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Gastroesophageal Reflux Disease
Toward Better Acid Suppression—Why Do We Need It?
a report by
Carmelo Scarpignato, MD, DSc, PharmD, FRCP, FCP, FACG
Secretary General, World Organization for Specialized Studies on Diseases of the Esophagus
The Need for Better Acid Suppression contribute to the development of erosive esophagitis.
6
Up to 79% of
Acid-suppression therapy with proton pump inhibitors (PPIs) is associated patients with GERD experience nocturnal symptoms associated with their
with well-established benefits in the management of gastroesophageal condition, and improvement in nocturnal symptoms associated with
reflux disease (GERD) and other acid-related disorders. The dramatic reduction in gastric acidity by PPIs is well documented.
7
However, the
success of pharmacological acid suppression in healing ulcers and clinical importance of specifically reducing NAB is controversial. In
managing patients with GERD has been reflected in the virtual abolition patients with GERD, recovery of nocturnal gastric acid secretion is of little
of elective surgery for ulcer disease,
1
a reduction in non-steroidal anti- importance if it is not accompanied by exposure of the esophagus to
inflammatory drugs (NSAID)-associated gastropathy,
2
and the decision by acid. However, patients with severe forms of chronic GERD, and
most patients with reflux symptoms to continue medical therapy rather especially those with Barrett’s esophagus, are more likely to have acid
than undergo surgical intervention. However, a number of challenges reflux during NAB.
5
A recent report
8
has shown that >70% of patients
remain in the management of acid-related disorders. These include had improved night-time symptoms after addition of an H
2
-receptor
management of patients with gastroesophageal symptoms who do not antagonist (H
2
RA) to a twice-daily PPI regimen, thus emphasizing the
respond adequately to PPI therapy, optimal treatment and prevention of clinical impact of controlling NAB.
NSAID-related gastrointestinal (GI) injury, best combination of
antisecretory and antibiotic therapy for the eradication of Helicobacter The administration of current delayed-release (DR) PPIs is recommended 30
pylori infection, and treatment of patients with non-variceal upper GI minutes to one hour prior to a meal in order to ensure that proton pumps
bleeding.
3,4
Indeed, despite their clinical efficacy, when given once daily are activated in the parietal cell at a time when drugs are available in
the currently available PPIs may not adequately control intragastric acidity plasma.
9
Since PPIs all have similar plasma half-lives of one to two hours, any
during the night in a significant proportion of both healthy subjects and proton pump synthesized after drug levels fall will not be blocked from
GERD patients, in whom symptom relief remains suboptimal.
5
In secreting acid. As a consequence, their failure to provide extended
particular, nocturnal acid breakthrough (NAB) continues to be a antisecretory activity depends on their short half-life and speed of
significant issue and, in addition to giving rise to symptoms, may also disassociation from the proton pump, together with the activation or
synthesis of the pumps.
10
The clinical efficacy of the PPIs is related to the
degree of acid suppression.
11
Consequently, PPIs with a longer half-life
Carmelo Scarpignato, MD, DSc, PharmD, FRCP, FCP, FACG, is
resulting in extended acid suppression would be expected to offer improved
Secretary General of the World Organization for Specialized
Studies on Diseases of the Esophagus (OESO), Professor of
clinical efficacy.
10
Pharmacology and Therapeutics at the University of Parma
Medical School, and Associate Professor of Gastroenterology at
Although PPIs have a number of shortcomings that stem from their
the University of Nantes. He is also Consultant Clinical
Pharmacologist at Maggiore University Hospital in Parma. He
pharmacology,
12
there is increasing evidence of both inappropriate
has been Visiting Professor at various prestigious European and prescription and inappropriate use of these drugs. Indeed, a growing
US universities. Professor Scarpignato’s main research interests
number of patients have poor indications to acid suppression. Not
focus on digestive clinical pharmacology, gastrointestinal (GI) motility, and upper GI
pathophysiology. He has published more than 200 peer-reviewed papers on these topics and has
uncommonly, empirical therapy in non-explored and functional dyspepsia is
also edited several books on the clinical evaluation of GI function and the pharmacology and based on PPI therapy at a standard or high dose for two to four weeks. If
therapeutics of digestive diseases. He is or has been on the editorial boards of Pharmacology, Gut,
symptom resolution is limited and patient dissatisfaction continues, the
Digestion, Digestive Diseases, Current Gastroenterology Reports, BMC Gastroenterology, and
Hepatogastroenterology, among others. He is also a Section Editor (GI and liver pharmacology) for
dose is often doubled. Upon sudden arrest of such therapy because of
Fundamental and Clinical Pharmacology and Gastroenterology International, and Co-Editor of two insufficient symptom relief, rebound acid secretion may reactivate GERD-
prestigious book series: Frontiers of Gastrointestinal Research and Progress in Basic and Clinical
like/dyspeptic symptoms, leading to a vicious circle.
3
There is a staggering
Pharmacology. Professor Scarpignato is a Fellow of the Royal College of Physicians (RCP), the
American College of Clinical Pharmacology (ACCP), and the American College of
lack of clear instructions in practice concerning empirical therapy. That PPIs
Gastroenterology (ACG). In addition, he is a member of several national and international are often taken inappropriately is revealed by a US survey
13
showing that
scientific societies, including the British Pharmacological Society (BPS), the American
only 27% of GERD patients dosed their PPI correctly (i.e. up to 60 minutes
Gastroenterological Association (AGA), and the American Society for Pharmacology and
Experimental Therapeutics (ASFET). Professor Scarpignato graduated in biochemistry from the
before any meal of the day) and only 9.7% dosed it optimally (i.e. 15–60
University of Messina, and in medicine and surgery from the University of Modena in Italy. minutes before the first meal of the day). Furthermore, in a study of 1,046
E:
scarpi@tin.it
primary care physicians across the US,
14
only 36% of them gave their
patients advice on when and how to take their medication.
70 © TOUCH BRIEFINGS 2007
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