gastrointestinal drugs weiwei hu e-mail:huww@zju.edu.cn phone: 0571-88208226

Gastrointestinal drugsGastrointestinal drugs

Weiwei HU

E-mail:huww@zju.edu.cn

Phone: 0571-88208226

1.Hepatic, pancreatic and 1.Hepatic, pancreatic and biliary disordersbiliary disorders

2. Acid-peptic disorders

3.Gastrointesinal motilitydisorders

4. Inflammatory bowel diseases

Gastrointestinal drugs

1. Drugs used for 1. Drugs used for acid-peptic

disorders

2. Modulators of gastrointestinal 2. Modulators of gastrointestinal

functionsfunctions

1. Acid-peptic disorders

1) Peptic ulcer disease (PUD, 消化性溃疡 )

2) Gastroesophageal reflux disease (GERD)

3) Drug-induced mucosal injury, especially by non-steroidal anti-inflammatory drugs (NSAIDs)

4) Pathologic acid-hypersecretory conditions (e.g. Zollinger-Ellison syndrome)

5) Acute stress ulcers

1)

The feature of peptic ulcer disease: High incidence, Recurrence frequently, Drug treatment is the main way

Symptoms:

Upper abdominal burning or hunger painEmesia ( 呕吐 ), belching ( 嗳气 )

Ulcer complicationUlcer bleeding ( 出血 )

Ulcer perforation ( 穿孔 )

Pyloristenosis ( 幽门狭窄 )

Canceration ( 癌变 )

2) Gastroesophageal reflux disease (GERD)

Abnormal reflux in the esophagus

3) Drug-induced mucosal injury, especially by non-steroidal anti-inflammatory drugs (NSAIDs)

4) Pathologic acid-hypersecretory conditions (e.g.Zollinger-Ellison syndrome)

Tumor

Gastrin

Gastic acid

Peptic ulcer

5) Acute stress ulcers

2. Gastric acid secretion and regulation2. Gastric acid secretion and regulation

Gastric cells of mucosa

(1)Surface epithelial cells (secrete mucus)

(2)Mucus neck cells (secret mucus and are the

source of proliferating cells);

(3)Chief cells (secret pepsinogens)

(4)G cells (release gastrin in the antrum);

(5)Parietal cells in the gastric fundus ( secrete

HCI and intrinsic factor)

2. Gastric acid secretion and regulation2. Gastric acid secretion and regulation

Basolateral membane

(the proton pump)

Mucus-bicarbonate barrier

Helicobacter pylori infection

Gastric acidGastric acid

PepsinPepsin

Helicobacter pyloriHelicobacter pylori

Mucus

bicarbonate

Mucosa

2.Pathogenesis of peptic ulcers

Aggressive factors Defensive factors

Pathogenesis of peptic ulcers

Treatment approaches

(1)Increased gastric Increased gastric acid secretionacid secretion

(3)Inadequate mucosal (3)Inadequate mucosal defense against gastric defense against gastric acidacid

(2)Infection with gram-(2)Infection with gram-negative negative Helicobacter Helicobacter pyloripylori

(1)Reducing secretion of (1)Reducing secretion of gastric acid or neutralizing gastric acid or neutralizing the acidthe acid

(3)Protecting the gastric (3)Protecting the gastric mucosa from damagemucosa from damage

(2)Eradicating (2)Eradicating H. H. pyloripylori infection infection

(1) Antacids: (1) Antacids: neutralizing the acidneutralizing the acid

(2) Drugs suppressing gastric acid secretion(2) Drugs suppressing gastric acid secretion

①①Muscarinic receptor antagonistsMuscarinic receptor antagonists

②②HH22 receptor antagonists receptor antagonists

③③Gastrin receptor antagonistsGastrin receptor antagonists

④ ④ HH++-K-K++-ATPase inhibitors (proton pump -ATPase inhibitors (proton pump

inhibitors)inhibitors)

(3)Antimicrobial drugs ((3)Antimicrobial drugs (Helicobacter pyloriHelicobacter pylori))

(4)Mucosal protective drugs(4)Mucosal protective drugs

3.Drugs used for peptic ulcers

(1) (1) Antacids Antacids (Weak bases)

Chemistry of antacids:

Salts of aluminum (aluminum hydroxide) ,

Salts of magnesium (carbonate, hydroxide,

trisilicate) , aluminum magnesium carbonate

(Al2Mg6(OH)16CO3·4H2O)

calcium(carbonate)

sodium (bicarbonate)

(1) (1) Antacids Antacids

× Antacids

Mechamism of action

(the proton pump)

(1) Antacids(1) Antacids

1. 1. Pharmacological effectPharmacological effect

Neutralizing gastric acid, diminish gastric acidity and Neutralizing gastric acid, diminish gastric acidity and

inactivate pepsininactivate pepsin （胃蛋白酶）（胃蛋白酶） activityactivity

The effect depends on the dose and dosing frequency.The effect depends on the dose and dosing frequency.

