The ROLE OF PPI IN THE

MANAGEMENT of

GERD
Wizhar Syamsuri

Division of Internal Medicine
Putra Bahagia Hospital

Apa yang dimaksud
GastroEsophageal Reflux Disease ?
GERD adalah suatu
keadaan dimana isi
lambung /duodenum
bergerak berbalik arah
masuk ke esophagus
(reflux) dan
menimbulkan keluhan.

Physiologic vs Pathologic
Physiologic GERD



Postprandial
Short lived
Asymptomatic
No nocturnal sx

Pathologic GERD


Symptoms
Mucosal injury
Nocturnal sx

The overall definition of GERD and
its constituent syndromes (Figure 2)

Vakil N et al. Am J Gastroenterol 2006; 101: 1900 - 1920

Incidence
It is one of the most common conditions
affecting the gastrointestinal system.
– Anywhere from 36-77% of people have symptoms of
GERD (heartburn, regurgitation of acid etc.) spread
equally between men and women.

7% have daily heartburn
14-20% have weekly heartburn
15-50% have monthly heartburn

a systematic review Epidemiology of gastro-oesophageal reflux disease . H B El-Serag. M-A Wallander and S Johansson 2005.Epidemiology GERD J Dent.54.710-717 Gut .

.

Mechanisms of GERD (3) Intrinsic Mucosal Abnormalities Abnormal esophageal gland secretion Impaired mucosal resistance Defective Antireflux Barrier LES Hypotension/incompetence Increased Transient Relaxation Hiatal Hernia Ineffective Esophageal Clearance Defective motility Defects in saliva Recumbency Delayed Gastric Emptying .

tight sensation felt beneath the lower sub sternum and spreads upward to throat or jaw Felt intermittently Aggravated by change in position Promt relief by antacids Relieved by milk. or water .Symptoms of Classic GERD Heartburn (pyrosis) Most common clinical manifestation Burning. alkaline substances.

Regurgitation – Effortless return of food or gastric contents from stomach into esophagus or mouth – Described as hot. or sour liquid coming into the mouth or throat Gastric symptoms such as – Early satiety. postmeal bloating. nausea. and vomiting – Related to delayed gastric emptying . bitter.

Albuterol. peppermint as well as alcohol and use of tobacco products can cause or worsen symptoms.Symptoms typically occur after eating a meal and… – can be especially noticeable with a large meal or spicy foods. – Symptoms made worse… Fatty foods. Theophylline. straining or sleeping. . and Calcium channel blockers can also cause symptoms of GERD. coffee. Symptoms may be relieved by antacids. chocolate. Symptoms often are worse – when lying flat.

The GERD symptom pattern is similar in patients with and without esophagitis Heartburn (100%) Epigastric pain Regurgitation Nausea Belching Bloating Scale=% of patients with symptom without esophagitis with esophagitis Abdominal pain Carlsson et al 1998b .

Complications of GERD Erosive/ulcerative esophagitis Esophageal (peptic) stricture Barrett’s esophagus Adenocarcinoma .

20% Barrett’s Esophagus 10 .Endoscopic Spectrum of GERD Normal 40-50% Esophagitis 30-50% Stricture 10 .20% .

Peptic Stricture Barium Swallow Endoscopy .

scarring. strictures Biopsy and cytologic specimens Differentiate carcinoma from Barrett’s esophagus Esophageal manometric (motility) studies – Measure pressure in esophagus and LES .Diagnostic Studies History and PE Barium swallow – Can detect protrusion of gastric fundus Upper GI endoscopy – – – Useful in assessing LES competence Degree of inflammation.

Monitoring pH – Laboratory or 24-hour ambulatory – Determine esophageal pH using specially designed probes High-dose proton pump inhibitor treatment for 2 weeks can be used as a first step in diagnosis of GERD ( EMPIRIC THERAPY ) Radionuclide tests – Detect reflux of gastric contents – Rate of esophageal clearance .

Endoscopy Indications for endoscopy – Alarm symptoms Dysphagia Early satiety GI bleeding Odynophagia Vomiting Weight loss Iron deficiency anemia – – – Empiric therapy failure Preoperative evaluation Detection of Barrett’s esophagus .

.Upper endoscopy – Most commonly used test to evaluate the esophagus and stomach. – Requires mild sedation – Requires technical skill and experience – Most accurate way to evaluate damage to or inflammation of the upper gastrointestinal tract.

