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A. GERD is one of the least common conditions affecting the GI system. B. All GERD patients will require medication to control their symptoms. C. + 50% of adults experience reflux at least once a month. D. GERD symptoms generally occur before meals.
GERD
Pathophysiology
Simple Plumbing Circuit Esophagus: Antegrade pump LES: Valve Stomach: Reservoir
Hiatal Hernia
Clinical Presentation
Classic GERD Extraesophageal/Atypical GERD Complicated GERD
Classical Symptoms
Extraesophageal Manifestations
Pulmonary Asthma Aspiration pneumonia Chronic bronchitis Pulmonary fibrosis Other Chest pain Dental erosion ENT Hoarseness Laryngitis Pharyngitis Chronic cough Globus sensation Dysphonia Sinusitis Subglottic stenosis Laryngeal cancer
Extraesophageal Pathophysiology
Complicated Symptoms
Dysphagia: Difficulty swallowing Food sticks or hangs up Odynophagia Retrosternal pain with swallowing Bleeding
ALARM SYMPTOMS!!!
Systemic signs: Fevers/Chills/Nightsweats Weight loss Abdominal pain Upper/Lower GI Bleeding Syncope Shortness of Breath/Chest Pain Dysphagia Hoarseness
Diagnostic Tests
Barium esophagogram Esophagogastroduodenoscopy Esophageal manometry Ambulatory 24-hour pH monitoring
Treatment Goals
Eliminate symptoms Heal esophagitis Manage or prevent complications Maintain remission
Treatment Effectiveness
Treatment
Lifestyle modifications/antacids
Response
20%
H2-receptor antagonists
Single-dose PPI Increased-dose PPI
50%
80% Up to 100%
Lifestyle Modifications
Elevate head of bed 4-6 inches Avoid eating within 2-3 hours of bedtime Lose weight if overweight Stop smoking Modify diet
Frequent but smaller meals Avoid fatty/fried food, peppermint, chocolate, alcohol, carbonated beverages, coffee & tea
GERD Chronic Relapsing Condition Esophagitis relapses quickly after cessation of therapy > 50 % relapse within 2 months > 80 % relapse within 6 months Effective maintenance therapy is imperative
Complications
Erosive/ulcerative esophagitis
Esophageal stricture
Barretts esophagus
Adenocarcinoma
When To Do Surgery?
Intractable GERD Rare Difficult to manage strictures Severe bleeding from esophagitis Non-healing ulcers Requiring long-term PPI-BID in a healthy young patient Persistent regurgitation/aspiration symptoms Not Barretts esophagus alone
Open Label, Multicentre, 8 weeks study in 2499 patients Patient with satisfactory Day-time or Night-time Symptom Relief
80%
Robinson M, et al. Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis. Aliment Pharmacol Ther 2002; 16: 445-454
Holtman G, et al. A randomized, double-blind, comparative study of standard-dose rabeprazole and highdose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002; 16: 479-485
A randomized, double-blind study for 8 weeks (n=230) in patients with GERD; sub analysis of Grade III population (n=45)
*p = ns **p = ns
Holtman G, et al. A randomized, double-blind, comparative study of standard-dose rabeprazole and highdose omeprazole in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2002; 16: 479-485
Of the total study population, a subset (n=502) reported ineffective relief with prior use of either Lansoprazole or Omeprazole
Robinson M, et al. Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis. Aliment Pharmacol Ther 2002; 16: 445-454
Median 24-hour pH monitoring in a Crossover Study A Cross-Over, Double Blind, Randomized Study of H. Pylorinegative subjects (n=18). Result of post-dose (08.30-08.00 h)
*p < 0.03
Pantoflickova D, et al. Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors. Aliment Pharmacol Ther 2003; 17: 1507-1514
