临床药理学消化系统ppt课件

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Acid Peptic Diseases Pharmacological Approach to Treatment
• http://www.medscape.com/viewarticle/7054 18
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Drugs 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,
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This image shows a benign gastric ulcer as seen with a barium study. Note the typical location (lesser curvature), with the ulcer projecting beyond the contour of the stomach.
• Cimetidine, ranitidine, famotidine and
nizatidine. （西咪替丁为肝药酶抑制剂，有抗雄激
素作用）
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• 特点：
– H2RAs mainly inhibit basal rate of acid release during nonfeeding periods. This is of particular importance during the nocturnal periods of fasting, 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.
• 穿孔：急性穿孔可产生休克、腹膜炎，为腹部 外科急症，大多需手术治疗。慢性穿孔可在局 部形成炎症包裹（常见于后壁）。
• 幽门梗阻：因炎症水肿及幽门痉挛或瘢痕狭窄 而至。
• 癌变：只发生在胃溃疡，十二指肠溃疡一般不 会发生恶变。
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Left : An elderly patient presents with melena and hypotension.
二、诊断依据
典型的临床表现只作为诊断的参考， 确诊依赖于纤维胃镜和上消化道钡餐检 查。
• 钡餐造影：直接征象：龛影、浓钡点。
间接征象：变形、激惹等。
• 胃镜：溃疡、周围粘膜肿胀、出血点。 • 查幽门螺杆菌
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三、主要并发症
• 出血：主要由溃疡边缘及基底部血管被侵蚀出 血。轻者大便潜血，重者大出血危及生命。
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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生溃疡。
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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。
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二、主要临床表现
周期性上腹部疼痛，返酸、嗳气、烧心、 腹胀等。
疼痛有规律性，其特点为：
• 周期性：疼痛发生和缓解交替，疼痛数天至数周， 缓解数月。多发生在春秋季
• 反复性：反复发作，不易痊愈。 • 节律性：十二指肠溃疡——饥饿痛，两餐之间，
饭前，夜间痛（上半夜）
胃溃疡——饭后半—1小时左右
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• culminating with the proton-pump inhibitors (PPIs)
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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.
• 抑制胃酸分泌：
▪ H替2丁受体阻断剂：西咪替西，雷尼替丁，法莫
▪ H+-K+-ATP酶抑制剂Βιβλιοθήκη Baidu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
• calcium carbonate, sodium bicarbonate, magnesium hydroxide and aluminum hydroxide. hydrotalcite铝碳酸镁
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H2-receptor Antagonists
• The H2RAs are reversible structural analogs of histamine that cause a decrease in the tonic activation rate of the receptor, thus, these agents act as inverse agonists with a functional antagonism of histamine activity.
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。
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防御因子（抗溃疡因素）
Right : 35-year-old woman presents with tarry stools and a hemoglobin of
75 g/L.
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Gastric ulcer with punched-out ulcer base with whitish fibrinoid exudates.
（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。
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• 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。
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• 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 complication or another diagnosis;
• associated dyspepsia symptoms include nausea, bloating, heartburn, and belching. Indeed, peptic ulcers are the most common cause of acute upper GI bleeding
治疗胃肠道疾病药物
消化系统最常见病有： 慢性胃炎、消化性溃疡、和消化系肿 瘤。 肠易激综合征和功能性消化不良越来 越受到关注。 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 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。
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消化性溃疡
消化性溃疡（peptic ulcer）为消化系 统最常见疾病，发病率约8%~10%。为 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 位，最多见于胃和十二指肠溃疡。胃溃 疡多位于胃小弯近幽门处，十二指肠溃 疡一般位于球部。
• ECL cells synthesize and secrete histamine in response to stimulation by the hormones gastrin and pituitary adenylyl cyclase-activating peptide.
• Together, histamine and gastrin are primary positive regulators of acid secretion from the parietal cell.
1. 粘膜屏障：粘液-碳酸氢盐屏障（胃腔中 pH常<2，粘液下为7），粘膜上皮的紧密 连接。
2. 局部血液循环：
3. 胃肠激素及细胞保护因子：前列腺素，表 皮生长因子
4. 幽门括约肌功能：十二指肠逆蠕动及幽门 松弛
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The acid-peptic diseases
• The acid-peptic diseases are those disorders in which gastric acid and pepsin are necessary, but usually not sufficient, pathogenic factors. While inherently caustic, acid and pepsin in the stomach normally do not produce damage or symptoms because of intrinsic defense mechanisms. Barriers to the reflux of gastric contents into the esophagus comprise the primary esophageal defense. If these protective barriers fail and reflux occurs, dyspepsia and/or erosive esophagitis may result.
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• H pylori eradication and/or antisecretory therapies are the mainstay of today's treatment strategies.
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四、治疗溃疡病药物分类
（一）治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；
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Peptic Ulcer Disease
• Peptic ulcer disease affects 10% of men and 4% of women in the United States at some time in their lives. A peptic ulcer is a mucosal break of >/= 3 mm in size with depth, that can involve the stomach (gastric ulcer) or duodenum (duodenal ulcer). The most important contributing factors are Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs), acid, and pepsin.
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Enterochromaffin-Like (ECL) Cells
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Enterochromaffin-Like (ECL) Cells
• Enterochromaffin-like or ECL cells are a distinctive type of neuroendocrine cell in the gastric mucosa underlying the epithelium. They are most prevalent in the acid-secreting regions of the stomach.
– Antacids work nearly instantaneously and find utility for rapid relief of mild or sporadic symptoms.
– The effective time for antacids to reduce stomach acidity is relatively short on an empty stomach.