gastrointestinal drugs department of pharmacology tang huifang ( 汤慧芳 )

Gastrointestinal drugsGastrointestinal drugs

Department of Pharmacology Department of Pharmacology Tang Huifang (Tang Huifang ( 汤慧芳汤慧芳 ))

Email: [email protected]: [email protected]

• Part 1. Drugs used for peptic ulcers• Part 2. Modulators of gastroenteric functions

Content

Pathogenesis of Pathogenesis of peptic ulcerspeptic ulcers• Infection with Infection with HpHp ;;• Increased gastric acid Increased gastric acid secretion;secretion;• Inadequate mucosal dInadequate mucosal defense to gastric acid.efense to gastric acid.

TreatmentTreatment approachesapproaches • Eradicating Eradicating HpHp ;;• Neutralizing gastric aNeutralizing gastric acid, cid, or or reducing secreducing secretion of the acid;retion of the acid;• ProtectingProtecting thethe gastric gastric mucosa from damage.mucosa from damage.

Peptic ulcers Peptic ulcers andand treatment treatmentPart 1. Part 1. Drugs used for peptic ulcersDrugs used for peptic ulcers

I. Antacids: neutralizing the acidI. Antacids: neutralizing the acidII. Drugs suppressing gastric acid secretionII. Drugs suppressing gastric acid secretion ①①Muscarinic receptor antagonistsMuscarinic receptor antagonists ② ②HH22 receptor antagonists receptor antagonists ③③Gastrin receptor antagonistsGastrin receptor antagonists ④ ④ HH++-K-K++-ATPase inhibitors (proton pump inhibitor-ATPase inhibitors (proton pump inhibitor

s)s)III. Antimicrobial drugs (III. Antimicrobial drugs (Helicobacter pyloriHelicobacter pylori))IV. Mucosal protective drugsIV. Mucosal protective drugs

Classifiction of anti-ulcer drugsClassifiction of anti-ulcer drugsDrugs used for peptic ulcersDrugs used for peptic ulcers

ⅠⅠ. Antacids(. Antacids( 抗酸药抗酸药 )) • Basic substances that can reduce gastric aciditBasic substances that can reduce gastric acidity by neutralizing HCl;y by neutralizing HCl;• Drugs most in use:Drugs most in use: Aluminium hydroxide(Aluminium hydroxide( 氢氧化铝氢氧化铝 ),), Magnesium hydroxide(Magnesium hydroxide( 氢氧化镁氢氧化镁 ),), Magnesium trisilicate(Magnesium trisilicate( 三硅酸镁三硅酸镁 ),), Magnesium oxide(Magnesium oxide( 氧化镁氧化镁 ), ), etc.etc. Composition resparation,Composition resparation, such as:such as: Tab aluminium hydroxide compound(Tab aluminium hydroxide compound( 复方氢氧复方氢氧化铝片化铝片 , , 胃舒平胃舒平 ), ), etc.etc.

Drugs used for peptic ulcersDrugs used for peptic ulcers

(1) Antacids(1) Antacids1. 1. Pharmacological effectPharmacological effect Neutralizing gastric acid, diminish gastric acidity and iNeutralizing gastric acid, diminish gastric acidity and inactivate pepsinnactivate pepsin （胃蛋白酶）（胃蛋白酶） activityactivity 2. 2. Clinical usesClinical uses UUsed for peptic ulcer and acid-hypersecretory conditised for peptic ulcer and acid-hypersecretory conditionsons..


