days out of 4.3.Erythrocyte sedimentation rate elevation 304.Anemia: Hemoglobin level 90 /min Truelove-Lancet 1974;1:1067,Sulfasalazine (SASP),SASP: 5-amin

18、osalicylic acid(5-ASA) 和 sulfapyridine(SP)二部分 2030% SASP 在上 GI吸收, 经胆汁和尿液排泄肠道细菌将 SASP裂解为 SP和5-ASA脂溶吸收的 SP: side-effect脂溶吸收差的SASP留在结肠,Adverse Effects of Sulfasazine,Dose relatednauseavomitinganorexiafolate mal-ab.Headachealopecia,Not dose relatedskin rashhemolytic anemiaagrannulocytosisfibrosing alveo

19、litishepatitismale infertilitycolitis,溃疡性结肠炎的药物治疗,各种剂型 膜包被 控释型 偶合型Asacol Pentasa Osalazine Claversal Balsalazide Salofalk MesalazineRowasa,Mechanisms of Steroid Action-IBD,Stabilizes lysosomal membranesReduces capillary permeabilityFunction as inhibitors of chemotaxis and phagocytosis Impairs cell-m

20、ediated immunity in experimental models,Administration and Dosage,Oral Dosage TaperingIntravenous Bolus or continuous infusionTopical Position, Dosage, Duration,Commonly Used Glucorticoidds,Equivalent Mineralo- Glucocorticoid Glucocorticoid corticoidDuraton of action Potency Dose(mg) Action Short-ac

21、ting Cortisol 1 20 yes Cortisone 0.8 25 yes Prednisone 4 5 y/no Prednisolone 4 5 y/no Methylpredinisolone 5 4 y/noIntermediate-acting Triamcinolone 5 4 noLong-acting Betamethasone 25 0.60 no Dexamethasone 30 0.75 no,免疫抑制药物,药名 作 用 适应症 不良反应 用量mg/kg.d硫唑嘌呤 干扰嘌呤的 缓解期的 胰腺炎、BM 12 生物合成 维持 抑制，过敏 6-MP 肝内转化 缓解

22、期的 胰腺炎、BM 11.5 硫唑嘌呤 维持 抑制，过敏 环胞素 细胞免役 对皮质激素 肝毒性 口服：5 抑制剂 疗效不好者 静滴: 4,UC直肠炎的治疗,推荐治疗：5ASA栓剂或类固醇灌肠的表面治疗。5-ASA有更高的缓解率，激素布地奈的为首选。23周有所缓解。缓解治疗：缓解后减至23次/周栓剂治疗不耐受者口服SASP或美沙拉嗪,远段溃疡性结肠炎（3040厘米处乙结肠）,轻、中度的早期：5ASA栓剂或类固醇灌肠的表面治疗。夜间灌肠（美沙拉嗪4克/天34周后每3天1次。无效时考虑加用氢考晨间灌肠。口服治疗：每天SASP 1+美沙拉嗪1.2+奥沙拉嗪0.5。无效时每天SASP 46+美沙拉嗪4.

23、8+奥沙拉嗪3。重度：5ASA+强的松4060毫克,左半结肠炎和全结肠炎,治疗效应和剂量相关中度：46克SASP或美沙拉嗪4.8克重度和无效者：强的松4060毫克，710天后减量。,重度和爆发性结肠炎,主治方式：强的松30毫克/BID或甲强龙16毫克TID直肠症状为主：加用5ASA和氢考灌肠类固醇IV1014天无效者：手术或环孢素A治疗。,类固醇治疗无效的UC,最大剂量口服和表面治疗的5-ASA以及类固醇治疗无效者。2/3的这类病人在使用免疫抑制剂后可获缓解。硫唑嘌呤或6-巯基嘌呤50毫克/天渐增至硫唑嘌呤1.5毫克或6-巯基嘌呤1.5毫克/kg/天6个月无效，可改用MTX7.5毫克25毫克，