Starting effect within 5-15 min after taking the drugs.Starting effect within 5-15 min after taking the drugs.

2. 2. Clinical usesClinical uses

Commonly used for dyspepsia symptom and Commonly used for dyspepsia symptom and

minor episodes of heartburn.minor episodes of heartburn.

3. 3. Adverse effectsAdverse effects

(1) Constipation and stomach cramp (salt of aluminum)

(2) Diarrhea (salt of magnesium )

Combination products such as maalox

(3) Hypercalcium which can cause renal failure (Calcium)

(4) Hypernatremia (sodium-containing antacids)

All antacids are generally regarded as safe in pregnancy.

4.4. Drug interactions Drug interactions

Avoid concurrent administration of antacids and a variety of Avoid concurrent administration of antacids and a variety of

drugs .drugs .

(1) Affect rates of dissolution and absorption, bioavailbility, (1) Affect rates of dissolution and absorption, bioavailbility,

and renal elimination of many drugsand renal elimination of many drugs

(2) By binding to drugs (for example, tetracycline(2) By binding to drugs (for example, tetracycline 四环素四环素 ), ),

form insoluble complexes that are not absorbedform insoluble complexes that are not absorbed

Adminstration and dosage

(1) Take antacids after meals and at bedtime

(2) Should taken continuously for a long time

(3) To help avoid or reduce drug interaction, other

medication should not be taken within 1-2 hours

of taking an antacids

CimetidineCimetidine

NNN

CH2SCH2CH2NHCNHCH3

H

H3C

CN

(2) Drugs affecting gastric acid secretion(2) Drugs affecting gastric acid secretion

②② HH22 receptor antagonists receptor antagonists

(Proton pump)×

cimetidinecimetidine

Mechamism of action

1. 1. Pharmacological effectPharmacological effect

Blocking HBlocking H2 2 receptors, decreasing Hreceptors, decreasing H++ secretion secretion

2. 2. Clinical usesClinical uses

1) Duodenal and gastric ulcer1) Duodenal and gastric ulcer

2) Zollinger-Ellison syndrome,2) Zollinger-Ellison syndrome,

3) Acute stress ulcers3) Acute stress ulcers

4) Gastroesophageal reflux disease (heartburn)4) Gastroesophageal reflux disease (heartburn)

CimetidineCimetidine

3. 3. Adverse effectsAdverse effects (1) common side effects: (1) common side effects: constipation, diarrhea, constipation, diarrhea,

tiredness, muscular pain, tiredness, muscular pain, etc.etc.

(2) CNS effects: (2) CNS effects: headache, dizziness, confusion, headache, dizziness, confusion, hallucination, hallucination, etc.etc. (elderly, long-term uses) (elderly, long-term uses)

(3)Endocretion effects: (3)Endocretion effects: antiandrogenantiandrogen （ 抗 雄 激 素 ）（ 抗 雄 激 素 ） , , gynecomastia, galactorrheagynecomastia, galactorrhea,,reduced sperm count, and reduced sperm count, and male sexual dysfunctionmale sexual dysfunction

4.4. Drug interactions Drug interactions Inhibiting hepatic PInhibiting hepatic P450450, , raising plasma concentrations of raising plasma concentrations of

warfarin, phenytoin, diazepam, propranolol, quinidine warfarin, phenytoin, diazepam, propranolol, quinidine and theophyllineand theophylline

CimetidineCimetidine

5. Elimination

Urinary excretion is the principal route of

elimination of cimetidine, the dose should be

modified in patients with renal impairment.