3. 3. Adverse effectsAdverse effects(1) Constipation and stomach cramp (salt of aluminum) (2) Diarrhea (salt of magnesium)(3) Hypercalcium which can cause renal failure (Calcium)(4) Hypernatremia (sodium-containing antacids)4.4. Drug interactions Drug interactions Avoid concurrent administration of antacids and a varAvoid concurrent administration of antacids and a variety of drugs .iety of drugs .(1) Affect rates of dissolution and absorption, bioavail(1) Affect rates of dissolution and absorption, bioavailbility, and renal elimination of many drugsbility, and renal elimination of many drugs(2) By binding to drugs (for example, tetracycline(2) By binding to drugs (for example, tetracycline 四环四环素素 ), form insoluble complexes that are not absorbed), form insoluble complexes that are not absorbed


Adminstration and dosage

(1) Take antacids 1 h and 3 h after meals Seven times a day after meals and at bedtime. (2) Should not be taken continuously for more than 3 m for ulcer (3) To help avoid or reduce drug interaction, other medication should not be taken within 1-2 hours of taking an antacids


ⅡⅡ. . Drugs inhibiting gastric acid secretionDrugs inhibiting gastric acid secretionDrugs used for peptic ulcersDrugs used for peptic ulcers

①①Muscarinic receptor antagonistsMuscarinic receptor antagonists②②HH22 receptor antagonists receptor antagonists③③Gastrin receptor antagonistsGastrin receptor antagonists④④ HH++-K-K++-ATPase inhibitors (proton pump inhi-ATPase inhibitors (proton pump inhibitors)bitors)

Sucralfatecarbonoxolone

misoprostol

atropine

atropine

A.A. Muscarinic receptor antagonists Muscarinic receptor antagonists (M receptor blocker):(M receptor blocker):Drugs most in use:Drugs most in use: Atropine(Atropine( 阿托品阿托品 )) Propantheline bromidePropantheline bromide(( 溴丙胺太溴丙胺太林林 )) Pirenzepine(Pirenzepine( 哌仑西平哌仑西平 ) ) TelenzepineTelenzepine(( 替仑西平替仑西平 ))


OH

CH

NCH3

CH

CH3

CH3

CH O CH C6H5

CH2CH2

CH2

C

O

Atropine(Atropine( 阿托品阿托品 ))

Non-selective M receptor blocker:Non-selective M receptor blocker: Block MBlock M11, M, M22, M, M33, M, M44, and M, and M55 receptor receptors.s. Block M3 receptor in Parietal cells( 壁细胞 )Block M1 receptor in ganglionBlock M receptors in ECL and G cells.

Pirenzepine(Pirenzepine( 哌仑西平哌仑西平 ))

N

N

N

COCH2 CH3

HO

N N---


Selective M receptor blocker:Selective M receptor blocker: Only block MOnly block M11 and M and M22-receptors. -receptors.


misoprostol

1. Pharmacological effects1. Pharmacological effects high affinity for Mhigh affinity for M11- and low affinity for M- and low affinity for M22-receptors of the smooth muscle of the ile-receptors of the smooth muscle of the ileum and urinary bladder.um and urinary bladder. blocking of Mblocking of M11-muscarinic receptors in a-muscarinic receptors in autonomicutonomic ganglia,ganglia, inhibitinginhibiting thethe secretion osecretion of HCl.f HCl.2. Clinical uses:2. Clinical uses: peptic ulcerspeptic ulcers3. Adverse effects3. Adverse effects Atropine-like effects, at larger doses.Atropine-like effects, at larger doses.


TelenzepineTelenzepine(( 替仑西平替仑西平 ))

B.B. H H2 2 receptor antagonists:receptor antagonists: NN

N

CH2SCH2CH2NHCNHCH3

HH3C

CN

ON CH2SCH2CH2NHCNHCH3

CHNO2

H3C

H3CCH2

CimetidineCimetidine(( 西咪替丁西咪替丁 ))RanitidineRanitidine(( 雷尼替雷尼替丁丁 ))



misoprostol

Cimetidine(Cimetidine( 西咪替丁西咪替丁 ))1. Pharmacological effects1. Pharmacological effects Blocking HBlocking H2 2 receptors, decreasing Hreceptors, decreasing H++ secr secretionetion2. Clinical uses2. Clinical uses (1) Duodenal and gastric ulcer:(1) Duodenal and gastric ulcer: —— —— relieving symptoms, promoting herelieving symptoms, promoting healing of ulcers, and preventing ulcers.aling of ulcers, and preventing ulcers. (2) (2) Zollinger-Ellison syndromeZollinger-Ellison syndrome (3) Reflux esophagitis;(3) Reflux esophagitis; (4) Acute stress ulcers, etc.(4) Acute stress ulcers, etc.