24、812周见效。,类固醇依赖的UC,类固醇减量后复发病例可应用硫唑嘌呤或6-巯基嘌呤，缓解后撤除类固醇，仍应维持免疫抑制治疗。,Crohns病的药物治疗,口腔Crohns病的治疗,1. 含氢考的甲基纤维素、果胶、或明胶作表面治疗，2/3的病人有效。2.硫糖铝表面治疗。,胃十二指肠Crohns病的治疗,甲基纤维素粒剂包裹的缓释美沙拉嗪（Pentasa）部分在近端小肠释放，可用之。Pentasa无效时，类固醇治疗。类固醇依赖或类固醇无效：可应用硫唑嘌呤或6-巯基嘌呤,活动性回肠炎、回结肠炎和结肠炎,SASP作用有限5-ASA治疗：美沙拉嗪4克/天一般有效。从11.6克/天开始。无改善者加用环丙沙星0

25、.5克，一天二次。5-ASA无反应或伴全身症状：强的松4060毫克/天,Crohns病局灶性腹膜炎的治疗,Crohns病局灶性腹膜炎指患者出现发热、腹痛腹膜刺激症状、白细胞增多。甲硝唑+第二代头孢菌素； 青霉素+庆大霉素是否使用类固醇药物尚有争议,Crohns病小肠梗阻的治疗,胃肠减压+TPN+类固醇治疗无效者手术治疗,Crohns病的维持缓解治疗,Crohns病的维持缓解治疗： 5-ASA、类固醇5-ASA的作用不大类固醇作用不明止泻药支持治疗：上述治疗无反应且无全身症状，洛呱丁胺和消胆胺控制腹泻有效,类固醇无效和依赖的Crohns病,硫唑嘌呤或6-巯基嘌呤：50毫克/天，可每月增加25毫克

26、，直至最大剂量。治疗36个月有效硫唑嘌呤或6-巯基嘌呤无效：MTX或环孢霉素抗肿瘤坏死因子-A嵌合抗体输注,Crohns病瘘管的治疗,复发率高，先试用药物。甲硝唑1020毫克/公斤/天可应用6-巯基嘌呤静注环孢霉素抗肿瘤坏死因子-A嵌合抗体输注,Crohns病肛周病和瘘管的治疗,甲硝唑1020毫克/公斤/天甲硝唑和局部切除无效：可应用6-巯基嘌呤抗肿瘤坏死因子-A嵌合抗体输注,Pearls and Pitfall-IBD,IBD flare during pregnacy IBD flare may be detrimental to the outcome of pregnancy? Ste

27、roid should be used to enhance a favorable outcome:No perinatal or fetal adverse effectsNo fetal 80:72,Pearls and Pitfall-IBD,Patient with either psychiatric disease Not affect the risk of onset and developHypoalbuminemia Reduce the dosage to low side-effect and toxicity (nonprotein-bound steroid) I

28、BD flare during dosage tapering Dosage return to previous high levelNo inprovement in once daily usage Splitting regiment could be tried,Pearls and Pitfall-IBD,Retard growth in child Steroid therapy be avoided in kid 15. Low-dose & alternate-day schedule. IBD may delay linear growth too.Long-term &

29、low-dose Cataractes-yearly ophthalmologic exam Osteopenia-Vit D & calcium intake,食管静脉曲张,EVS EVBL 粘合剂治疗,脂肪肝（非酒精性脂肪肝炎，NASH，1980）,相关的病因：糖尿病、药物、过度饥饿、HBC、高血脂、肥胖、TPN、胃肠短路、肝-豆状核变性。 生化检查：AST/ALT 血糖和甘油三脂 铁蛋白 影响学检查肝脂肪增多。 治疗控制热卡摄入。熊去氧胆酸,乙型肝炎治疗拉米夫定（核苷类似物）,慢性乙型肝炎治疗的有效新药抑制乙肝病毒DNA， HB血清转换， ALT恢复正常 ，改善肝细胞的炎性坏死， 改善或

