Drugs Affecting Gastrointestinal Function

OUTLINE

Peptic Ulcer Digestion Vomiting Diarrhea Bile Review-Questions

Ulcer-Background

Epidemiology incidence of a disease: 10%-12%DU > GU (3:1)

EtiologyGeneral consideration: No Acid No UlcerNo Acid No UlcerMain Destroy Factors: HCl, Pepsin, Hp① ② ③Protective Barrier: Mucus-HCO3-

PhysiologyHCl: P-cell, HP-cell, H22, M, M11, G-R, H, G-R, H++-pump-pump

Anti-ulcer Targets

HClMucusHp

Anti-ulcer Classification

I. Antacids--- NeutralizeNeutralize HClII. Gastric Antisecretory Drugs

HCl secretion1. Antagonize Rs. on Parietal CellParietal Cell--- H2,M3,

G2. Inhibitor of HH++-Pump-Pump

III. Protectors of MucosaIV. Agents kill HPHP

Ⅰ. Antacids

Mechanism:Alkalizers——To Neutralize HCl

Agents:Mg(OH)2 Al(OH)3 CaCO3 NaHCO3

Adverse Effect:Systemic alkalosis, Diarrhea , CO2

ConstituentNeutralizing

Capacity

Salt Formed in Stomach

Solubility of Salt

Adverse Effects

NaHCO3 High NaCl HighSystemic alkalosis, fluid retention

CaCO3 Moderate CaCl2 ModerateHypercalcemia, nephrolithiasis, milk-alkali syndrome

Al(OH)3 High AlCl3 LowConstipation, hypophosphatemia; drug adsorption reduces bio-availability

Mg(OH)2 High MgCl2 LowDiarrhea, hypermagnesemia (in patients with renal insufficiency)

Major constituents of antacids

Ⅱ.1. H⑴ 2-R Antagonists

Mechanism: Pharmacologic Effects:

Basal gastric acid nocturnal secretion

Agents:Cimetidine ， Ranitidine ， Famotidine

Adverse Effect:Gynecomastia, prolactin , CYP450 , heada

che

Ⅱ.1. Antimuscarinic Agents⑵ Mechanism:

Blocking M3-R on Parietal Cell, M-R on ECL cell and G cell

Pharmacologic Effects:HCl spasmolysis

Agents:Atropine ， ProbanthinePirenzepine - M1,M2-R selection

Adverse Effect:

Ⅱ.1. Antagonist of G-R⑶

Mechanism:Competing Gastrin-R on Parietal Cell

Pharmacologic Effects:HCl Mucosal

Agents:Proglumide

Adverse Effect:

Ⅱ.2. Proton Pump Inhibitors

Mechanism:H+,K+-ATPase H+ K+

Pharmacologic Effects:HCl & Hp

Agents:Omeprazole （ losec ）LansoprazolePantoprazole ， Rabeprazole

Adverse Effect:

Ⅲ. Mucosal Protective Agents

1. Derivatives of Prostaglandin: Misoprostol (PGE1), Enprostil

Mechanism: HCl ; Pepsin Mucus-HCO3- ; Cytoprotective effect

Pharmacologic Effects: Prevention of ulcers iduced by NSAIDs

Contraindication ： Women with childbearing

2. SucralfateMechanism:

Polymerization & gelatine barrier PGE2

Mucus-HCO3-

Hp

Pharmacologic Effects:Effective in Duodenal Ulcers

Notice:Acid pHEmpty stomach

3. CBS Mechanism:

Pepsin PGE1

Mucus-HCO3-

CoatingHp （ disputed ）

4. Teprenone

5. Marzulene

Ⅳ. Anti-Hp Drugs

90% DU,70% GU --- Helicobacter pylori (G-)

1. Anti-Ulcer Agents:① Bismuth Compounds② Proton Pump Inhibitors③ sucralfate

2. Antibacterial Drugs:① Amoxicillin② Gentamicin③ Metronidazole

Combination Therapy

Therapy of triadOversea

PPI + two Antibacterial Drugs

DomesticCBS + PPI or H2-R Antagonist +

Antibacterial Drug

Digestion Aids

1. Contents of Digestive Juice: Pepsin Pancreatin

2. Helpful Bacterias in Bowel: biofermin

Antiemetic Drugs and Drugs Promoting Gastrointestinal Motility

Nausea and Vomiting mechanism:

Vomiting Center

Chemoreceptor trigger zone

CTZ

Vestibular apparatus

Other areas

Chemical stimuli 5-HT, D2, M1, H1

Stomach and Abdomminal Mus

culatureVomiting

1. Antagonists of Receptors of ①① HH11:: Nucleus of tractus solitarius, vestibulocerebellar p

athway—— Diphenhydramine, Dimenhydrinate

②② M M : : Nucleus of tractus solitarius, CTZ——Scopolamine

③③ DD22 : : CTZ, Nucleus of tractus solitarius, Stomach, Small intestine——Thiethylperazine ， MetoclopramideMetoclopramide

④④ 5-HT5-HT33 : : Stomach, Small intestine, CTZ, Nucleus of tractus solitarius——Ondansetron ， Granisetron

2. Prokinetics ： MetoclopramideMetoclopramide Blocking Gastrointestinal Domperidone D2-R Cisapride ： Ach release↑

Antidiarrheal Drugs and Adsorbents

1. Opium preparation and Derivatives Opiate receptors in Gastrointestinal tract → tone↑motil

ity↓ （ μ ）， secretion↓ （ δ ）， Ach release ↓ Loperamide ： Derivatives of Haloperidol

2. Astringents① Tannalbin② Bismuth subsalicylate, Bismuth subcarbonate

3. Adsorbants① Medicinal Charcoal② Kaolin

Laxatives

1. Contact cathartics Irritant or stimulant → intestinal motility↑ Phenolphthalein, Rhubarb, Senna, Castor oil

2. Osmotic laxatives nonabsorbable → distending → peristalsis MgSO4, Na2SO4, Lactulose, Celluloses

3. Surface-active agents Lubricating, Stool soften Liquid paraffin

Choleretic drug

1. Cholic Acid HMG-CoA reductase (rate limiting enzyme)↓

→ bile salt↑ ， cholesterol ↑ Chenodiol (Chenodeoxycholic acid)

2. MgSO4

cholecystokinin ↑

3. Cinametic acid

4. Anethol trithione

Review-Questions

The classification of drugs used in the treatment of peptic ulceration.

the mechanisms and the agents of each.