3. Adverse effects3. Adverse effects (1)Side effects:(1)Side effects: constipation, diarhoea, ticonstipation, diarhoea, tiredness, muscular pain, etc.redness, muscular pain, etc. (2)CNS effects:(2)CNS effects: headache, dizziness, hal-luheadache, dizziness, hal-lucination, etc. (elderly, long-term uses)cination, etc. (elderly, long-term uses) (3)Endocretion effects:(3)Endocretion effects: antiandrogen,antiandrogen, gynecomastia(gynecomastia( 男性乳房发育男性乳房发育 ), galactorrh-), galactorrh-ea(ea( 溢乳溢乳 ), reduced sperm count, and mal), reduced sperm count, and male sexual dysfunctione sexual dysfunction4. Drug interactions4. Drug interactions Inhibiting hepatic PInhibiting hepatic P450450:: raising plasma craising plasma concentrations ofoncentrations of warfarin, phenytoin, dwarfarin, phenytoin, diazepam, propranolol, quinidine iazepam, propranolol, quinidine and and ththeophylline, eophylline, etc.etc.


5. Elimination Urinary excretion is the principal route of elimination of cimetidine, the dose should be modified in patients with renal impairment.


Other HOther H2 2 receptor antagonists:receptor antagonists:Ranitidine(Ranitidine( 雷尼替丁雷尼替丁 )) Similar to Similar to cimetidinecimetidine,, but 5 but 5 ～～ 10 times more potent, lon10 times more potent, longer acting;ger acting; Minimal side effects, no antiandrogenic and prolactin-Minimal side effects, no antiandrogenic and prolactin-stimulating effects, less inhibiting Pstimulating effects, less inhibiting P450450..Famotidine(Famotidine( 法莫替丁法莫替丁 )) Similar to Similar to ranitidineranitidine,, but 4 but 4 ～～ 8 times more potent.8 times more potent.Nizatidine(Nizatidine( 尼扎替丁尼扎替丁 )) The potent is similar to The potent is similar to ranitidine.ranitidine. Bioavailability is near 100%, principally eliminated by kiBioavailability is near 100%, principally eliminated by kidneydney


Drugs used for peptic ulcersDrugs used for peptic ulcers4 4 种种 HH22-- 受体阻断药的比较受体阻断药的比较

西咪替丁西咪替丁 2 12 1 400mg, bid 400mg, bid 11雷尼替丁雷尼替丁 2-32-3 5-105-10 150mg, bid 150mg, bid 0.10.1法莫替丁法莫替丁 2.5-4 402.5-4 40 20mg, bid 20mg, bid 00尼扎替丁尼扎替丁 2 5-102 5-10 150mg, bid 150mg, bid 00

药药名名 tt1/21/2(h)(h) 相对抑相对抑酸活力酸活力剂　量剂　量对肝药对肝药酶抑制酶抑制

C.C. H H++-K-K++-ATPase inhibitors-ATPase inhibitors (proton pump inhibitors)(proton pump inhibitors)Omeprazole(Omeprazole( 奥美拉唑奥美拉唑 ))

N

OCH3H3C CH3

CH2

OCH3

S

O

H

N

N


Omepranzole×

(the proton pump)


