Gastrointestinal drugs. Part 1. Drugs used for peptic ulcers Part 2. Modulators of gastroenteric...

GastrointestinaGastrointestinal drugsl drugs

Part 1. Drugs used for peptic ulcers

Part 2. Modulators of gastroenteric functions

Content

Part 1. Part 1. Drugs used for peptic ulcersDrugs used for peptic ulcers

The The Pathogenesis of peptic Pathogenesis of peptic ulcersulcers::

1. Infection with1. Infection with Helicobacter Helicobacter pylori pylori ((HpHp););

2. Increased gastric acid 2. Increased gastric acid secretion; secretion;

3. Inadequate mucosal defense 3. Inadequate mucosal defense to gastric acid.to gastric acid.

Drugs used for peptic Drugs used for peptic ulcersulcers

InfectionInfection

▲ ▲ Infection withInfection with HpHp and peptic and peptic ulcers:ulcers:


InflammationInflammation


UlcersUlcers


巴里巴里 ··马歇尔马歇尔与与罗宾罗宾 ··沃伦沃伦的这一研究成果获得的这一研究成果获得 20052005 年诺贝尔年诺贝尔生理学或医学奖生理学或医学奖 . 10. 10 月月 33 日日 , , 正在工作聚会的两位澳大利亚科正在工作聚会的两位澳大利亚科学家得知自己获得学家得知自己获得 20052005 年诺贝尔生理学或医学奖后举杯互相年诺贝尔生理学或医学奖后举杯互相庆贺庆贺 ..

罗宾罗宾 ·· 沃伦沃伦巴里巴里 ·· 马歇尔马歇尔

▲▲ Increased Gastric acid Gastric acid secretionsecretion无酸，便无溃疡—— 1910

年， Schiwatz


Basolateral membane

(the proton pump)

Mucus-bicarbonate barrier

▲▲ Inadequate mucosal defense Inadequate mucosal defense to gastric acid.to gastric acid.



Pathogenesis of Pathogenesis of peptic ulcerspeptic ulcers

• Infection with Infection with HpHp ;;• Increased gastric Increased gastric

acid secretion;acid secretion;

• Inadequate Inadequate mucosal defense mucosal defense to gastric acid.to gastric acid.

TreatmentTreatment approachesapproaches

• Eradicating Eradicating HpHp ;;• Neutralizing Neutralizing

gastric acid, gastric acid, or or reducing secretion reducing secretion of the acid;of the acid;

• ProtectingProtecting thethe gastric mucosa gastric mucosa from damage.from damage.

Peptic ulcers Peptic ulcers andand treatmenttreatment

I.I. Antacids: neutralizing the acidAntacids: neutralizing the acid

II. 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 -ATPase inhibitors (proton pump

inhibitors)inhibitors)

III. Antimicrobial drugs (III. Antimicrobial drugs (Helicobacter pyloriHelicobacter pylori))

IV. Mucosal protective drugsIV. Mucosal protective drugs

Classifiction of anti-ulcer Classifiction of anti-ulcer drugsdrugs


ⅠⅠ. Antacids(. Antacids( 抗酸药抗酸药 )) Basic substances that can reduce gastric Basic substances that can reduce gastric

acidity by neutralizing HCl;acidity 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:

复方氢氧化铝片（复方氢氧化铝片（胃舒平胃舒平 ),), 铝碳酸镁咀嚼片（达喜）铝碳酸镁咀嚼片（达喜）


Sucralfatecarbonoxolone

misoprostol


(1) Antacids(1) Antacids1. 1. Pharmacological effectPharmacological effect

Neutralizing gastric acid, diminish gastric Neutralizing gastric acid, diminish gastric

acidity and inactivate pepsinacidity and inactivate pepsin （胃蛋白酶）（胃蛋白酶） activityactivity

2. 2. Clinical usesClinical uses

UUsed for peptic ulcer and acid-hypersecretory sed for peptic ulcer and acid-hypersecretory

conditionsconditions..