30、延缓肝纤维化进展,贺普丁,病人选择HBeAg：HBV DNA阳性HBeAb： HBV DNA阳性，有变异者ALT高于正常，胆红素低于50umol/l,贺普丁-治疗目标,HBV DNA 阴转HBeAg-HBeAb转换肝脏生化指标恢复正常减少复发，提高生活质量,贺普丁-疗效判断,显效： HBeAg-HBeAb转换； HBV DNA转阴有效：HBV DNA 阴性，HBeAg- HBeAb未转换，ALT正常无效：未达上述标准者。,贺普丁-疗 程,显效病人继续服用36个月,拉米夫定停药后随访,拉米夫定停药 复查ALT X3月 ALT ALT正常 HBeAg、 HBV DNA ALT、HBeAg（3个月）

31、 阴性 阳性 随访 随访 拉米夫定重新治疗,丙型肝炎,Flaviviridae族的单链RNA病毒，输血后肝炎的主要病因更易引起肝硬化和肝癌。诊断：ELIZA和RT-PCR 治疗干扰素,Octreotide,A long-acting octapeptide analogue of somatostatin,Octreotide,PharmacolotyHalf life time: 90 min.10% is renally excreted, 90% systemically metabolizedInhibiting all gut hormone release Inhibiting n

32、ot pituitary hormone release except growth hormone,Octreotide,IndicationHormone-producing islet cell tumors of GIT: VIPoma, Zollinger-Ellison syndrom, Glucagonoma, Insulinoma Carcinoid syndromPortal hypertension & variceal hemorrhagePancretitis: reducing exocrine secretion,Pearls and Pitfalls,Steato

33、rrhea: Improved with pancrease enzyme supplementsReducing pain in inj. site by heating syringe in palms and slow rate injectionMild hypoglycemia in no DM patient, improvement in glucose control in DMLong action on VIP suppressionGallstones: due to change cholesterol and GB motility,重症胰腺炎的11项早期指标,入院或

34、诊断时1）年龄55岁2）WBC160003）血糖200mg%4）LDH350U/L5）AST250U%,48小时时6）HCT下降10%以上7）BUN升高5mg%血钙低于8ng%PaO260mmHg碱缺失超过4mmol液体积聚量6000ml,急性胰腺炎的CT诊断,CT对重症胰腺炎的早期识别和预后判断有使用价值，“脂肪岛”的出现与继发感染关系密切。,CT分级,A级：正常B级：局限或弥漫的胰腺增大，胰腺内少量液体积聚，轮廓不规则。非出血性腺体增强。C级：胰腺异常显象模糊，条纹样改变。D级：单个胰外液体积聚。E级：两个以上胰外液体积聚F级：大量气体和液体积聚于胰腺和邻近部位，累及腹膜后间隙。,急性胰腺

35、炎,有待证实或有限作用的药物： 抗酸剂、抗胆碱能药物、H2-受体拮抗剂镇静剂、胰高糖素、降钙素、生长抑素、加压素、丙基硫氧嘧啶、抑肽酶、加贝脂、肝素、抗生素、激素、前列腺素,慢性胰腺炎,胰腺炎的分类,1963年马赛分类：急性胰腺炎急性复发性胰腺炎 慢性复发性胰腺炎慢性胰腺炎,慢性胰腺炎的分类,1988年罗马分类1.慢性钙化性胰腺炎；2.慢性阻塞性胰腺炎3.慢性炎症性胰腺炎,慢性胰腺炎的确诊标准,（1a）腹部B超：胰腺组织内有胰石存在（1b）CT：胰腺内钙化，胰石存在（2）ERCP胰管不规则扩张、不均匀；主胰管部分或完全阻塞（3）分泌试验 重碳酸盐胰酶分泌减少（4）组织学检查（5）导管上皮增生不

36、典型增生、囊肿形成,胰脂酶,胰腺外分泌不足导致脂肪泻 慢性胰腺炎导致腹痛,Pancrelipase-Pharmacology,脂酶含量: the basis of product potency for relief of steatorrheapH4不可逆性失活Enteric-coated tablet: the coat dissolved at pH 6. (Poor bioavailability )Coated microspheres in capsule: affected by gastric empty of spheres,Suggested Regimen for Pan

37、creatic Enzyme Replacement,1. Begin with a preparation providing a total of 20,000 to 40,000 lipase units per meal.2. Enteric-coated formulations work well for control or steatorrhea, but the nonenteric release protease better in the duodenum and are preferred for pain control.3. The preparation sho