质子泵的分子构型质子泵的分子构型


1. Pharmacological effects1. Pharmacological effects (1)Inhibiting gastric acid secretion by various sti(1)Inhibiting gastric acid secretion by various stimulimuli(such as: histamine, gastrin, (such as: histamine, gastrin, aspirin, aspirin, ethethanol, stress, anol, stress, etc.etc.)) (2)Inhibiting (2)Inhibiting HpHp ..((3) protection for gastric mucosa3) protection for gastric mucosa2. Clinical uses2. Clinical uses (1)Highly effective for duodenal and gas-tric ulce(1)Highly effective for duodenal and gas-tric ulcer:r: relieving symptoms, andrelieving symptoms, and promoting healing of ulcerspromoting healing of ulcers Used with antimicrobial agents to eradicate Used with antimicrobial agents to eradicate HpHp .. (2)Reflux esophagitis;(2)Reflux esophagitis; (3)Zollinger-Ellison syndrome(3)Zollinger-Ellison syndrome


3. Adverse effects3. Adverse effects (1)Side effects:(1)Side effects: Less,Less, such as: such as: nausea, headache, diarrhoea, nausea, headache, diarrhoea, constipation and rash occur. constipation and rash occur. (2)Increase of gastric carcinoid tumor(2)Increase of gastric carcinoid tumor (3)Others: (3)Others: hypersensitivity, gynecomastiahypersensitivity, gynecomastia(( 男性乳房发男性乳房发育育 ))4.4. Drug interactionsDrug interactions Inhibiting hepatic P450,Inhibiting hepatic P450, raising plasma conceraising plasma concentrations ofntrations of warfarin, phenytoin, diazepam,warfarin, phenytoin, diazepam, etetc.c.


OthersOthers• Lansoprazole(Lansoprazole( 兰索拉唑兰索拉唑 ))• Pantoprazole(Pantoprazole( 泮他拉唑泮他拉唑 ))• Rebeprazole(Rebeprazole( 雷贝拉唑雷贝拉唑 ))


tt1/21/2 有效抑酸有效抑酸剂量剂量对肝药对肝药 (h)(h) 时间时间 (h)(h) (mg/d)(mg/d) 酶影响酶影响奥美拉唑奥美拉唑 1.01.0 1212 ～～ 2424 2020 ～～ 4040 + +兰索拉唑兰索拉唑 1.51.5 2424 3030 潘托拉唑潘托拉唑 1.31.3 2424 2020 ～～ 4040 雷贝拉唑雷贝拉唑 1.01.0 2424 2020

几几种质子泵抑制剂的比较种质子泵抑制剂的比较药　名药　名


丙谷胺丙谷胺 ((Proglumide)Proglumide)　　　　本品可与本品可与胃泌素胃泌素竞争受体而抑制胃酸分泌竞争受体而抑制胃酸分泌 ; ; 也能促进黏液合成也能促进黏液合成 , , 增强胃黏膜的黏液增强胃黏膜的黏液 --HCOHCO33

-- 盐屏障盐屏障 , , 从而发挥抗溃疡病的作用从而发挥抗溃疡病的作用 .. 本品口服吸收迅速本品口服吸收迅速 , , 生物利用度为生物利用度为 6060%% ～～ 74%, 74%, 达峰时间为达峰时间为 2h.2h.

胃泌素受体阻断药胃泌素受体阻断药 ::

ⅢⅢ. Mucosal protective drugs. Mucosal protective drugs Misoprostol(Misoprostol( 米索前列醇米索前列醇 )) Enprostil Enprostil 恩前列素恩前列素 Sucralfate Sucralfate 硫糖铝硫糖铝 Colloidal bismuth subcitrate(CBS, Colloidal bismuth subcitrate(CBS, 胶体次枸橼胶体次枸橼酸铋酸铋 )) Teprenone(Teprenone( 替普瑞酮替普瑞酮 )) Marzulene(Marzulene( 麦滋林麦滋林 )) Smectite(Smectite( 思密达思密达 ))


SucralfateBismuch, etc.

