Pathophysiologic mechanisms : Transient lower esophageal sphincter relaxations (tLESRs) A hypotensive lower esophageal sphincter (LES) Anatomic disruption

of the gastro esophageal junction, often associated with a hiatal hernia

Heart burn and regurgitation are The most common symptoms

How the Heartburn recognised?

Gastro-esophageal Refluks Disease (GERD)

Esophageal syndromes Symptomati c syndromes 1. Typical refluks syndrome 2. Refluks chest pain syndrome Syndromes with Esophageal injury Extra-Esophageal syndromes Established association Proposed Association

1. Pharyngitis 1. Refluks esophagitis 1. Refluks cough syndrome 2. Sinusitis 2. Refluks stricture 3. Barrets esophagus 2. Refluks laryngitis 3. Idiopathic syndrome Pulmonary fibrosis 4. Esophageal 4. Recurrent otitis Adenocarcinoma 3. Refluks astma syndrome media 4. Refluks dental erosion syndrome (Vakil etal., Am J Gastroenterol 2006; 101:1900-1920)



Progressive dysphagia Odynophagia Weight loss (unintentional) Anemia (new onset) Hematemesis and/or melena Family history of gastric and/or esophageal cancer Chronic non-steroid anti-inflammatory drug use Age >40 years in areas of a high prevalence of gastric cancer

esofagitis

esofagitis

normal

Question

Frequency score (point) for symptome

0 day 1 day 1 1 2-3 day 2 2 4-7 day 3 3 0 0

1. How often did you have a burning feeling behind your breastbone (heartburn) ? 2. How did you have a stomach contents (liquid or food) moving upward tu your throat or mouth (regurgutation) ? 3. How often did you have a pain in the center of the upper stomach? 4. How often did you have nausea? 5. How often did you difficulty getting a good nights sleep because of your heartburn and/or your regurgutation ? 6. How often did you take additional medication for your heartburn and/or regurgutation? (such as Tums, Rolaids, Maalox?)

3 3 0

2 2 1

1 1 2

0 0 3

Alarm features present

Alarm features absent PPI therapy 4 week and Review at 2 to 4 week

REFER for EGD or H.pylori test Stop PPI at least 1 week

Symptomes persist

Symptomes respond Trial for Stop PPI Relapse

Frequent relapse, or Alarm features

On-demand therapy

Restart PPI

... and step down dosing

Conclusion: -On-demand therapy is a useful option in GERD but needs to be limited to selected patients -Severe Grade of esophagitis and Barrets esophagus are best managed with continuous therapy (Gjostedt et al. Aliment Pharmacol Ther 2005. 22: 183-91)

Patophysiologi of gastric-doodenal mucosa injury

Hp associated ulcer and cancer

NSAIDs associated ulcer and gastric erosion



Alterations in gastric mucosal barrier Prostaglandin synthesis Mucus and bicarbonate secretion Submucosal blood flow Mucosal ATP Cell turnover Platelet function (irreversible)

Ivey KJ. Am J Med. 1988;84:41-48.

Ulkus antrum

Ulkus duodenum

gastropathy

Number of deaths 25,000 20,000

1997 US mortality data for seven selected disorders

The silent epidemic

16500

15,000 10,000 5000 0 NSAID

Singh G et al G. Epidemiology of NSAID-induced GI complications. J Rheumatol 1999;26:Sup 26:18-24.

Wolfe et al Gastrointestinal Toxicity of Nonsteroidal Antiinflammatory Drugs. NEJM 1999; 340: 1888-99.