38、uld be taken at the beginnning of a meal or throughout the meal for mal-absorption 4. for pain control, a nighttime dose be given,Suggested Regimen for Pancreatic Enzyme Replacement,5.If nonenteric-coated enzymes are used and no clinical improvement occurs, add one 500 mg tablet of SB before and aft

39、er meals, and with any nighttime enzymes.6. If there is still no improvement, consider: a. Adding a PPI or an H2-blcker b. Is the Dx correct? c. Small-bowel bacteria overgrowth may be present,Pearls & Pitfall,1. Tx. of stearorrhea is effective with high-lipase microsphere preparations.2.Tx. for pain

40、 relief is best by traditional uncoated preparation with high protease and attention to good acid neutralization.3. Bioavailability of the uncoated is uncertain in postgatrectomy due to rapid gastric empty4. Acid neutralization is important in cystic fibrosis.,Pearls & Pitfall,5. A low-fat diet shou

41、ld be given for severe pancritic insufficiency, if steatorrea is not reversed completely by replacement 6. SB may make the coat dissolved prematurely7. A high-fiber diet makes replacement less effective.8. Measuring Tx. response in 34 Wks later. Steatorrhea improve as malnutrition corrected.,Pearls

42、& Pitfall,9. The magnesium or calcium form soaps with free fatty acids worsening steatorrhea.10. Replacement regimen is a life-long threrapy, No. of tablets, comliance and the cost should be considered.,乳果糖Lactulose,A synthetic disaccharide analogue of lactase acts as a laxative by stimulating colon

43、ic peristalsis.,Lactulose,The most important measures in the management of hepatic encephalopathy are eliminating exogenous sources of ammonia by restricting dietary protein , controlling gastrointestinal bleeding ane reducing the number of ammonia-producing enteric bacteria.,Lactulose,MechnismIt is

44、 hydrolyzed into galactose and fructose by bacteria in colon. The monosaccharides breakdown to hydrogen, lactate, and short free acids .Acids enhanced colonic acidification, stimulated motility,inhibited coliform growth and ammonia production and increased fecal ammonia secretion.,Lactulose,Dosage &

45、 Administration1. 3040 ml 3/d , dosage may be adjusted so that patient produces two or three soft stool per day.2.Enema retention: 300 ml lactulose with 700 ml water or NS is gaven per rectum and held at least 20 mins.,Lactulose,Side Effects Gaseousness, abdominal distention, flatulence, belching, a

46、nd abdominal cramping.,Pearls & Pitfall,Other measurement s should be includedRetention enema may be used for patients at risk of aspiration from CNS abnormality.The addition of neomycin may benefit those who continues manifest CNS changes.Hypokalemia & hypernatremia was noted in chronic use.Cautiou

47、s usage in DM.,Antidiarrheal Agents,Antidiarrheal Agents,Kaolin & PectinNonspecific absorbentOnly subjective benefit in diarrheaNot used in intestinal obstruction or kid 3yearsAbsorbing concomitant medicationElectrolytes disorder sould be noticedPectin(to be dietary fiber) shows inprovement of blood

48、 sugar in DM,Loperamide,A synthetic antidiarrheal narcotic analogue, agonist activity on gut-associated mu-opiate receptorAntisecretory and prolonging gut transitDecreasing water & electrolytes absorbance from gut lumen,Loperamide,IndicationChronic diarrhea associated with IBDAdjunct Tx. of nondysen

49、tric diarrheaPostvahotomy diarrheaDosage48 mg/day, not excess 16 mg per day,Loperamide,Side EffectsConstipation, abdominal pain, distention, bloating, nausea and vomitingCentral Nervous system depression: dorwsiness, dizziness, and fatigue often seen in high dose,Loperamide,Pearls & PitfallsNaloxone

50、 is used for CNS depression caused by loperamide overdoseNever used in acute ulcerative colitis and pseudomembranous enterocolitis, as it is associated with toxic megacolonCombined with antibiotics in traveller抯 diarrhea and bacillary dysentryOption in Tx. of irritable bowel syndrom,Diphenoxylate,A