misoprostol

OHCH3OCH3

O O

HO

MisoprostolMisoprostol 米索前列醇米索前列醇

A prostaglandin E analogues


MisoprostolMisoprostol 米索前列醇米索前列醇1. 1. Pharmacological effectsPharmacological effectsInhibiting gastric acid secretionInhibiting gastric acid secretionPromoting mucus and HCOPromoting mucus and HCO33-- secretion, and mucosal repair secretion, and mucosal repair2. 2. Clinical usesClinical usesOnly approved for the prevention of NSAIDs-induced gastric Ulcer.Only approved for the prevention of NSAIDs-induced gastric Ulcer.3. 3. Adverse effectsAdverse effectsSide effects (13%):abdominal pain, diarrhea, nausea, headache, Side effects (13%):abdominal pain, diarrhea, nausea, headache, etc.etc.Contraindicated in pregnancy womenContraindicated in pregnancy women (Abortifacient (Abortifacient 堕胎堕胎 property)property)


Sucralfate

A sulfated disaccharide （二糖） complex of aluminum hydroxide


Sucralfate1. 1. Pharmacological effectsPharmacological effects1) Binding to mucosal surface and forms a protective barrier2) Enhancing cell restitution and re-epithelization.3) Weakly inhibiting H.Pylory growth.4) Promote PGE2 production5) Binding to pepsin and then reduce its activity2. 2. Clinical uses and AdminstrationClinical uses and Adminstration peptic ulcers, but with the advent of more effective agents (proton pump inhibitors); reflux esophagitis; mucosa impairment. Take sucralfate 1 hour before meals Four times a day before meals and at bedtime3. 3. Adverse effectsAdverse effectsConstipation occurs in 2% due to the aluminum salt, not together with alkaline agents


Bismuth CompoundsColloidal bismuth subcitrate (CBS, 胶体次枸橼酸铋 )Bismuth subslicylate

1. 1. Pharmacological effectsPharmacological effects1) Probably coats ulcers and erosions, creating a protective layer against acid and pepsin2) Inhibit pepsin activity, stimulate prostaglandin, mucus, and bicarbonate secretion3) Have direct antimicrobial activity against H pylori


2. 2. Clinical usesClinical uses1) Treatment of dyspepsia, peptic ulcer, chronic gastritis.2) Used in multidrug regimens for the eradication of H pylori infection.3. 3. Adverse effectsAdverse effects Causes blackening of the stool, which may be confused with gastrointestinal bleeding Bismuth toxicity resulting in encephalopathy (ataxia, headaches, confusion, seizures).

Bismuth CompoundsDrugs used for peptic ulcersDrugs used for peptic ulcers

Smectite( 蒙脱石 )1) Bind to the glycoprotein in the mucus to increase its coverage ability, enhancing cell restitution, antimicrobial activity against H pylori. 2) Use for acute or chronic diarrhea and ulcer.


ⅣⅣ. Antimicrobial. Antimicrobial(anti-(anti-HpHp)) drugs drugs1. Anti-ulcer drugs:1. Anti-ulcer drugs: HH++-K-K++-ATPase inhibitors; bismuch(-ATPase inhibitors; bismuch( 铋剂铋剂 );); sulralfate( sulralfate( 硫糖铝硫糖铝 ), ), etc.etc. Weaker, combined with antimicrobial dWeaker, combined with antimicrobial drugs.rugs.2. Antimicrobial drugs:2. Antimicrobial drugs: Metronidazole(Metronidazole( 甲硝唑甲硝唑 ); Amoxicillin(); Amoxicillin( 阿阿莫西林莫西林 ); 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 ), ), etc.etc.


SucralfateBismuch, etc.

misoprostol

HP 根除治疗方案的变化• -- 第四次全国幽门螺杆菌感染处理共识报告（ 2012 年）• 我国 HP感染率总体上仍然很高，成人感染率在 40-60% 。• 推荐用于根除治疗的 6种抗菌药物中，甲硝唑耐药率已达到 60%-70% ，克拉霉素达 20%--38% ，左氧氟沙星达到 30%--38% ，耐药显著影响根除率。• 羟氨苄青霉素、呋喃唑酮和四环素的耐药率仍很低（ 1%-5% ）。• 因此标准三联疗法（ PPI+ 克拉霉素 +羟氨苄 ) 或（ PPI+ 克拉霉素 +甲硝唑）根除率已低于或远低于 80% 。• 共识：推荐四联： PPI+ 铋剂 +2种抗菌药物• 抗菌药物组成：

