胃肠病药物治疗课件

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） n抗溃疡 1:1067 Sulfasalazine (SASP) nSASP: 5-aminosalicylic acid(5-ASA) 和 sulfapyridine(SP)二部分 n2030% SASP 在上 GI吸收, 经胆汁和尿 液排泄 n肠道细菌将 SASP裂解为 SP和5-ASA n脂溶吸收的 SP: side-effect n脂溶吸收差的SASP留在结肠 Adverse Effects of Sulfasazine Dose related nnausea nvomiting nanorexia nfolate mal-ab. nHeadache nalopecia Not dose related nskin rash nhemolytic anemia nagrannulocytosis nfibrosing alveolitis nhepatitis nmale infertility ncolitis 溃疡性结肠炎的药物治疗 n各种剂型 n膜包被 控释型 偶合型 nAsacol Pentasa Osalazine nClaversal Balsalazide nSalofalk Mesalazine nRowasa Mechanisms of Steroid Action-IBD nStabilizes lysosomal membranes nReduces capillary permeability nFunction as inhibitors of chemotaxis and phagocytosis nImpairs cell-mediated immunity in experimental models Administration and Dosage nOral Dosage Tapering nIntravenous Bolus or continuous infusion nTopical Position, Dosage, Duration Commonly Used Glucorticoidds Equivalent Mineralo- Glucocorticoid Glucocorticoid corticoid Duraton of action Potency Dose(mg) Action Short-acting Cortisol 1 20 yes Cortisone 0.8 25 yes Prednisone 4 5 y/no Prednisolone 4 5 y/no Methylpredinisolone 5 4 y/no Intermediate-acting Triamcinolone 5 4 no Long-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 n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。 n缓解治疗：缓解后减至23次/周 n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） n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。 n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4.8+奥沙拉嗪3。 n重度：5ASA+强的松4060毫克 左半结肠炎和全结肠炎 n治疗效应和剂量相关 n中度：46克SASP或美沙拉嗪4.8克 n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 n主治方式：强的松30毫克/BID或甲强龙 16毫克TID n直肠症状为主：加用5ASA和氢考灌肠 n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 n最大剂量口服和表面治疗的5-ASA以及类 固醇治疗无效者。 n2/3的这类病人在使用免疫抑制剂后可获缓 解。 n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 n6个月无效，可改用MTX7.5毫克25毫克， 812周见效。 类固醇依赖的UC n类固醇减量后复发病例 n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 n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 。 nPentasa无效时，类固醇治疗。 n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 nSASP作用有限 n5-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0.5克，一天二次。 n5-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 nCrohns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。 n甲硝唑+第二代头孢菌素； 青霉素+庆大霉素 n是否使用类固醇药物尚有争议 Crohns病小肠梗阻的治疗 n胃肠减压+TPN+类固醇治疗 n无效者手术治疗 Crohns病的维持缓解治疗 nCrohns病的维持缓解治疗： 5-ASA、类 固醇 n5-ASA的作用不大 n类固醇作用不明 n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 n硫唑嘌呤或6-巯基嘌呤：50毫克/天，可 每月增加25毫克，直至最大剂量。 n治疗36个月有效 n硫唑嘌呤或6-巯基嘌呤无效：MTX或环 孢霉素 n抗肿瘤坏死因子-A嵌合抗体输注 Crohns病瘘管的治疗 n复发率高，先试用药物。甲硝唑1020毫 克/公斤/天 n可应用6-巯基嘌呤 n静注环孢霉素 n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 n甲硝唑1020毫克/公斤/天 n甲硝唑和局部切除无效：可应用6-巯基嘌 呤 n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? Steroid should be used to enhance a favorable outcome: nNo perinatal or fetal adverse effects nNo fetal 80:72 Pearls and Pitfall-IBD nPatient with either psychiatric disease Not affect the risk of onset and develop nHypoalbuminemia Reduce the dosage to low side-effect and toxicity (nonprotein-bound steroid) nIBD flare during dosage tapering Dosage return to previous high level nNo inprovement in once daily usage Splitting regiment could be tried Pearls and Pitfall-IBD nRetard growth in child Steroid therapy be avoided in kid 55岁 2）WBC16000 3）血糖200mg% 4）LDH350U/L 5）AST250U% n48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 nA级：正常 nB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。 nC级：胰腺异常显象模糊，条纹样改变。 nD级：单个胰外液体积聚。 nE级：两个以上胰外液体积聚 nF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。 急性胰腺炎 n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： n急性胰腺炎 n急性复发性胰腺炎 n慢性复发性胰腺炎 n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）导管上皮增生不典型增生、囊肿形成 胰脂酶 n胰腺外分泌不足导致脂肪泻 n慢性胰腺炎导致腹痛 Pancrelipase-Pharmacology n脂酶含量: the basis of product potency for relief of steatorrhea npH4不可逆性失活 nEnteric-coated tablet: the coat dissolved at pH 6. (Poor bioavailability ) nCoated microspheres in capsule: affected by gastric empty of spheres Suggested Regimen for Pancreatic 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 should 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 after 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 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 empty 4. Acid neutralization is important in cystic fibrosis. Pearls & Pitfall 5. A low-fat diet should be given for severe pancritic insufficiency, if steatorrea is not reversed completely by replacement 6. SB may make the coat dissolved prematurely 7. A high-fiber diet makes replacement less effective. 8. Measuring Tx. response in 34 Wks later. Steatorrhea improve as malnutrition corrected. Pearls & 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 colonic peristalsis. Lactulose nThe 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 Mechnism nIt is hydrolyzed into galactose and fructose by bacteria in colon. The monosaccharides breakdown to hydrogen, lactate, and short free acids . nAcids enhanced colonic acidification, stimulated motility,inhibited coliform growth and ammonia production and increased fecal ammonia secretion. Lactulose nDosage & Administration 1. 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 nSide Effects Gaseousness, abdominal distention, flatulence, belching, and abdominal cramping. Pearls & Pitfall nOther measurement s should be included nRetention enema may be used for patients at risk of aspiration from CNS abnormality. nThe addition of neomycin may benefit those who continues manifest CNS changes. nHypokalemia & hypernatremia was noted in chronic use. nCautious usage in DM. Antidiarrheal Agents Antidiarrheal Agents Kaolin & Pectin nNonspecific absorbent nOnly subjective benefit in diarrhea nNot used in intestinal obstruction or kid 3years nAbsorbing concomitant medication nElectrolytes disorder sould be noticed nPectin(to be dietary fiber) shows inprovement of blood sugar in DM Loperamide nA synthetic antidiarrheal narcotic analogue, agonist activity on gut- associated mu-opiate receptor nAntisecretory and pro