消化系统疾病临床治疗及常用药物.ppt

1、治疗胃肠道疾病药物治疗胃肠道疾病药物 消化系统最常见病有：消化系统最常见病有：慢性胃炎、消化性溃疡、和消化系肿慢性胃炎、消化性溃疡、和消化系肿瘤。瘤。肠易激综合征和功能性消化不良越来肠易激综合征和功能性消化不良越来越受到关注。越受到关注。另外，肝胆系统疾病也是很常见疾病。另外，肝胆系统疾病也是很常见疾病。近年在消化性溃疡的发病机制和治疗近年在消化性溃疡的发病机制和治疗的研究都有了显著进展。幽门螺杆菌在胃的研究都有了显著进展。幽门螺杆菌在胃部疾病发病中的作用有了进一步的认识。部疾病发病中的作用有了进一步的认识。消化性溃疡（消化性溃疡（peptic ulcer）为消化系）为消化系统最常见疾病，发病

2、率约统最常见疾病，发病率约8%10%。为。为一种慢性疾病，可反复发作，病情持续一种慢性疾病，可反复发作，病情持续数年至数十年，可发生于消化道任何部数年至数十年，可发生于消化道任何部位，最多见于胃和十二指肠溃疡。位，最多见于胃和十二指肠溃疡。胃溃胃溃疡疡多位于胃小弯近幽门处，多位于胃小弯近幽门处，十二指肠溃十二指肠溃疡疡一般位于球部。一般位于球部。消化性溃疡消化性溃疡一、病因及发病机制一、病因及发病机制 溃疡病的发病机制过去过于强调胃酸和胃蛋白酶的攻击作用，后来开始重视粘膜屏障、细胞保护因子、局部血液循环等抗溃疡因素。正常情况下两者处于平衡状态，当致溃疡因素作用超过抗溃疡因素，两者不平衡时就易发

3、生溃疡。攻击因子（致溃疡因素）1.胃酸过多：各种刺激引起胃酸和胃蛋白酶分泌，产生自身消化作用。有“无酸不成溃疡”的说法。2.幽门螺杆菌（Helicobacter pylori,Hp）：寄生在胃粘液层之下，破坏粘液层，减弱其保护作用。是溃疡病长期不愈，反复发作的重要因素。3.药物：阿斯匹林及非甾体类抗炎药 4.胆汁和十二指肠液的反流：可破坏胃粘膜，刺激G细胞分泌胃泌素促胃酸分泌。防御因子（抗溃疡因素）1.粘膜屏障：粘液-碳酸氢盐屏障（胃腔中pH常/=3 mm in size with depth,that can involve the stomach(gastric ulcer)or duod

4、enum(duodenal ulcer).The most important contributing factors are Helicobacter pylori,nonsteroidal anti-inflammatory drugs(NSAIDs),acid,and pepsin.Although peptic ulcers produce a variety of symptoms,none is specific for the disease.Severe pain or a rapid increase in pain suggests an ulcer complicati

5、on or another diagnosis;associated dyspepsia symptoms include nausea,bloating,heartburn,and belching.Indeed,peptic ulcers are the most common cause of acute upper GI bleedingH pylori eradication and/or antisecretory therapies are the mainstay of todays treatment strategies.四、治疗溃疡病药物分类四、治疗溃疡病药物分类（一）治

6、疗溃疡病药物的评价治疗溃疡病主要有4个有目的：（1）控制症状；（2）促进溃疡愈合；（3）防止并发症发生；（4）防止溃疡复发。现今的所有抗溃疡药物均能达到（1）和（2）的目的，有的还可减少并发症，如出血，穿孔等。但现有的抗溃疡药物都不能彻底根治溃疡病，而杀灭幽门螺旋杆菌的药物能大大降低复发率。抗酸剂：氢氧化铝，三硅酸镁，碳酸钙等，起中和胃酸作用，现已很少用。抑制胃酸分泌：H2受体阻断剂：西咪替西，雷尼替丁，法莫替丁H+-K+-ATP酶抑制剂（质子泵抑制剂）：奥美拉唑，兰索拉唑其他还有M受体阻断剂和胃泌素受体阻断剂胃粘膜保护剂：前列腺素E，枸橼酸铋钾，硫糖铝杀灭幽门螺杆菌：三联疗法：枸橼酸铋、甲硝

7、唑、羟氨苄青霉素二联疗法：奥美拉唑、甲红霉素，或加羟氨苄青霉素三联疗法Acid Peptic Diseases Pharmacological Approach to Treatmenthttp:/ Modulating Gastric Acid抗酸药物的发展Beginning with antacids,histamine type-2 receptor antagonists(H2RAs),and sucralfate,there has been a steady development of effective therapies for these conditions,culmin

8、ating with the proton-pump inhibitors(PPIs)Antacids现已用得越来越少了，大多被H2RAs和PPIs取代。特点：They are inexpensive,readily available,and safe in most populations.Antacids work nearly instantaneously and find utility for rapid relief of mild or sporadic symptoms.The effective time for antacids to reduce stomach ac

9、idity is relatively short on an empty stomach.calcium carbonate,sodium bicarbonate,magnesium hydroxide and aluminum hydroxide.hydrotalcite铝碳酸镁H2-receptor AntagonistsThe H2RAs are reversible structural analogs of histamine that cause a decrease in the tonic activation rate of the receptor,thus,these

10、agents act as inverse agonists with a functional antagonism of histamine activity.Cimetidine,ranitidine,famotidine and nizatidine.（西咪替丁为肝药酶抑制剂，有抗雄激素作用）特点：H2RAs mainly inhibit basal rate of acid release during nonfeeding periods.This is of particular importance during the nocturnal periods of fasting

11、,which is the rational for the use of H2RA dosing at bedtime.The H2RAs are often administered once a day prior to bedtime to maximally impact nocturnal basal acid secretion.All agents have linear pharmacokinetics and are eliminated primarily by renal mechanisms.Dose adjustments are needed for patien

12、ts with renal impairment.H2RAs are superior to placebo,but inferior to PPIs for the treatment of esophageal reflux disease.Histamine receptor antagonists have modest efficacy in nonulcer dyspepsia,however,they are not as effective as PPIs.Proton Pump InhibitorsPPIs are weak bases that act as prodrug

13、s and need an acidic environment in order to inhibit the H+K+-ATPase.PPIs accumulate in the secretory canaliculus of the parietal cell.The PPI becomes protonated and converted into the active sulfenamide species,which forms disulfide bonds with cysteine residues in the-subunit of the H+K+-ATPase.By

14、contrast,with H2RAs,PPIs also decrease pepsin secretion,which serves to reduce mucosal damage.Morning dosing of PPIs is associated with significantly improved acid suppression.PPIs should be administered before breakfast.The effects of the PPIs increase with repeated administration and,generally by

15、the third day.PPIs undergo metabolism via hepatic CYP2C19.Of the PPIs,rabeprazole is unique as only 15-20%of its metabolism involves the CYP system.There is differential metabolism between individuals due to pharmacogenetic variation.Possible associations with hip fractures,renal complications and c

16、ommunity-acquired pneumonia have also been demonstrated.The long-term safety of the class include prolonged hypergastrinemia,the possible association of PPIs with gastric atrophy and chronic hypochlorhydria.PPIs should not be administered concomitantly with H2-antagonists,prostaglandins or other antisecretory agents owing to the marked reduction in their acid inhibitory effects when administered simultaneously.Mucosal Protective AgentsSucralfate It is a nonabsorbable medication that binds to gas