– 羟氨苄青霉素 +克拉霉素– 羟氨苄青霉素 +左氧氟沙星– 羟氨苄青霉素 +呋喃唑酮– 四环素 +甲哨唑或呋喃唑酮

新进展新进展

• 青霉素过敏者推荐的抗菌药物组成方案：– 克拉霉素 +左氧氟沙星– 克拉霉素 +呋喃唑酮– 四环素 +甲硝唑或呋喃唑酮– 克拉霉素 +甲硝唑

• 疗程： 10d--14d ，放弃 7d 方案。

新进展新进展

Gastrointestinal drugsPart2 Part2 Modulators of gastrointestinal functionsModulators of gastrointestinal functions

Abnormalities of gastrointestinal functionsAbnormalities of gastrointestinal functions

Nausea and vomiting ConstipationDiarrhea

Modulators of gastrointestinal functionsModulators of gastrointestinal functions

ContentsContentsⅠⅠ. Promoting digestive drug. Promoting digestive drug(( 助消化助消化

药药 ))ⅡⅡ. Antiemetic and prokinetic drugs. Antiemetic and prokinetic drugs 1.1. antiemetic drugs(antiemetic drugs( 止吐药止吐药 )) 2. prokinetic drugs(2. prokinetic drugs( 胃动力药胃动力药 ))ⅢⅢ. Drugs for treatment of diarrhea . Drugs for treatment of diarrhea 1. antimotility drugs(1. antimotility drugs( 抗蠕动药抗蠕动药 )) 2. astringents(2. astringents( 收敛药收敛药 )) 3. absorbants(3. absorbants( 吸附药吸附药 ))ⅣⅣ. Laxatives. Laxatives 1. contact(stimulant) laxatives1. contact(stimulant) laxatives 2. osmotic laxatives2. osmotic laxatives 3. faecal softners(emollients)3. faecal softners(emollients)

ⅠⅠ.. Promoting digestive drugPromoting digestive drug Pepsin(Pepsin( 胃蛋白酶胃蛋白酶 )) Pancreatin(Pancreatin(胰酶胰酶 )) Lactasin(Lactasin( 乳酶生乳酶生 , Biofermin, , Biofermin, 表飞表飞鸣鸣 ) ) etc.etc.


ⅡⅡ.. Antiemetic and prokinetic drugsAntiemetic and prokinetic drugs 1. Antiemetic drugs(1. Antiemetic drugs( 止吐药止吐药 )) HH11 receptor antagonists(H receptor antagonists(H11 受体阻断药受体阻断药 ): ): DiphenhydramineDiphenhydramine((苯海拉明苯海拉明 );); Dimenhydrinate(Dimenhydrinate( 茶苯海明茶苯海明 );); Meclozine(Meclozine( 美克洛嗪美克洛嗪 )) M receptor antagonists(MM receptor antagonists(M 受体阻断药受体阻断药 ):): ScopolamineScopolamine(( 东莨菪碱东莨菪碱 )) DD22 receptor antagonists(D receptor antagonists(D22 受体阻断药受体阻断药 ):): ChlorpromazineChlorpromazine(( 氯丙嗪氯丙嗪 )) 5-HT5-HT33 receptor antagonists(5-HT receptor antagonists(5-HT33 受体阻断药受体阻断药 ):): 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 ))