Other HOther H22 receptor antagonists receptor antagonists

Ranitidine Ranitidine

4-10 times more potent than cimetidine4-10 times more potent than cimetidine

Minimal side effects, weakly inhibiting CYPMinimal side effects, weakly inhibiting CYP

Famotidine Famotidine

7-10 times more potent than ranitidine, but no 7-10 times more potent than ranitidine, but no inhibiting CYPinhibiting CYP

NizatidineNizatidine

Bioavailability is near 100%, principally eliminated Bioavailability is near 100%, principally eliminated by kidneyby kidney

Omeprazole Omeprazole 奥美拉唑奥美拉唑

N

OCH3H3C CH3

CH2

OCH3

S

O

H

N

N

(2) Drugs affecting gastric acid secretion(2) Drugs affecting gastric acid secretion

③③HH++-K-K++-ATPase inhibitors -ATPase inhibitors

(proton pump inhibitors)(proton pump inhibitors)

Omepranzole

×

(the proton pump)

1. 1. Pharmacological effectsPharmacological effects (1) Inhibiting gastric acid secretion by various stimuli (1) Inhibiting gastric acid secretion by various stimuli

(histamine, gastrin, aspirin, ethanol, stress)(histamine, gastrin, aspirin, ethanol, stress) (2) Inhibiting (2) Inhibiting H. pyloriH. pylori ((3) protection for gastric mucosa3) protection for gastric mucosa

2. 2. Clinical usesClinical uses (1) Highly effective for duodenal and gastric ulcer: (1) Highly effective for duodenal and gastric ulcer:

relieving symptoms,relieving symptoms, promoting healing of ulcers, with promoting healing of ulcers, with antimicrobial regimens to eradicate antimicrobial regimens to eradicate H. pylori H. pylori

(2) Gastro-esophageal reflux disease(2) Gastro-esophageal reflux disease (3) Zollinger-ellison syndromeUsed(3) Zollinger-ellison syndromeUsed

OmeprazoleOmeprazole

3. 3. Adverse effectsAdverse effects

(1) Side effects: (1) Side effects: nausea, headache, diarrhea, constipation and nausea, headache, diarrhea, constipation and

rash occur but are uncommonrash occur but are uncommon

(2) Increase of gastric carcinoid tumor: (2) Increase of gastric carcinoid tumor: prolongated prolongated

hypochlorhydria and secondary hypergastrinemia hypochlorhydria and secondary hypergastrinemia (only (only

found by animal experiments)found by animal experiments)

(3) Others: (3) Others: gynecomastia gynecomastia (( 男性乳房发育男性乳房发育 )),,

hypersensitivityhypersensitivity

4.4. Drug interactions Drug interactions

It is metabolized by hepatic P450; It is metabolized by hepatic P450;

Inhibiting hepatic P450, Inhibiting hepatic P450, raising plasma concentrations of raising plasma concentrations of

warfarin, phenytoin, diazepam, warfarin, phenytoin, diazepam, etc.etc.

OmeprazoleOmeprazole

Others proton pump inhibitorsOthers proton pump inhibitors

Non-selective: atropine (block M3 receptor in Parietal cells, block M1 receptor in ganglion, block M receptors in ECL and G cells), seldom use now.

Selective: pirenzepine (block M1 receptor)

M receptor antagonistsM receptor antagonists

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

Effects:Effects: Protecting the gastric and duodenal Protecting the gastric and duodenal mucosa from damage by acid and pepsin mucosa from damage by acid and pepsin

Misoprostol Misoprostol 米索前列醇米索前列醇Sucralfate Sucralfate 硫糖铝硫糖铝Colloidal bismuth subcitrateColloidal bismuth subcitrate 胶体次枸橼胶体次枸橼酸铋酸铋

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 E1 analogues

MisoprostolMisoprostol 米索前列醇米索前列醇

1. 1. Pharmacological effectsPharmacological effectsInhibiting gastric acid secretionInhibiting gastric acid secretion

Promoting mucus and HCOPromoting mucus and HCO33-- secretion, and mucosal repair secretion, and mucosal repair

2. 2. Clinical usesClinical usesOnly approved for the prevention of NSAIDs-induced gastricOnly approved for the prevention of NSAIDs-induced gastricUlcer.Ulcer.

3. 3. Adverse effectsAdverse effectsSide effects (13%): abdominal pain, diarrhea, headache, nauseaSide effects (13%): abdominal pain, diarrhea, headache, nausea

etc.etc.