Tipe GERD Patients with GERD 100% Patients with NERD 60% Patients with esophagitis 40% Patients without complications 35% Patients with complications 5% Adapted from Quigley 2001 .

serak. batuk. nyeri dada dan gejala extra-esophageal seperti . .yang disebabkan reflux dari lambung/usus dan tidak ada kerusakan jaringan pada pemeriksaan upper endoscopy.asthma. termasuk didalamnya heartburn .regurgitasi .NERD Didefinisikan dengan adanya gejalagejala umum.

Klasifikasi Los Angles Derajat kerusakan Gambaran Endoskopi A Erosi kecil-kecil pada mukosa esofagus dengan diameter < 5 mm B Erosi pada mukosa/lipatan mukosa dengan diameter > 5mm tanpa saling berhubungan C Lesi yang konfluen tetapi mengenai/ mengelilingi seluruh lumen D Lesi mukosa esofagus yang bersifat sirkumferensial (mengelilingi seluruh lumen esofagus) .Tabel 1.

that does not extend between the tops of two mucosal folds Grade D One (or more) mucosal break that is continuous between the tops of two or more mucosal folds. no longer than 5 mm.The LA Classification system for the endoscopic assessment of reflux esophagitis Grade A Grade B One (or more) mucosal break. that does not extend between the tops of two mucosal folds Grade C One (or more) mucosal break. more than 5 mm long. but which involves less than 75% of the circumference One (or more) mucosal break that involves at least 75% of the esophageal circumference Lundell et al 1999 .

D E Esofagus normal Esofagitis ringan Esofagitis sedang Esofagitis berat Esofagus Barret . B. D.A B C A. E. C.

.

Treatment of GERD (Collaborate Cares) Goal of Treatment Eliminate symptoms Heal esophagitis Manage or prevent complications Maintain remission .

alcohol. if appropriate Small frequent meals Elevate HoB 30o (4-6 inches) Do not lie down for 2 to 3 hours after eating Avoid late-night eating (2-3 hs of bedtime) Evaluate effectiveness of medications Observe for side effects of medications . carbonated beverages. coffee and tea Stress reduction techniques Weight reduction. peppermint.Lifestyle modifications (1) Corner stone of GERD therapy Avoid factors that cause reflux – – – Stop smoking Avoid alcohol and caffeine Avoid acidic foods Modify diet – Eat more frequent but smaller meals – Avoid fatty/fried food. chocolate.

Start with antacids and OTC H2R blockers and progress to prescription H2R blockers and finally PPIs Step down – Start with PPI and titrate down to prescription H2R blockers and finally OTC H2R blockers and antacids Step-up Approaches Step-down Approaches PPI ( standard dose ) H2RA ( standar dose ) H2RA ( anti-reflux dose ) .Drug Therapy (2) Two approaches 1. Step up – 2.

Proton pump inhibitors (PPI) Decrease gastric HCl acid secretion Promote esophageal healing in 80% to 90% of patients May be beneficial in ↓ esophageal strictures Headache: Most common side effect .

Treatment H2RAs vs PPIs – 12 week freedom from symptoms 48% vs 77% – 12 week healing rate 52% vs 84% – Speed of healing 6%/wk vs 12%/wk .

esomeprazole (Nexium). lansoprazole. – Symptom relief in 90% – Healing 80-90% – Maintenance of remission 70-95% Equally effective in >90% of individuals Long term safety issues resolved More cost effective than H2RAs in complicated or moderate to severe disease .Proton Pump Inhibitors omeprazole. pantoprazole. rabeprazole (Pariet).

80-90% with PPI’s 40-50% of patients require PPI’s for maintenance of remission The lowest effective dose is therapeutic goal Cost effectiveness is determined by efficacy not price of drug .Maintenance Therapy for GERD For patients with complicated disease 25-40% maintained in remission with H2RAs vs.

Effectiveness of Medical Therapies for GERD Treatment Response Lifestyle modifications/antacids 20 % H2-receptor antagonists 50 % Single-dose PPI 80 % Increased-dose PPI up to 100 % .

0005 .% esophagitis cases healed PPIs are the most effective drugs for the initial treatment of GERD 100 PPIs 80 60 H2RAs 40 Placebo 20 0 2 4 6 8 Weeks of treatment 10 12 Chiba et al. Gastroenterology 1997 p < 0.

Surgical Therapy Surgical therapy – Reduce reflux of gastric contents by enhancing integrity of LES – Most performed laparoscopically Surgical therapy – Necessary if Conservative therapy fails Hiatal hernia present Esophageal stricture and stenosis Chronic esophagitis Bleeding Surgical therapy – Fundus of stomach is wrapped around lower portion of esophagus Reinforce and repair defective barrier – Example: Nissen fundoplication .