2. Prokinetic drugs(2. Prokinetic drugs( 胃动力药胃动力药 )) Metoclopramide(Metoclopramide( 甲氧氯普胺甲氧氯普胺 , , 胃复安胃复安 , , 灭吐灭吐灵灵 )) DD22 receptor block: antiemetic effects(CTZ), an receptor block: antiemetic effects(CTZ), and promoting GI motility.d promoting GI motility. Adverse effects: CNS reactions, extrapyra-miAdverse effects: CNS reactions, extrapyra-midal effects, dal effects, etc.etc. Domperidone(Domperidone( 多潘立酮多潘立酮 , , 吗丁啉吗丁啉 )) DD22 receptor block: promoting GI motility. receptor block: promoting GI motility. Adverse effects: headache, prolactin Adverse effects: headache, prolactin , gastri, gastric acid c acid Cisapride(Cisapride( 西沙比利西沙比利 )) 5-HT4 receptor activitor, 5-HT4 receptor activitor, ACh releaseACh release : promo: promoting intestinal & colon motility.ting intestinal & colon motility.


GI tract smooth muscle cellsGI tract smooth muscle cells

NANCneuron

Cholinergic neuronPost-ganglionic primary motor neuron

Prokinetic drugsProkinetic drugs

Prokinetic drugsProkinetic drugsMetoclopramide Metoclopramide 甲氧氯普胺甲氧氯普胺

Mechanism of action

1) Block D2 receptor, to stimulate 5-HT4 receptors and enhance coordinated transmission in cholinergic nerve plexues2) An dopaminergic neuron antagonist in the central nervous system; at higher doses, 5-HT3 antagonist activity may also contribute to the anti-emetic effect. Clinical usesClinical uses1) Used for treatment of diabetic gastroparesis2) Used for the prevention of nausea and vomiting associated with cancer chemotherapy or occurring post-operatively.


Adverse effectsAdverse effects 1) Fatigue, dizziness, faintness 2) Various extrapyramidal syndromes caused by its central anti-dopaminergic activity. Parkinsonism (reversible) tardive dyskinesia (irreversible) 3) Increased serum prolactin levels (chronic uses)

MetoclopramidMetoclopramideeModulators of gastrointestinal functionsModulators of gastrointestinal functions

Domperidone Domperidone 多潘立酮多潘立酮 Mechanism of action A peripherial dopamine antagonist, has no procholinergi

cEffectsClinical usesClinical uses 1) Used for treatment of diabetic gastroparesis 2) Used for the prevention of nausea and vomiting induced by dyspepsia, chemotherapy, gastroesophageal regastroesophageal reflux diseaseflux disease .Adverse effectsAdverse effectsHas few side effects because it can not cross the BBBHas few side effects because it can not cross the BBBIncreased serum prolactin levels (6% of patients)Rare cases of prolongation of QT interval.


ⅢⅢ. Drugs for treatment of diarrhea. Drugs for treatment of diarrhea(( 止泻药止泻药 ) ) 1.1. Antimotility drugsAntimotility drugs(( 抗蠕动药抗蠕动药 )) : : agonists for agonists for receptors in GI tract receptors in GI tract Opium preparations(Opium preparations( 阿片制剂阿片制剂 )) Diphenoxylate(Diphenoxylate(地芬诺酯地芬诺酯 ): ): CNS effects at larger doses.CNS effects at larger doses.2.2. AstringentsAstringents(( 收敛药收敛药 )) : : Tannalbin(Tannalbin(鞣酸蛋白鞣酸蛋白 )) Bismuch subsalicylate(Bismuch subsalicylate( 次硅酸铋次硅酸铋 )) Bismuch subcarbonate(Bismuch subcarbonate( 次碳酸铋次碳酸铋 )) 3. Absorbants3. Absorbants(( 吸附药吸附药 )) : : Medical charchol(Medical charchol( 药用炭药用炭 , , 活性炭活性炭 )) Agysical(Agysical(矽炭银矽炭银 ))


