DRUGS FOR GERD

AND PEPTIC ULCER

DISEASE (PUD)
MODULE 6 - LESSON 1
Gastroesophageal Reflux
Disease (GERD)
◦ a condition that develops when
the reflux of stomach contents
causes troublesome symptoms
and/or complications
◦ Primary symptom: Heartburn
◦ Heartburn: burning retrosternal
pain radiating upward due to
exposure of the esophagus to
acid
Factors that precipitate GERD
 PHYSIOLOGIC:
◦ Reduced salivary bicarbonate
◦ impairs neutralisation of gastric acid (may be caused by reduced secretion
or impaired peristalsis and reduced saliva transport)
◦ Impaired mucosal defence/acid clearance in the esophagus
◦ Increased reflux of acid from the stomach due to impaired pressure
at the lower esophageal sphincter,
 LIFESTYLE FACTORS
 Smoking
 alcohol intake
 fat intake and
 obesity
GERD treatment options
Lifestyle Antacids and
modifications alginates

PPIs Approaches H2RAs

Prokinetic Surgery
motility agents

Hatlebakk & Berstad, Clin Pharmacokinet 1996; 31: 386–406.

 Lifestyle modifications for the
management of GERD
Reduce weight

Stop smoking Elevate head

of bed

Modifications
Avoid reflux-promoting
agents (e.g. alcohol, Consider
coffee, some foods) alternatives to
(not evidence based) reflux-promoting drugs
(e.g. theophylline,
anticholinergics)
Eat small meals,
no late meals,
reduce fat
Antacids
Increase the pH of gastric refluxate
 Reduce the erosive effect and hence reduce symptoms
Suitable for quick relief of mild symptoms
Most antacids are not suitable therapies for established
GERD or esophagitis
 Less effective than H2RAs or PPIs for treatment of GERD
Adverse effects include:
 Accumulation in patients with renal impairment
 Constipation
 Diarrhea
Prokinetic motility agents
Increase LES pressure and enhance gastric
emptying
Relieve heartburn but do not heal esophagitis
Cisapride, Tegaserod were used in GERD
treatment in the past
 The risk of cardiac side effects with both now
excludes these agents from use in GERD

Domperidone, Itopride, Mosapride

 H2-receptor antagonists
(H2RAs)
Inhibit histamine stimulation of gastric parietal
cell, resulting in reduced gastric acid secretion
Slower onset but longer duration of action
than antacids
Cimetidine is associated with more drug
interactions than other H2RAs, such as ranitidine
H2RAs are generally not as effective as PPIs for
symptom relief or healing

de Caestecker, BMJ 2001; 323: 736–9.

Sonnenberg, Pharmacoeconomics 2000; 17: 391–401.
 PROTON PUMP INHIBITORS
(PPIs)
◦ Antisecreting agents
◦ completely inhibit acid secretion of parietal cells (acid-secreting cells
in the stomach)
◦ Examples of common proton-pump inhibitors include:
◦ Omeprazole
◦ Esomeprazole
◦ Lansoprazole
◦ Pantoprazole
◦ Rabeprazole
 PROTON PUMP INHIBITORS (PPIs) :
Mechanism of Action
◦ Proton-pump inhibitors reduce stomach acid production through
irreversible inhibition of the proton pump – the H+/K+-ATPase, a pump
present in gastric parietal cells
PPIs are used in the treatment
of the following conditions:
◦ Peptic ulcer disease
◦ NSAID-associated ulcers
◦ Dyspepsia
◦ Gastroesophageal reflux disease (GERD)
◦ Barrett’s esophagus
◦ Elimination of Helicobacter pylori infection
◦ proton-pump inhibitors are used in combination with other drugs,
such as antibacterial drugs
PEPTIC ULCER DISEASE (PUD)
◦ CAUSES:
◦ Helicobacter pylori (H. pylori) infection
◦ Is present in ~60% of gastric ulcer and 70% of duodenal ulcer patients
◦ Regular use of NSAIDS
◦ Hypersecretion, hypergastrinemia
◦ Alcohol, smoking and/or stress
◦ Major aggressive and defensive factors in peptic ulcer disease:

Aggressive factors Defensive factors

HCl Mucosal epithelium
pepsin mucus
ulcerogenic agents Bicarbonate
H.pylori Mucosal blood flow

*There should always be a balance between these two groups of factors

Ulcer disease and H. pylori

◦ H. pylori infection can cause inflammation in both the stomach

and the duodenum

◦ H. pylori infection can produce the differing patterns of gastritis

with gastric and duodenal ulcers
 Gastric vs Duodenal ulcer
Gastric ulcer Duodenal ulcer
◦ Gastric ulcers are ◦ Most duodenal ulcers occur
uncommon before 40 years between 25
of age and 55 years
◦ Pain often increased by ◦ Pain temporarily relieved by
food intake, relieved by food intake and antacids,
fasting pain is often nocturnal
◦ Acid secretion normal ◦ Acid hypersecretion
◦ Weight loss possible ◦ No weight loss
◦ *Hematemesis may occur ◦ Melena may occur
* Vomiting of blood *dark sticky feces containing partly digested blood
 Treatment goals in PUD
Pain relief and resolution of other
symptoms
Mucosal healing
Prevention of recurrence
Prevention of complications
Most frequently used agents in
anti-H. pylori regimens
oPPIs
oRanitidine bismuth citrate (RBC)
oAmoxicillin
oMacrolides (e.g. clarithromycin)
oNitroimidazoles (e.g. metronidazole)
oTetracycline
oBismuth

Gisbert et al., Curr Opin Gastroenterol 2001; 17(Suppl 1): S47–54.

 Management of NSAID-induced
peptic ulcer disease
 Discontinue use of NSAIDs or substitute with less toxic
agents
 Low-toxicity NSAIDs or COX-2 inhibitors
 Suppress acid secretion
 Normal-dose PPI therapy
 High-dose H2RA therapy
 Use mucosal protectants
 Misoprostol – prostaglandin analogue (substantial side-
effects, abortifacient)
 Rebamipide
 Acid suppression in
NSAID-induced peptic ulcer
◦ Antacids
 Limited efficacy, especially in preventing gastric
ulcer

◦ H2RAs
 Effective in preventing gastric ulcer;
some drug interactions, well tolerated

◦ PPIs
 More effective than H2RAs for healing NSAID-
induced ulcers, well tolerated
TREATMENT OF NSAID-INDUCED PEPTIC
ULCER
◦ Anti secretory agents (PPI’s)
◦ DU: 4 – 6 weeks
◦ GU: 6 – 8 weeks

◦ H. pylori eradication

◦ Remove offending agents (e.g. NSAIDs)

Treatment summary for peptic
ulcer: key points
H. pylori eradication is essential in H. pylori-
positive patients
NSAIDs should be discontinued or reduced, if
possible
PPIs are the most effective agents for acid
suppression and the most appropriate first-line
therapy
LEARNING TASK
◦ Compare and contrast the various drugs used in treating GERD
and PUD
DRUG CLASS ADVANTAGES (in DISADVANTAGES
pharmacological (Risks/SE/ADRs/DI)
terms)
Proton pump
inhibitors
H2-R antagonists
Antacids
Cytoprotective
Drugs
• Misoprostol
• Rebamipide
• Sucralfate