Efektivitas Terapi Obat-obatan Golongan Obat Mengurangi Gejala Penyembuhan Lesi Esofagitis Mencegah Komplikasi Mencegah Kekambuhan Antasid +1 0 0 0 Prokinetik +2 +1 0 +1 Antagonis reseptor H2 +2 +2 +1 +1 Antagonis reseptor H2+ prokinetik +3 +3 +1 +1 Antagonis reseptor H2 dosis tinggi +3 +3 +2 +2 Penghambat pompa proton +4 +4 +3 +4 Pembedahan +4 +4 +3 +4 .Tabel 2.

Treatment Modifications for Persistent Symptoms Improve compliance Optimize pharmacokinetics – Adjust timing of medication to 15 – 30 minutes before meals (as opposed to bedtime) – Allows for high blood level to interact with parietal cell proton pump activated by the meal Consider switching to a different PPI .

3. TR Technical Review. antireflux surgery should be recommended as an alternative Twice-daily PPI therapy as an empirical trial for patients with suspected reflux chest pain syndrome after a cardiac etiology has been carefully considered * U. 2. but intolerant of. which are more effective than placebo Long-term use of PPIs for the treatment of patients with esophagitis once they have proven clinically effective.1391 . Preventive Services Task Force Grades . 135: 1383 . symptomatic relief & maintaining healing of esophagitis).S. H2RAs Histamine Receptor Antagonists Kahrilas PJ et al.AGA TR & MPS on Management of GERD* 1.Grade A recommendations (strongly recommended based on good evidence that it improves important health outcomes) AGA American Gastroenterological Association. 5. Antisecretory drugs for the treatment of patients with esophageal GERD syndromes (healing esophagitis. Long-term therapy should be titrated down to the lowest effective dose based on symptom control When antireflux surgery & PPI therapy are judged to offer similar effectiveness in a patient with an esophageal GERD syndrome. Gastroenterology 2008. MPS Medical Position Statement. PPI therapy should be recommended as initial therapy because of superior safety When a patient with an esophageal GERD syndrome is responsive to. 4. PPIs are more effective than H2RAs. In these uses. PPIs Proton Pump Inhibitors. acid suppressive therapy.

2004 .Terapi Empiris Dinamakan juga PPI test Dosis ganda PPI 1-2 minggu Positif. bila keluhan hilang 75% dalam 1 minggu Konsensus GERD PGI.

Bytzer* & A. L.August 2004 S S : symptom recurrence .Treatment option in GERD Continuous Maintenance (month.year) Intermittent Courses S (weeks) S On-demand (days) S S S S P. Blum† . Volume 20 Page 389 . Rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease Alimentary Pharmacology & Therapeutics.

Blum† . Bytzer* & A.An Algorithm Approach On-Demand strategy not appropriate for all GERD patients. Rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease Alimentary Pharmacology & Therapeutics.August 2004 . Algorithm needed to specify: * Initial evaluation * Treatment protocols * Follow-up protocols P. Volume 20 Page 389 . L.

Bytzer* & A. Blum† .Endoscopy not required PPI standard dose 2 – 4 weeks Failure Endoscopy P.August 2004 Success PPI on demand . Rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease Alimentary Pharmacology & Therapeutics. L. Volume 20 Page 389 .

Volume 20 Page 389 . Blum† . Rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease Alimentary Pharmacology & Therapeutics.August 2004 . L. Bytzer* & A.Endoscopy NERD Mild erosive esofagitis Severe erosive esofagitis PPI 4 – 8 weeks Success: Continuous PPI P.

Bytzer* & A. Volume 20 Page 389 .Endoscopy NERD Mild erosive esofagitis PPI 4 – 8 weeks Success: On – Demand PPI P. Rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease Alimentary Pharmacology & Therapeutics. Blum† . L.August 2004 Severe erosive esofagitis .

L. Rationale and proposed algorithms for symptom-based proton pump inhibitor therapy for gastro-oesophageal reflux disease Alimentary Pharmacology & Therapeutics. Blum† .August 2004 Failure: Prolonged therapy . Volume 20 Page 389 .Endoscopy NERD Mild erosive esofagitis Severe erosive esofagitis PPI 4 – 8 weeks Success: On – Demand PPI P. Bytzer* & A.