Contraindicated in pregnancy womenContraindicated in pregnancy women (Abortifacient (Abortifacient 堕胎 堕胎 property)property)

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

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

Sucralfate

A sulfated disaccharide （二糖） complex of aluminum hydroxide

1. 1. Pharmacological effectsPharmacological effects1) Binding to tissue 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 more effective agents (proton pump inhibitors. Gastro-esophageal reflux disease. H pylori infection. Take sucralfate 1 hour before meals Four times a day before meals and at bedtime

3. 3. Adverse effectsAdverse effectsConstipation occurs in 2% due to the aluminum salt, not together with alkaline agents

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

Sucralfate

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

Bismuth Compounds

Colloidal bismuth subcitrate (CBS)

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 uses

1) Peptic ulcers, chronic gastritis, duodenitis,

functional dyspepsia

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 Compounds

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

Smectite

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.

(4) Antimicrobial drugs (4) Antimicrobial drugs (for (for Helicobacter pyloriHelicobacter pylori))

1. 1. Anti-ulcer drugsAnti-ulcer drugs HH++-K-K++-ATPase inhibitors; bismuch ; sulralfate-ATPase inhibitors; bismuch ; sulralfate

Weaker, combined with antimicrobial drugsWeaker, combined with antimicrobial drugs

2. 2. AntibioticsAntibiotics metronidazole metronidazole (( 甲硝唑甲硝唑 )); ; amoxicillinamoxicillin (( 阿莫西林阿莫西林 ));;

tetracyclinetetracycline (( 四环素四环素 )); ; gentamicingentamicin (( 庆大霉素庆大霉素 )); ;

clarithromycin clarithromycin (( 克拉霉素克拉霉素 ))

The best treatment regimen consists of a 10–14 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. 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) Tetracycline (500 mg),

4) Metronidazole (250 mg), each taken four times daily

for 14 days.

For patients with resistant infections, "quadruple therapy”

Gastrointestinal drugs

1. Drugs used for 1. Drugs used for acid-peptic

disorders

2. Modulators of gastrointestinal 2. Modulators of gastrointestinal

functionsfunctions

Abnormalities ofAbnormalities of gastrointestinal functionsgastrointestinal functions

Nausea and vomiting ConstipationDiarrhea

Modulators ofModulators of gastrointestinal functionsgastrointestinal functions

1. Antiemetic drugs1. Antiemetic drugs

2. Prokinetic drugs 2. Prokinetic drugs

3. Anti-diarrheals3. Anti-diarrheals

4. Laxatives4. Laxatives

Antiemetic drugsAntiemetic drugs

There are various sources of input to the vomiting center:1. The chemoreceptor trigger zone at the base of the fourth ventricle has numerous

dopamine D2 receptors, serotonin 5-HT3 receptors, opioid receptors, acetylcholine receptors, and receptors for substance P. Stimulation of different receptors are involved in different pathways leading to emesis, in the final common pathway substance P appears involved.

2. The vestibular system, which sends information to the brain via cranial nerve VIII (vestibulocochlear nerve), plays a major role in motion sickness, and is rich in muscarinic receptors and histamine H1 receptors.

3. The Cranial nerve X (vagus nerve) is activated when the pharynx is irritated, leading to a gag reflex.

4. The Vagal and enteric nervous system inputs transmit information regarding the state of the gastrointestinal system. Irritation of the GI mucosa by chemotherapy, radiation, distention, or acute infectious gastroenteritis activates the 5-HT3 receptors of these inputs.

5. The CNS mediates vomiting that arises from psychiatric disorders and stress from higher brain centers.

Antiemetic drugsAntiemetic drugs

1. H1 antagonists: sedative effect, antiemetic effect, use for motion sickness and Meniere disease.

2. M receptor antagonists: scopolamine, use for motion sickness.

3. D receptor antagonists: chloropromazine, thiethylperazine ( 硫乙拉嗪 ).

4. 5-HT3 receptor antagonists: ondansetron, granisetron, tropisetron, et al. Use for vomiting induced by chemotherapy for cancer, but not for motion sickness.

GI tract smooth muscle cellsGI tract smooth muscle cells

NANCneuron

Cholinergic neuron

Post-ganglionic primary motor neuron

Prokinetic drugsProkinetic drugs

prokinetic drugsprokinetic drugs

Metoclopramide 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 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.

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)

MetoclopramideMetoclopramide

Domperidone Domperidone 多潘立酮多潘立酮

prokinetic drugsprokinetic drugs

Mechanism of action

A peripherial dopamine antagonist, has no procholinergic

effects

Adverse effectsAdverse effects

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

Increased serum prolactin levels ( 6% of patients)

Rare cases of prolongation of QT interval.

