Gastrointestinal drugs 基础医学各论 II. Hepatic, pacreatic and biliary disordersHepatic, pacreatic and biliary disorders Ulcer disordersUlcer disorders Abnormal

Gastrointestinal drugsGastrointestinal drugs

基础医学各论 II

•Hepatic, pacreatic Hepatic, pacreatic and biliary disordersand biliary disorders

•Ulcer disordersUlcer disorders

•Abnormal Abnormal mobilitymobility


1.1. Drugs used for peptic ulcersDrugs used for peptic ulcers

2.2. Modulators of gastrointestinal functionsModulators of gastrointestinal functions


Peptic ulcersPeptic ulcers

Pathogenesis of Pathogenesis of peptic ulcerspeptic ulcers

Treatment Treatment approaches approaches

• Infection with gram-Infection with gram-negative Helicobacter negative Helicobacter pyloripylori

• Eradicating H. pylori Eradicating H. pylori infectioninfection

• Increased gastric acid Increased gastric acid secretionsecretion

• Reducing secretion of Reducing secretion of gastric acid or neutralizing gastric acid or neutralizing the acidthe acid

• Inadequate mucosal Inadequate mucosal defense against gastric defense against gastric acid acid

• Protecting the gastric Protecting the gastric mucosa from damagemucosa from damage

SucralfateSucralfatecarbonoxolonecarbonoxolone

misoprostolmisoprostol

Gastric structure related to peptic ulcerGastric structure related to peptic ulcer

Gastric acid secretion and regulationGastric acid secretion and regulation

1. Antacids1. Antacids2. Drugs affecting gastric acid secretion2. Drugs affecting gastric acid secretion• Muscarinic receptor antagonistsMuscarinic receptor antagonists• HH22 receptor antagonists receptor antagonists• HH++-K-K++-ATPase inhibitors (proton pump inhibitors)-ATPase inhibitors (proton pump inhibitors)• Gastrin receptor antagonistsGastrin receptor antagonists3. Mucosal protective drugs3. Mucosal protective drugs4. Antimicrobial drugs (Helicobacter pylori)4. Antimicrobial drugs (Helicobacter pylori)

A. Drugs used for peptic ulcersA. Drugs used for peptic ulcers

Features of antacids Features of antacids

•Basic substances that reduce gastric acidity by neutralizBasic substances that reduce gastric acidity by neutralizing HCling HCl

•The hydroxide is the most common base but trisilicate, The hydroxide is the most common base but trisilicate, carbonate and bicarbonate ions are also used.carbonate and bicarbonate ions are also used.

•Aluminium, magnesium or sodium Aluminium, magnesium or sodium


SucralfateSucralfatecarbonoxolonecarbonoxolone

misoprostolmisoprostol

Drugs affecting gastric acid secretionDrugs affecting gastric acid secretion

• Muscarinic receptor antagonistsMuscarinic receptor antagonists


Pirenzepine Pirenzepine 哌仑西平哌仑西平

N

N

N

COCH 2 CH3

HO

N N---

1. Pharmacological effects and clinical uses1. Pharmacological effects and clinical uses• high affinity for M1- and low affinity for M2-receptors of the smooth mhigh affinity for M1- and low affinity for M2-receptors of the smooth muscle of the ileum and urinary bladder.uscle of the ileum and urinary bladder.• blocking of M1-muscarinic receptors in autonomic ganglia, inhibiting blocking of M1-muscarinic receptors in autonomic ganglia, inhibiting HCl secretionHCl secretion

2. Adverse effects2. Adverse effects• Atropine-like effects, especially at larger dosesAtropine-like effects, especially at larger doses

Other drugsOther drugs•TelenzepineTelenzepine （替仑西平）（替仑西平）•Atropine: atropine-like effectsAtropine: atropine-like effects•Propantheline bromide (Propantheline bromide ( 溴丙胺太林溴丙胺太林 ))


Sucralfate

carbonoxolone

misoprostol

• H2 receptor antagonists H2 receptor antagonists


Cimetidine Cimetidine 西咪替丁西咪替丁

NNN

CH2SCH2CH2NHCNHCH3

H

H3C

CN

ON CH2SCH2CH2NHCNHCH3

CHNO2

H3C

H3CCH2

cimetidinecimetidine

西咪替丁西咪替丁

ranitidineranitidine

雷尼替丁雷尼替丁

1. Pharmacological effects1. Pharmacological effects Blocking HBlocking H22 receptors, decreasing H receptors, decreasing H++ secretion secretion