3. 3. Adverse effectsAdverse effects(1) Constipation and stomach cramp (salt of aluminum ，松弛平滑肌 ) (2) Diarrhea (salt of magnesium)(3) Hypercalcium which can cause renal failure (Calcium)(4) Hypernatremia (sodium-containing antacids)


Adminstration and dosage

(1) Take antacids 1 h and 3 h after

meals

(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 Drugs inhibiting gastric acid secretionsecretion


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(( 溴丙胺太林溴丙胺太林 )) Pirenzepine(Pirenzepine( 哌仑西平哌仑西平 ) ) TelenzepineTelenzepine(( 替仑西平替仑西平 ))


B. 4 B. 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, 150mg, bid 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

主要区别：药动学和引起药物相互作用的特性

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

Omeprazole(Omeprazole( 奥美拉奥美拉唑唑 ))

N

OCH3H3C CH3

CH2

OCH3

S

O

H

N

N


Omepranzole

×

(the proton pump)


1. Pharmacological effects1. Pharmacological effects

(1)Inhibiting gastric acid secretion by (1)Inhibiting gastric acid secretion by

various stimuli(such as: histamine, various stimuli(such as: histamine,

gastrin, aspirin, ethanol, stress, gastrin, aspirin, ethanol, stress, etc.etc.))

(2)Inhibiting (2)Inhibiting HpHp ..

(3) protection for gastric mucosa(3) protection for gastric mucosa


2. Clinical uses2. Clinical uses

(1)Highly effective for duodenal and (1)Highly effective for duodenal and

gas-tric ulcer: relieving symptoms, gas-tric ulcer: relieving symptoms,

andand

promoting healing of ulcerspromoting healing of ulcers

Used with antimicrobial agents to Used with antimicrobial agents to

eradicate eradicate Hp .Hp .

(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:

nausea, headache, diarrhoea, constipation and rash nausea, headache, diarrhoea, constipation and rash

occur. occur.

(2)Others: (2)Others:

gynecomastiagynecomastia(( 男性乳房发育男性乳房发育 ))

4.4. Drug interactionsDrug interactions

Inhibiting hepatic P450,Inhibiting hepatic P450, raising plasma raising plasma

concentrations ofconcentrations of warfarin, phenytoin, diazepam,warfarin, phenytoin, diazepam,

etc.etc.


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对肝药肝药 (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


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, 胶体次胶体次

枸橼酸铋枸橼酸铋 ))

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 ))

Proglumide(Proglumide( 丙谷胺丙谷胺 ) )


SucralfateBismuch, etc.

misoprostol

OHCH3OCH3

O O

HO

(3) Mucosal protective drugs(3) Mucosal protective drugs

MisoprostolMisoprostol 米索前列醇米索前列醇

A prostaglandin E analogues


Misoprostol 米索前列醇

1. Pharmacological effectsInhibiting gastric acid secretionPromoting mucus and HCO3

- secretion, and mucosal repair

2. Clinical usesOnly approved for the prevention of NSAIDs-

induced gastric Ulcer.3. Adverse effectsSide effects (13%):abdominal pain, nausea,

headache, etc.Contraindicated in pregnancy women (Abortifacient 堕胎 property)



Sucralfate

硫酸蔗糖和氢氧化铝构成。 PH<4 ，交联，聚合成有黏性的胶状聚合物，粘附于上皮细胞和基底膜达 6 个小时。


Sucralfate

1. 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 activity

2. 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.




Bismuth Compounds

Colloidal 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 （消化不良） , 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).

Bismuth Compounds


ⅣⅣ. Antimicrobial. Antimicrobial(anti-(anti-HpHp)) drugsdrugs

1. Anti-ulcer drugs:1. Anti-ulcer drugs: HH++-K-K++-ATPase inhibitors; -ATPase inhibitors; bismuch(bismuch( 铋剂铋剂 ); sulralfate(); sulralfate( 硫糖铝硫糖铝 ), ), etc.etc. Weaker, combined with Weaker, combined with antimicrobial drugs.antimicrobial drugs.

2. Antimicrobial drugs:2. Antimicrobial drugs: Metronidazole(Metronidazole( 甲硝唑甲硝唑 ); ); Amoxicillin(Amoxicillin( 阿莫西林阿莫西林 ); Tetracycline(); Tetracycline( 四四环素环素 ); Gentamicin (); Gentamicin ( 庆大霉素庆大霉素 ); ); Clarithromycin(Clarithromycin( 克拉霉素克拉霉素 ), ), etc.etc.



misoprostol

The best treatment regimen consists of a 7–14 day regimen of "triple therapy":

1) Bismuth subsalicylate (2 tablets; 262 mg each),2) Tetracycline (500 mg), 3) Metronidazole (250 mg), each taken four times daily for 14 days.