Pantoflickova D. 56: 57-70 . Differences in pH-Dependent Activation Rates of Substituted Benzimidazoles and Biological in vitro Correlates. 17: 1507-1514 2. et al. Pharmacology 1998.Kromer W et al. Aliment Pharmacol Ther 2003. Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors.HARI 1 – AKTIFASI PPI 3 6 1.

03) Hal ini dibuktikan dengan nilai tengah pH 24 jam pertama sebesar 3.4 pada kelompok yang mendapatkan pengobatan dengan Pariet 20mg dan secara nyata lebih tinggi dibanding PPI lainnya (p≤0. et al. Aliment Pharmacol Ther 2003. 17: 1507-1514 .03) 3 Pantoflickova D.HARI 1 – CEPAT MENGENDALIKAN ASAM Pada HARI 1 Secara nyata. Pariet 20mg lebih kuat dalam menghambat sekresi asam dibanding PPI lainnya (p≤0. Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors.

baik keluhan SIANG atau MALAM hari. 16: 479-485 . A randomized. et al. comparative study of standard-dose rabeprazole and highdose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002. double-blind. A randomized.. double blind & comparative study 4.7% Terbukti bahwa Pariet 20mg dosis standard sekali sehari lebih superior dibandingkan PPI lain dengan dosis tinggi Holtman G. Pada HARI 1 Keluhan heartburn BERAT dan SANGAT BERAT pada pasien GERD diperbaiki.Dengan Pariet 20mg sekali sehari…….7% 2 HARI 1 – CEPAT BEBASKAN KELUHAN PADA KASUS BERAT & SANGAT BERAT 4.

et al.. ≈ 80% 1 pasien GERD mendapat perbaikan keluhan heartburn SIANG dan MALAM hari pada HARI 1 Robinson M. 16: 445-454 . open-label assessment of patients with erosive oesophagitis. Aliment Pharmacol Ther 2002.HARI 1 – CEPAT BEBASKAN KELUHAN SIANG & MALAM HARI Dengan Pariet 20mg sekali sehari……. Onset of symptom relief with rabeprazole: a community-based.

meskipun dosisnya sudah ditingkatkan menjadi dosis tinggi. Onset of symptom relief with rabeprazole: a community-based. 1 Robinson M. 16: 445-454 . Dari 502 pasien tersebut mendapatkan pengobatan dengan Pariet 20mg dengan dosis sekali sehari menunjukkan: Lebih dari 50% terbebas dari keluhan heartburn pada hari 1 Dan pengobatan dilanjutkan samapai dengan minggu ke 4. Aliment Pharmacol Ther 2002. open-label assessment of patients with erosive oesophagitis.. Pada HARI 1 pasien terbebas dari keluhan heartburn SIANG dan MALAM hari Sejumlah 502 dari 2579 pasien GERD dilaporkan telah mendapatkan pengobatan dengan Lansoprazole atau Omeprazole tetapi gagal.. HARI 1 – CEPAT BEBASKAN KELUHAN JIKA GAGAL DENGAN PPI LAIN Dengan Pariet 20mg sekali sehari……. et al.Jika dengan PPI lain sudah tidak efektif…. terbukti lebih dari 80% terbebas dari keluhan. meskipun sudah ditingkatkan dosisnya….

Eur J Pharmacol 2006. Pariet 20mg sekali sehari mempertahankan pH optimal >3 dan pH > 4 lebih lama dibandingkan Esomeprazole 40mg HARI 1 Hal ini ditunjukkan dari persentase rata – rata lamanya mempertahankan pH >3 dan pH > 4 pada kelompok yang mendapatkan pengobatan dengan Pariet 20mg sekali sehari lebih tinggi secara nyata dibanding Esomeprazole 40mg Catatan: pH optimal adalah pH ideal yang dibutuhkan untuk pengobatan penyakit akibat asam lambung Ulkus : pH dipertahankan > 3 GERD : pH dipertahankan > 4 4 Warrington S. et al.HARI 1 – CEPAT MENGENDALIKAN pH OPTIMAL Pada Secara nyata. Effects of single doses of rabeprazole 20mg and esomeprazole 40mg on 24-h intragastric pH in healthy subjects. 62: 685-691 .

double-blind. comparative study of standard-dose rabeprazole and highdose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002. et al. 16: 479-485 .CEPAT SEMBUH 84% pasien GERD derajat menunjukkan kesembuhan secara endoskopis dengan pengobatan Pariet III pada minggu ke 20mg sekali sehari 4 Dosis standard Pariet 20mg setara dengan dosis tinggi Omeprazole 40 dalam menyembuhkan lesi 2 Holtman G. A randomized.