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Obat Gastrointestinal

Gastrointestinal DrugsProf. 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 SolvingSeorang 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 ? 5. Apa efek sampingnya ?

Regulation and Function of GI TractGI 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 CellMechanisms regulating secretion of HCl by gastric parietal cells

GI DisordersPeptic ulcer disease (PUD)Gastrointestinal Reflux Disease (GERD)Gastroparesis (Delayed Gastric Emptying)ConstipationDiarrheaIrritable Bowel Syndrome (IBS)Inflammatory Bowel Disease (IBD)

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

H. PyloriHow 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 acidCOX-1COX-2NonselectiveNSAIDCOX-2selectiveInhibitorBody Homeostasis . Gastric integrity. Renal Function . Platelet Function

InflammationPainNeedleman 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; 340:1888-99Drugs used for Peptic Ulcers H2-histamine receptor antagonistsProton pump inhibitors (PPI)SucralfateMisoprostolAntibiotic to eradicate H. pylori

Drugs used for GERDH2-histamine receptor antagonistsProton pump inhibitors (PPI)Promotility agents - Metoclopramide - Cisapride

Mechanisms of action of GI Drugs

Pharmacokinetics of GI drugs

Eradication of H Pylori

Side EffectsH2 Receptor Antagonist - Headache - Diarrhea - Constipation - nauseaProton Pump Inhibitor (PPI), similar to H2 RA - Diarrhea (more frequently)Antacid - constipation (aluminium-containing antacids) - diarrhea (magnesium containing antacids) Mucosal protectant (Sucralfate) - Constipation

Side EffectsMucosal protectant (Sucralfate) - ConstipationProstaglandin (misoprosol) - Diarrhea Promotility agents - Metoclopramide) - parkinsonian side effects, sedation - Cisapride ; torsade de pointes (ventricular arrhythmia)

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