Gastrointestinal Drugs

Prof. DR. dr. Hadyanto Lim, M.Kes, SpFK, FESC,

FIBA
Department of Pharmacology and Molecular Biology
Faculty of Medicine, Methodist University of Indonesia - Medan
Molecular Biology Research, Postgraduate School,
University of Sumatra Utara - Medan

Problem Solving
Seorang wanita berusia 55 tahun datang dengan
keluhan nyeri ulu hati setempat, setelah sarapan pagi.
Nyeri mengisap ini telah berlangsung selama 1 minggu.
Os telah minum obat antasid, namun sering kambuh.
Keluhan ini telah dirasakan selama setengah tahun. Ibu
os juga sering mengeluh nyeri di ulu hati.
Pada pemeriksaan : TD 130/80 mmHg, Temp , 36.5C, RR
20x/menit, HR 70 x/menit. Pertanyaan :
1. Pemeriksaan apa diperlukan untuk menegakkan
diagnosis ?
2. Faktor risiko apa yang menyebabkan penyakit ini ?
3. Bagaimana pengobatan penyakit ini dan komplikasi ?
4. Bagaimana mekanisme kerja (farmakodinamik) dan
farmokinetik
obat H2 histamine receptor antagonist, proton pump
inhibitor ?

Regulation and Function of GI

Tract
GI tracts stores, digests and absorb
nutrients and eliminates wastes.
Regulation of the GI organs is mediated
by intrinsic nerves of the enteric
nervous system, neural activity in the
central nervous system (CNS) and an
array of hormones.

Regulation and Function of GI

Tract

Acid Secretion from the

Parietal Cell

Mechanisms regulating secretion of HCl by gastric parietal

cells

GI Disorders
Peptic ulcer disease (PUD)
Gastrointestinal Reflux Disease
(GERD)
Gastroparesis (Delayed Gastric
Emptying)
Constipation
Diarrhea
Irritable Bowel Syndrome (IBS)
Inflammatory Bowel Disease

Peptic Ulcers
Occur primarily in the stomach and
duodenum at a site where the mucosal
epithelium is exposed to acid and pepsin.
A constant confrontation between acidpepsin and mucosal defense in the
stomach and upper small bowel.
Most patients with DUs have an increase
in acid secretion, patients with GUs often
have normal or low rates of acid secretion.

Peptic Ulcers
astrointestinal Reflux Disease
( GERD )

Esophagitis

Peptic Ulcers
Most peptic ulcers are associated
with either a gram-negative bacillus,
Helicobacter pylori (H pylori), or
chronic use of nonsteroidal
antiiflammatory drugs (NSAIDs).

H. Pylori

How the HP causes Peptic

Ulcers ?
H. pylori is causally associated with PUD.
H pylori infection produces inflammatory
changes in the mucosa, impairs mucosal
defense mechanisms (barrier function)
and increases acid secretion.
Eradication of H pylori cures the disease.
Most patients eliminates the need for
continous antisecretory maintenance
therapy.

The Arachidonic Cascade and COX-1

and COX-2 Inhibition
Arachidonic acid

COX-1

COX-2
Nonselective
NSAID

Body Homeostasis
. Gastric integrity
. Renal Function
. Platelet Function

COX-2
selective
Inhibitor

Inflammation
Pain

Needleman P, et al. J Rheumatol. 1997;24:6-8.

Simon LS, et al. J Clin Rheumatol. 1996;2:135-40

Mechanisms by Which NSAIDs Induce Gastroduodenal Mucosal Injury

Wolfe, MM, et al. N Eng J Med 1999;

340:1888-99

Drugs used for Peptic Ulcers

H2-histamine receptor
antagonists
Proton pump inhibitors (PPI)
Sucralfate
Misoprostol
Antibiotic to eradicate H. pylori

Drugs used for GERD

H2-histamine receptor
antagonists
Proton pump inhibitors (PPI)
Promotility agents
- Metoclopramide
- Cisapride

Mechanisms of action of GI Drugs

Pharmacokinetics of GI drugs

Eradication of H Pylori

Side Effects
H2 Receptor Antagonist
- Headache
- Diarrhea
- Constipation
- nausea
Proton Pump Inhibitor (PPI), similar to H2 RA
- Diarrhea (more frequently)
Antacid
- constipation (aluminium-containing
antacids)
- diarrhea (magnesium containing antacids)

Mucosal protectant (Sucralfate)

- Constipation

Side Effects
Mucosal protectant (Sucralfate)
- Constipation
Prostaglandin (misoprosol)
- Diarrhea
Promotility agents
- Metoclopramide) - parkinsonian side
effects,
sedation
- Cisapride ; torsade de pointes
(ventricular
arrhythmia)

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Drugs to treat Hepatitis