2. Clinical uses2. Clinical uses• Duodenal and gastric ulcer, reflux esophagitis: relieving symptoDuodenal and gastric ulcer, reflux esophagitis: relieving sympto

ms, promoting healing of ulcers, and preventing ulcers ms, promoting healing of ulcers, and preventing ulcers • Zollinger-Ellison syndrome, acute stress ulcers, gastroesophageZollinger-Ellison syndrome, acute stress ulcers, gastroesophage

al reflux disease (heartburn)al reflux disease (heartburn)


Sucralfate

carbonoxolone

misoprostol

3. Adverse effects3. Adverse effects(1) Side effects: constipation, diarhoea, tiredness, muscular pain, etc.(1) Side effects: constipation, diarhoea, tiredness, muscular pain, etc.(2) CNS effects: headache, dizziness, confusion, hallucination, etc. (el(2) CNS effects: headache, dizziness, confusion, hallucination, etc. (el

derly, long-term uses)derly, long-term uses)(3) Endocretion effects: antiandrogen, gynecomastia ((3) Endocretion effects: antiandrogen, gynecomastia ( 男性乳房发育男性乳房发育 ), ),

galactorrhea (galactorrhea ( 溢乳溢乳 ), reduced sperm count, and male sexual dys), reduced sperm count, and male sexual dysfunctionfunction

4. Drug interactions4. Drug interactions• Inhibiting hepatic P450, raising plasma concentrations of warfaInhibiting hepatic P450, raising plasma concentrations of warfa

rin, phenytoin, diazepam, propranolol, quinidine and theophyllirin, phenytoin, diazepam, propranolol, quinidine and theophyllinene


Other agentsOther agents

Ranitidine Ranitidine 雷尼替丁雷尼替丁 • Longer acting; 4Longer acting; 4 ～～ 10 times more potent10 times more potent• Minimal side effects, on antiandrogenic and prolactin-stimMinimal side effects, on antiandrogenic and prolactin-stim

ulating effects, not inhibiting P450ulating effects, not inhibiting P450

Famotidine Famotidine 法莫替丁法莫替丁 • Similar to ranitidine, but 3Similar to ranitidine, but 3 ～～ 20 times more potent20 times more potent

Nizatidine Nizatidine 尼扎替丁尼扎替丁 • Bioavailability is near 100%, principally eliminated by kidnBioavailability is near 100%, principally eliminated by kidn

eyey


H+-K+-ATPase inhibitors( proton pump inhibitors )


Omeprazole Omeprazole 奥美拉唑奥美拉唑

N

OCH3H3C CH3

CH2

OCH3

S

O

H

N

N

1. Pharmacological effects1. Pharmacological effects(1) Inhibiting gastric acid secretion by various stimuli (histamine, g(1) Inhibiting gastric acid secretion by various stimuli (histamine, g

astrin, aspirin, ethanol, stress)astrin, aspirin, ethanol, stress)(2) Inhibiting H. pylori(2) Inhibiting H. pylori

2. Clinical uses2. Clinical uses(1) Highly effective for duodenal and gastric ulcer, reflux esophagit(1) Highly effective for duodenal and gastric ulcer, reflux esophagit

is: relieving symptoms, promoting healing of ulcersis: relieving symptoms, promoting healing of ulcers(2) Used with antimicrobial regimens to eradicate H. pylori (2) Used with antimicrobial regimens to eradicate H. pylori


Sucralfate

carbonoxolone

misoprostol

3. Adverse effects3. Adverse effects(1) Side effects:(1) Side effects: nausea, headache, diarrhoea, constipation and rash o nausea, headache, diarrhoea, constipation and rash occur but are uncommon ccur but are uncommon (2) Increase of gastric carcinoid tumor:(2) Increase of gastric carcinoid tumor: prolongated hypochlorhydria a prolongated hypochlorhydria and secondary hypergastrinemiand secondary hypergastrinemia(3) Other effects:(3) Other effects: gynecomastia ( gynecomastia ( 男性乳房发育男性乳房发育 ), hypersensitivity), hypersensitivity

4. Drug interactions4. Drug interactions•Inhibiting hepatic P450, raising plasma concentrations of warfarin, pInhibiting hepatic P450, raising plasma concentrations of warfarin, phenytoin, diazepam, etc.henytoin, diazepam, etc.