Hospitalisations/1000 person-years 25 20 15 10 5 0 20 30 40 50 60 70 80

female users male users

male non-users female non-users

Age (years)

List of Available NSAIDs: Prescription & OTC

* List

* of trade names is not exhaustive

NON-SALICYLATES
Diclofenac (Voltaren) (Celebrex) Diclofenac/Misoprostol (Arthrotec) (Vioxx) Etodolac (Lodine) (Bextra) Fenoprofen (Nalfon) Flurbiprofen (Ansaid) Ibuprofen a,b,c (Motrin, Advil) Indomethacin (Indocin) Ketoprofen a,b,c(Orudis) Ketorolac (Toradol)c Meclofenamate Mefenamic acid (Ponstel) Meloxicam (Mobic) Nabumetone (Relafen) Naproxen a,b,c(Naprosyn, Anaprox) Oxaprozin (Daypro) Piroxicam (Feldene) Sulindac (Clinoril) Tolmetin (Tolectin)

SALICYLATES
Aspirin a,c (Zorprin, Easprin) Diflunisal (Dolobid) Salsalate (Disalcid, Salflex)

COX-2 INHIBITORS
Celecoxib Rofecoxib Valdecoxib

Choline salicylate (Trilisate) Magnesium salicylate (Magan)

Comments on Over-the-Counter Preparations:

a

Also available as OTC preparations in U.S. b OTC dose is usually half of prescribed dose C All OTC NSAIDs are non-selective COX Inhibitors



PPI (omeprazole 20-40mg 1x1/d) > PGE1, Misoprostol (cytotec 200 g 1x3/d) > H2 receptor antagonist (famotidine 40mg 1x2/d or ranitidine 300 mg 1x2/d) Misoprostol good for prevention of gastric ulcer but causes diarrhea

Algoritm of dyspeptic patients

 Diagnosis and outcome assessment by

urea breath test (off PPIs) if endoscopy not required. Serology least sensitive and specific Therapy should be according to best practice, not ad hoc combinations If first line failure, dont retreat with the same combination- use proven 2nd line Rx Consider PPI prophylaxis selectively

Standard PPI based triple therapy : 7-14 days PPI, amoxicillin 1 g, clarithromycin 500 mg twice daily PPI, metronidazole 400 mg, clarithromycin 500 mg twice daily PPI, amoxicillin 1 g, metronidazole 400 mg twice daily 1 line therapy in Quadriple therapy: 714 days Asia PPI twice daily, bismuth 240 mg twice daily, metronidazole 400 mg twice daily or three times daily, tetracycline 500 mg four times daily Levofloxacin-based triple therapy: 10 days PPI, levofloxacin 250 mg (or 500 mg), amoxicillin 1 g twice daily Rifabutin-based triple therapy: 710 days PPI, rifabutin 150 mg, amoxicillin 1 g twice daily
st

Fock KM, et al. Journal of Gastroenterology and Hepatology 24 (2009) 15871600

Low NSAID gut risk

High NSAID gut risk Consider non-NSAID therapy or Non-selective NSAID + PPI or COX-II NSAID (PPI) or

Low CV risk (No aspirin)

Consider non-NSAID therapy Non-selective NSAID

H. pylori test and treat

High CV risk Consider non-NSAID therapy Consider non-NSAID therapy or Non-selective NSAID (naproxen) PPI or Non-selective NSAID + PPI or Avoid NSAIDs

(On aspirin)

Adapted from Fendrick. Am J Manag Care 2004; 10: 740-741 and Sung JGH 2010; 25: 229-33

H.pylori : the Maastricht III Consensus Report

Recommendations PU (active or inactive) including past bleeding: eradicate H pylori (includes prior to NSAID use) In nave users of NSAIDs (without prior PU), H pylori eradication may prevent peptic ulcer and or bleeding Chronic NSAID users: H pylori eradication of value but is insufficient to prevent NSAID related ulcers completely Long term NSAID users with PU and/or ulcer bleeding, PPI maintenance is better than H pylori eradication in preventing ulcer recurrence Level of evidence 1a 1b Grade of recommendation A A

1b

1b

Malfertheiner P et al. Gut 2007; 56: 772-78.

Second AsiaPacific Consensus Guidelines for Helicobacter pylori infection 2009

H. pylori infection should be tested for and eradicated: Prior to long-term aspirin or NSAID therapy in patients at high risk for ulcers and ulcer-related complications To reduce the risk of peptic ulcer and upper gastrointestinal bleeding in NSAID-naive users

Fock KM, et al. Journal of Gastroenterology and Hepatology 24 (2009) 15871600

Feature of Gastric acid secretion