Anti-diarrhealsAnti-diarrheals

Modulators ofModulators of gastrointestinal functionsgastrointestinal functions

Diarrhea

1) An increase in the active secretion, or an inhibition of absorption

2) Abnormally high motility

Modulators ofModulators of gastrointestinal functionsgastrointestinal functions

1. Antimotility drugsAntimotility drugs

2. AstringentsAstringents

3. AbsorbantsAbsorbants

Anti-diarrhealsAnti-diarrheals

Antimotility drugs: Antimotility drugs:

Mechanisms: Mechanisms: Agonists for Agonists for receptors in GI receptors in GI

tracttract

(1) Opium preparation(1) Opium preparation

(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 easly as as easly as

most opioids do and is relatively selective for peripheral opioid most opioids do and is relatively selective for peripheral opioid

receptors. Hasreceptors. Has CNS effects at larger doses) CNS effects at larger doses)

Anti-diarrhealsAnti-diarrheals

(3) Loperamide (3) Loperamide 洛哌丁胺洛哌丁胺

Anti-diarrhealsAnti-diarrheals

Antimotility drugs:Antimotility drugs:

It is two to three times potent than It is two to three times potent than

diphenoxylate, and its action is more rapid diphenoxylate, and its action is more rapid

in onset and more prolonged. in onset and more prolonged.

Use for acute or chronic diarrhea but not Use for acute or chronic diarrhea but not

induced by infection.induced by infection.

It has less CNS or cardiovascular effectsIt has less CNS or cardiovascular effects .

Astringents:Astringents:

Mechanism:Mechanism: astrictionastriction

(1)(1) Tannalbin Tannalbin 鞣酸蛋白鞣酸蛋白

(2) Bismuch subsalicylate; bismuch(2) Bismuch subsalicylate; bismuch

subcarbonate (subcarbonate ( 铋制剂铋制剂 ))

AbsorbantsAbsorbants ：： (1) Medical charchol (1) Medical charchol 药用炭（活性炭）药用炭（活性炭） (2) Agysical (2) Agysical 矽炭银矽炭银

Anti-diarrhealsAnti-diarrheals

Modulators ofModulators of gastrointestinal functionsgastrointestinal functions

Constipation

LaxativesLaxatives

Treatment

1) Increase the intake of fluids and dietary fiber Regular exercise

2) Laxatives

3) Physical intervene

An decrease in the active secretion, or an enhancement of absorption

Modulators ofModulators of gastrointestinal functionsgastrointestinal functions

2. Osmotic laxatives 2. Osmotic laxatives （渗透性泻药）（渗透性泻药）

3. Emollient3. Emollient Laxatives Laxatives （润滑性泻药）（润滑性泻药）

LaxativesLaxatives

1. Contact laxatives 1. Contact laxatives （接触性、刺激性泻药）（接触性、刺激性泻药）

4. Bulk-forming Laxatives 4. Bulk-forming Laxatives （膨胀性、容积性泻药）（膨胀性、容积性泻药）

LaxativesLaxatives

Phenolphthalein Phenolphthalein 酚酞酚酞 ( No longer used because of concerns about carcigenicity)( No longer used because of concerns about carcigenicity)

Bisacodyl Bisacodyl 必沙可啶必沙可啶 (It is active after deacetylation, stimulating enteric nerves to cause (It is active after deacetylation, stimulating enteric nerves to cause

colonic mass movements; increases fluid and NaCl secretion. )colonic mass movements; increases fluid and NaCl secretion. )

1. 1. Contact laxatives Contact laxatives （接触性泻药）（接触性泻药）

LaxativesLaxatives

Anthraquinones 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）

1. 1. Contact laxatives Contact laxatives （接触性泻药）（接触性泻药）

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 硫酸硫酸镁镁 ;;

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. Osmotic laxatives 2. Osmotic laxatives （渗透性泻药）（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. Emollient3. Emollient Laxatives Laxatives （润滑性泻药）（润滑性泻药）

Liquid petrolatum

( Lubricate the fecal mass, prevent excessive dehydration of the material , and may inhibit water reabsorption by coating the gut wall)

Celluloses: used for functional constipation

4. Bulk-forming Laxatives 4. Bulk-forming Laxatives （膨胀性、容积性泻药）（膨胀性、容积性泻药）