Other agentsOther agents

1.1. Lansoprazole Lansoprazole 兰索拉唑兰索拉唑

2.2. Pantoprazole Pantoprazole 泮他拉唑泮他拉唑

3.3. Rebeprazole Rebeprazole 雷贝拉唑雷贝拉唑


Mucosal protective drugsMucosal protective drugs

1.1. Misoprostol Misoprostol 米索前列醇米索前列醇2.2. Enprostil Enprostil 恩前列素恩前列素3.3. Sucralfate Sucralfate 硫糖铝硫糖铝4.4. Colloidal bismuth subcitrate Colloidal bismuth subcitrate 胶体次枸橼酸铋胶体次枸橼酸铋5.5. Teprenone Teprenone 替普瑞酮替普瑞酮6.6. Marzulene Marzulene 麦滋林麦滋林7.7. Smectite Smectite 思密达思密达8.8. Proglumide Proglumide 丙谷胺丙谷胺


Sucralfate

Bismuch, etc.

misoprostol


Misoprostol Misoprostol 米索前列醇米索前列醇

OHCH3OCH3

O O

HO


1. Pharmacological effects1. Pharmacological effects•Inhibiting gastric acid secretionInhibiting gastric acid secretion•Promoting mucus and HCO3Promoting mucus and HCO3- - secretion, and mucosal repairsecretion, and mucosal repair

2. Clinical uses2. Clinical uses•Ulcers, especially for NSAIDs-inducedUlcers, especially for NSAIDs-induced

3. Adverse effects3. Adverse effects•Side effects (13%): nausea, abdominal pain, diarrhea, headache, etc.Side effects (13%): nausea, abdominal pain, diarrhea, headache, etc.•Contraindicated in pregnancy womenContraindicated in pregnancy women


Antimicrobial drugs (for Helicobacter pylori)Antimicrobial drugs (for Helicobacter pylori)

1. Anti-ulcer drugs1. Anti-ulcer drugs• HH++-K-K++-ATPase inhibitors; bismuch ; sulralfate-ATPase inhibitors; bismuch ; sulralfate• Weaker, combined with antimicrobial drugsWeaker, combined with antimicrobial drugs

2. Antimicrobial drugs2. Antimicrobial drugs• metronidazole (metronidazole ( 甲硝唑甲硝唑 ); amoxicillin (); amoxicillin ( 阿莫西林阿莫西林 ););• tetracycline (tetracycline ( 四环素四环素 ); gentamicin (); gentamicin ( 庆大霉素庆大霉素 ); ); • clarithromycin (clarithromycin ( 克拉霉素克拉霉素 ))

•Helicobacter Helicobacter pylori in the pylori in the gastric mucosagastric mucosa

Sucralfate

Bismuch, etc.

misoprostol

B. Modulators of gastrointestinal functionsB. Modulators of gastrointestinal functions


1. Antiemetic and prokinetic drugs1. Antiemetic and prokinetic drugs• antiemetic drugsantiemetic drugs• prokinetic drugsprokinetic drugs2. Drugs for treatment of diarrhea 2. Drugs for treatment of diarrhea • antimotility drugsantimotility drugs• astringentsastringents• absorbantsabsorbants3. Laxatives3. Laxatives• contact (stimulant) laxativescontact (stimulant) laxatives• osmotic laxativesosmotic laxatives• faecal softners (emollients)faecal softners (emollients)


Antiemetic and prokinetic drugsAntiemetic and prokinetic drugs

Antiemetic drugsAntiemetic drugs

•H1 receptor antagonists:H1 receptor antagonists: diphenhydramine diphenhydramine 苯海拉明苯海拉明 ; dim; dimenhydrinate enhydrinate 茶苯海明茶苯海明 ; meclozine ; meclozine 美克洛嗪美克洛嗪•Muscarinic receptor antagonists:Muscarinic receptor antagonists: scopolamine scopolamine 东莨菪碱东莨菪碱•D2 receptor antagonists:D2 receptor antagonists: chlorpromazine chlorpromazine 氯丙嗪氯丙嗪•5-HT3 receptor antagonists5-HT3 receptor antagonists ：： ondansetron ondansetron 昂丹司琼昂丹司琼 ; grasetron ; grasetron 格拉司琼格拉司琼 ; tropisetron ; tropisetron 托烷司琼托烷司琼