1. Antimotility drugs: 1. Antimotility drugs: Mechanisms: Mechanisms: Agonists for Agonists for receptors in receptors in GI tractGI tract (1) Opium preparation (1) Opium preparation 阿片制剂阿片制剂 (2)(2) Diphenoxylate Diphenoxylate 地芬诺酯地芬诺酯Diphenoxylate Diphenoxylate dose not cross the blood-brain-barrierdose not cross the blood-brain-barrier as as easly as most opioids do and is relatively selective for peeasly as most opioids do and is relatively selective for peripheral opioid receptors. Hasripheral opioid receptors. Has CNS effects at larger dose CNS effects at larger doses)s)

Anti-diarrhealsAnti-diarrhealsModulators of gastrointestinal functionsModulators of gastrointestinal functions

Anti-diarrhealsAnti-diarrheals1. Antimotility drugs:1. Antimotility drugs:

Loperamide Loperamide 洛哌丁胺洛哌丁胺It is two to three times potent than diphenoxylate, It is two to three times potent than diphenoxylate, and its action is more rapid in onset and more proland its action is more rapid in onset and more prolonged. onged. Use for acute or chronic diarrhea but not induced bUse for acute or chronic diarrhea but not induced by infection.y infection.It has less CNS or cardiovascular effectsIt has less CNS or cardiovascular effects .


ⅣⅣ. Laxatives(. Laxatives(泻药泻药 ))1. Stimulant laxatives(1. Stimulant laxatives( 刺激性泻药刺激性泻药 )) Phenolphthalein(Phenolphthalein(酚酞酚酞 )) Bisacodyl(Bisacodyl(必沙可啶必沙可啶 )) Rhubarb(Rhubarb( 大黄大黄 )) 、、 Senna(Senna(番泻叶番泻叶 ), etc.), etc.2. Osmotic laxatives(2. Osmotic laxatives( 渗透性泻药渗透性泻药 )) 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(3. Faecal softners( 粪便软化药粪便软化药 , emollients), emollients) Liquid paraffin(Liquid paraffin( 液体石蜡液体石蜡 ))


LaxativesLaxatives• 1. Stimulant laxatives(1. Stimulant laxatives(刺激性泻药刺激性泻药 )) Phenolphthalein Phenolphthalein 酚酞酚酞 ( No longer used because of concerns about carcigeni( No longer used because of concerns about carcigeni

city)city) Bisacodyl Bisacodyl 必沙可啶必沙可啶 (It is active after deacetylation, stimulating enteric n(It is active after deacetylation, stimulating enteric n

erves to cause colonic mass movements; increases flerves to cause colonic mass movements; increases fluid and NaCl secretion. )uid and NaCl secretion. )


LaxativesLaxativesAnthraquinones Anthraquinones 蒽醌类（中药成分）蒽醌类（中药成分）

promote colon movementspromote colon movements

Cascara（鼠李皮） Rhubarb （大黄） Senna （番泻叶）


2. Osmotic laxatives(2. Osmotic laxatives( 渗透性泻药渗透性泻药 )) 1) Salt laxatives: magnesium sulfate 1) Salt laxatives: magnesium sulfate 硫酸镁硫酸镁 ; sodium sulfate ; sodium sulfate 硫酸钠；硫酸钠；

LaxativesLaxatives

These agents contain ions that are only slowly absorbed from the intestine. These ions retain fluid in the bowel lumen and cause a large volume of fluid to enter the colon.

magnesium sulfatemagnesium sulfate


2. 2. Osmotic laxatives(渗透性泻药 ) 2) Lactulose 2) Lactulose 乳果糖乳果糖 ; ;

LaxativesLaxatives

In the small bowel, it is resistant to hydrolysis and has an osmotic effect.In the large intestine, lactulose is acted upon by the endogenous flora with the production of lactic acid, Lactic acid also has an osmotic effect. It is used to reduce ammonia blood levels in the prevention and treatment of hepatic encephalopathy


3. Laxatives that decrease absorption3. Laxatives that decrease absorptionLiquid petrolatum( Lubricate the fecal mass, prevent excessive dehydration of the material , and may inhibit water reabsorption by coating the gut wall)


gastrointestinal drugs department of pharmacology tang huifang ( 汤慧芳 )

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