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
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Gastrointestinal Drugs
Prof. DR. dr. Hadyanto Lim, M.Kes, SpFK, FESC, FIBADepartment 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.
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 ? 5. Apa efek sampingnya ?
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
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 acid-pepsin 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 Gastrointestinal Reflux Disease
Esophagitis
( GERD )
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
NonselectiveNSAID
COX-2selectiveInhibitor
Body Homeostasis . Gastric integrity. Renal Function
. Platelet Function
InflammationPain
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