Program 2

Program 1

1) A proton pump inhibitor twice daily, 2) Clarithromycin 500 mg twice daily, 3) Amoxicillin 1 g twice daily. Daily for 7 d.For patients who are allergic to penicillin, metronidazole 500 mg twice daily should be substituted for amoxicillin.


1)A proton pump inhibitor twice daily

2) Bismuth subsalicylate (2 tablets; 262 mg

each),

3) Clarithromycin 500 mg twice daily,

4) Amoxicillin 1 g twice daily

for 14 days.

For patients with resistant infections, "quadruple therapy”


Gastrointestinal drugs

Part2 Part2

Modulators of gastrointestinal functionsModulators of gastrointestinal functions

Abnormalities of gastrointestinal Abnormalities of gastrointestinal functionsfunctions

Nausea and vomiting ConstipationDiarrhea

Modulators of gastrointestinal Modulators of gastrointestinal functionsfunctions

ContentContentss

Antiemetic and prokinetic drugsAntiemetic 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 ))

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 ))

LaxativesLaxatives

1. contact(stimulant) laxatives1. contact(stimulant) laxatives

2. osmotic laxatives2. osmotic laxatives

3. faecal softners(emollients)3. faecal softners(emollients)

延脑的呕吐中枢，可接受来自催吐化学感受区（ CTZ ）、前庭器官、内脏等传入冲动而引发呕吐。已知 CTZ 含有丰富的多巴胺、组胺、胆碱受体，前庭器官有胆碱能、组胺能神经纤维

与呕吐中枢相联。 5- 羟色胺的 5-HT3 亚型受体

通过外周、中枢部位如孤束核也与呕吐有关。

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 受体阻断受体阻断药药 ):):

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 , ,

灭吐灵灭吐灵 ))

DD22 receptor block: antiemetic receptor block: antiemetic

effects(CTZ), and promoting GI motility.effects(CTZ), and promoting GI motility.

Adverse effects: CNS reactions, Adverse effects: CNS reactions,

extrapyra-midal effects, extrapyra-midal effects, etc.etc.

Domperidone(Domperidone( 多潘立酮多潘立酮 , , 吗丁啉吗丁啉 )) DD22 receptor block: promoting GI receptor block: promoting GI

motility.motility.

Adverse effects: headache, prolactinAdverse effects: headache, prolactin

（泌乳素）（泌乳素） , gastric acid , gastric acid


Prokinetic drugsProkinetic drugsMetoclopramide Metoclopramide 甲氧氯普甲氧氯普胺胺Mechanism of action

1) Block D2 receptor, to stimulate 5-HT4 receptors and enhance transmission in cholinergic nerve plexues

2) 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 uses

1) Used for treatment of diabetic gastroparesis

2) Used for the prevention of nausea and vomiting associated with cancer chemotherapy or occurring post-operatively.


Domperidone Domperidone 多潘立多潘立酮酮 Mechanism of action

A peripherial dopamine antagonist

Clinical usesClinical uses 1) Used for treatment of diabetic

gastroparesis 2) Used for the prevention of nausea and

vomiting induced by dyspepsia, chemotherapy, gastroesophageal reflux diseasegastroesophageal reflux disease .

Adverse effectsAdverse effects

Has few side effects because it can not cross the BBBHas few side effects because it can not cross the BBB

锥体外系不良反应少于甲氧氯普胺锥体外系不良反应少于甲氧氯普胺



misoprostol

对非甾体抗炎药引起的消化性溃疡有特效的药物是 ( ) A ． OmeprazoleB ． Magnesium trisilicate（三硅酸镁）C ． MisoprostolD ． Sucralfate（硫糖铝） E ． Domperidone（多潘立酮）

Domperidone（多潘立酮）的止吐作用是通过阻断 ( ) A ． 5-HT3受体B ． M1受体C ． α1受体D．多巴胺受体E ． H2受体

抑酸作用最强的药物是 ( ) A ． Cimetidine（西米替丁）B ． Pirenzepine（哌仑西平）C. OmeprazoleD. Sodium bicarbonate（碳酸氢钠）

Gastrointestinal drugs. Part 1. Drugs used for peptic ulcers Part 2. Modulators of gastroenteric...

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