Open, Randomised, 2-way crossover, Clinical pharmacology study in H. Pylori-negative healthy volunteers n=24: 14-24 hours post-dose (Sub-analysis during night-time period)
*p < 0.05 Warrington S, et al. Effects of single doses of rabeprazole 20mg and esomeprazole 40mg on 24h intragastric pH in healthy subjects. Eur J Pharmacol 2006; 62: 685-691
A randomized, Double-Blind, Double-Dummy, 2-way crossover study of H. Pylorinegative volunteers (n=33). 95% confidence intervals are represented by vertical lines
*p < 0.05 Armstrong D, et al. Oral rabeprazole vs intravenous pantoprazole: a comparison the effect on intragastric pH in healthy subjects. Aliment Pharmacol Ther 2006; 25: 185-196
Rabeprazole has the fastest onset of action compared with other PPIs
Every PPI requires acidic environment to be converted into their active forms Rabeprazole remains activated rapidly even in high pH
Chemical Activation Half-Life
pH: 1.2
pH: 5.1
1. Pantoflickova D, et al. Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors. Aliment Pharmacol Ther 2003; 17: 1507-1514 2. Kromer W et al. Differences in pH-Dependent Activation Rates of Substituted Benzimidazoles and Biological in vitro Correlates. Pharmacology 1998; 56: 57-70
Fock KM, et al. Rabeprazole vs esomeprazole in non-erosive gastro-esophageal reflux disease: A randomized, double-blind study in urban Asia. World J Gastroenterol 2005; 11(20): 3091-3098
1. Bour B, et al. On-demand maintenance therapy with rabeprazole (RAB) 10mg an effective alternative to continous therapy for patients with frequent gastroesophageal reflux symptomatic relapse. Gastroenterology 2003; 124(4(suppl 1)): A 219 S 161 2. Bytzer P, et al. Six-month trial of on-demand rabeprazole 10mg maintains symptom relief in patients with non-erosive reflux disease. Aliment Pharmacol Ther 2004; 20: 181-188
Sediaan Pariet 10mg Pariet 20mg Prosogan 30mg Nexium 20mg Nexium 40mg Pantozol 20mg Pantozol 40 mg OMZ 20mg Lancid 30mg Pumpitor 20mg
Harga per tablet (HNA) 12,292 14,216 14,321 12,227 14,927 11,100 13,900 11,000 10,750 10,560
Biaya PPI untuk pengobatan 417,928 483,344 801,990 684,720 835,920 621,600 778,400 616,000 602,000 591,360
Index
Selisih Biaya 65,416 384,062 266,792 417,992 203,672 360,472 198,072 184,072 173,432
The one & only approved 7-day treatment for H. pylori infections
Times needed for H. pylori eradication using combination therapy
Chey WD, Wong BCY. American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection. Am J Gastroenterol 2007;102:18081825
Sediaan
Harga per tablet (HNA) 14,216 14,321 14,927 19,782 11,000 10,750 10,560
Biaya PPI untuk pengobatan 99,512 200,498 149,271 197,820 110,000 150,500 105,600
Index
Selisih Biaya
Pariet 20mg Prosogan 30mg Nexium 40mg Losec 20mg OMZ 20mg Lancid 30mg Pumpitor 20mg
101% 100,986 50% 99% 11% 51% 6% 49,759 98,308 10,488 50,988 6,088
Interaksi obat antara PPI dengan obat-obatan yang berhubungan dengan penghambatan cytochrome P450
1-8
Rabeprazole
Pantoprazole
Warfarin
Omeprazole
Warfarin
Phenytoin
Diazepam
Disulfiram
Lansoprazole
Warfarin
Phenytoin
Diazepam
Digoxin
Theophylline
Tacrolimus
Esomeprazole
Warfarin
Phenytoin
Diazepam
Citalopram
Clomipramin
Imipramin
1. Robinson M, et al. Drugs 2003;63:2739-54. 2. Ishizaki T et al. Aliment Pharmacol Ther 1999;13(Suppl.3):27-36. 3. Fuhr U, et al. Pharmazie 57(2002)9. 4. Giannini EG, et al. Dig Dis Sci 2006;51:1602-6. 5. Takahashi K, et al. Drug Metab Pharmacokinet 2007;22:441-4. 6. Hosohata K, et al. Drug Metab Pharmacokinet 2008;23:134-8. 7. Lim PWY, et al. Journal of Gastroenterology and Hepatology (2005)20:522-28. 8. Pariet SmPC 2008 Losec SmPC, Pantozol SmPC, Prosogan FD SmPC. Nexium SmPC 2008