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)  Etiology No Acid No Ulcer General consideration: No Acid No Ulcer Main Destroy Factors: ① HCl, ② Pepsin, ③ Hp Protective Barrier: Mucus-HCO3 -  Physiology P-cell, H 2, M 1, G-R, H + -pump HCl: P-cell, H 2, M 1, G-R, H + -pump

Anti-ulcer Targets  HCl  Mucus  Hp

Anti-ulcer Classification Neutralize I. Antacids--- Neutralize HCl II. Gastric Antisecretory Drugs HCl secretion Parietal Cell 1. Antagonize Rs. on Parietal Cell--- H 2,M 3, G H + -Pump 2. Inhibitor of H + -Pump III. Protectors of Mucosa HP IV. Agents kill HP

Ⅰ. Antacids  Mechanism: Alkalizers——To Neutralize HCl  Agents: Mg(OH) 2 Al(OH) 3 CaCO 3 NaHCO 3  Adverse Effect: Systemic alkalosis, Diarrhea, CO 2

Constituent Neutralizing Capacity Salt Formed in Stomach Solubility of Salt Adverse Effects NaHCO 3 HighNaClHigh Systemic alkalosis, fluid retention CaCO 3 ModerateCaCl 2 Moderate Hypercalcemia, nephrolithiasis, milk-alkali syndrome Al(OH) 3 HighAlCl 3 Low Constipation, hypophosphatemia; drug adsorption reduces bio- availability Mg(OH) 2 HighMgCl 2 Low Diarrhea, hypermagnesemia (in patients with renal insufficiency) Major constituents of antacids

Ⅱ.1. ⑴ H 2 -R Antagonists  Mechanism:  Pharmacologic Effects: Basal gastric acid nocturnal secretion  Agents: Cimetidine ， Ranitidine ， Famotidine  Adverse Effect: Gynecomastia, prolactin, CYP450, headache

Ⅱ.1. ⑵ Antimuscarinic Agents  Mechanism: Blocking M 3 -R on Parietal Cell, M-R on ECL cell and G cell  Pharmacologic Effects: HCl spasmolysis  Agents: Atropine ， Probanthine Pirenzepine - M 1,M 2 -R selection  Adverse Effect:

Ⅱ.1. ⑶ Antagonist of G-R  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 ） Lansoprazole Pantoprazole ， Rabeprazole  Adverse Effect:

Ⅲ. Mucosal Protective Agents 1. Derivatives of Prostaglandin: Misoprostol (PGE 1 ), Enprostil  Mechanism:  HCl ; Pepsin  Mucus-HCO3 - ;  Cytoprotective effect  Pharmacologic Effects:  Prevention of ulcers iduced by NSAIDs  Contraindication ：  Women with childbearing

2. Sucralfate  Mechanism:  Polymerization & gelatine barrier  PGE 2 Mucus-HCO3 -  Hp  Pharmacologic Effects:  Effective in Duodenal Ulcers  Notice:  Acid pH  Empty stomach

3. CBS  Mechanism:  Pepsin  PGE 1 Mucus-HCO3 -  Coating  Hp （ disputed ） 4. Teprenone 5. Marzulene

Ⅳ. Anti-Hp Drugs  90% DU,70% GU --- Helicobacter pylori (G - ) 1. Anti-Ulcer Agents:  Bismuth Compounds  Proton Pump Inhibitors  sucralfate 2. Antibacterial Drugs:  Amoxicillin  Gentamicin  Metronidazole

Combination Therapy  Therapy of triad Oversea  PPI + two Antibacterial Drugs Domestic  CBS + PPI or H 2 -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, D 2, M 1, H 1 Stomach and Abdomminal Musculature Vomiting

1. Antagonists of Receptors of  H 1 :  H 1 : Nucleus of tractus solitarius, vestibulocerebellar pathway——Diphenhydramine, Dimenhydrinate  M :  M : Nucleus of tractus solitarius, CTZ—— Scopolamine  D 2 : Metoclopramide  D 2 : CTZ, Nucleus of tractus solitarius, Stomach, Small intestine——Thiethylperazine ， Metoclopramide  5-HT 3 :  5-HT 3 : Stomach, Small intestine, CTZ, Nucleus of tractus solitarius——Ondansetron ， Granisetron 2. Prokinetics ： Metoclopramide Metoclopramide Blocking Gastrointestinal Domperidone D 2 -R Cisapride ： Ach release ↑

Antidiarrheal Drugs and Adsorbents 1. Opium preparation and Derivatives Opiate receptors in Gastrointestinal tract → tone↑motility↓ （ μ ）， secretion↓ （ δ ）， Ach release ↓ Loperamide ： Derivatives of Haloperidol 2. Astringents  Tannalbin  Bismuth subsalicylate, Bismuth subcarbonate 3. Adsorbants  Medicinal Charcoal  Kaolin

Laxatives 1. Contact cathartics  Irritant or stimulant → intestinal motility↑  Phenolphthalein, Rhubarb, Senna, Castor oil 2. Osmotic laxatives  nonabsorbable → distending → peristalsis  MgSO 4, Na 2 SO 4, 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. MgSO 4 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.