孤束核孤束核


Ondansetron Ondansetron 昂丹司琼昂丹司琼

NN

NCH2

O

CH3

CH3


1. Pharmacological effects1. Pharmacological effects• Blocking 5-HTBlocking 5-HT33 receptor (central and peripheral) receptor (central and peripheral)

2. Clinical uses2. Clinical uses• Emesis induced by chemotherapy and radiotherapy in the Emesis induced by chemotherapy and radiotherapy in the patients with cancerspatients with cancers

3. Adverse effects3. Adverse effects• side effects: headache, constipation or diarrhea, etc. side effects: headache, constipation or diarrhea, etc.

孤束核孤束核

Antiemetic and prokinetic drugsAntiemetic and prokinetic drugs

Prokinetic drugsProkinetic drugs

Metoclopramide Metoclopramide 甲氧氯普胺甲氧氯普胺 (( 胃复安，灭吐灵胃复安，灭吐灵 ))

• DD22 receptor block: antiemetic effects (CTZ), promoting GI motility (GI) receptor block: antiemetic effects (CTZ), promoting GI motility (GI)• Adverse effects: CNS reactions, extrpyramidal effects, etc. Adverse effects: CNS reactions, extrpyramidal effects, etc.


Domperidone Domperidone 多潘立酮多潘立酮 (( 吗丁啉吗丁啉 ))

• DD22 receptor block: promoting GI motility (GI) receptor block: promoting GI motility (GI)• Adverse effects: headache, prolactin Adverse effects: headache, prolactin , gastric acid , gastric acid

Cisapride Cisapride 西沙必利西沙必利• ACh release ACh release : promoting intestinal and colon motility: promoting intestinal and colon motility


Action sites of prokinAction sites of prokinetic drugsetic drugs

GI tract smooth muscle cellsGI tract smooth muscle cells


Drugs for treatment of diarrhea Drugs for treatment of diarrhea

1.Antimotility drugs:1.Antimotility drugs: agonists for agonists for receptors in GI tract receptors in GI tract• opium preparationsopium preparations• diphenoxylate diphenoxylate 地芬诺酯（地芬诺酯（ CNS effects at larger doses)CNS effects at larger doses)• loperamine loperamine 洛哌丁胺洛哌丁胺 2.2. Astringents:Astringents:• tannalbin tannalbin 鞣酸蛋白鞣酸蛋白• bismuch subsalicylate; bismuch subcarbonate (bismuch subsalicylate; bismuch subcarbonate ( 铋制剂铋制剂 )) 3.3. AbsorbantsAbsorbants ：：• medical charchol medical charchol 药用炭（活性炭）药用炭（活性炭）• agysical agysical 矽炭银矽炭银


LaxativesLaxatives

1.Contact (stimulant) laxatives1.Contact (stimulant) laxatives• phenolphthalein phenolphthalein 酚酞酚酞• bisacodyl bisacodyl 必沙可啶必沙可啶• anthraquinones anthraquinones 蒽醌类（中药成分）蒽醌类（中药成分）2.Osmotic laxatives2.Osmotic laxatives• magnesium sulfate magnesium sulfate 硫酸镁硫酸镁 ; sodium sulfate ; sodium sulfate 硫酸钠；硫酸钠；• lactulose lactulose 乳果糖乳果糖 ; sorbitol ; sorbitol 山梨醇山梨醇 ; ; • glycerol glycerol 甘油甘油 ; celluloses ; celluloses 纤维素类纤维素类3.Faecal softners (emollients)3.Faecal softners (emollients)• liquid paraffin liquid paraffin 液体石蜡液体石蜡

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Gastrointestinal drugs 基础医学各论 II. Hepatic, pacreatic and biliary disordersHepatic, pacreatic and biliary disorders Ulcer disordersUlcer disorders Abnormal