DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1318
Severity of GERD
Stage I
Sporadic uncomplicated heartburn, often
in setting of known precipitating factor.
Often not the chief complaint.
Less than 2-3 episodes per week.
No additional symptoms.
Medical Management
Lifestyle modification, including diet,
positional changes, weight loss, etc.
Antacids and/or histamine H 2 receptor
antagonists as needed.
Stage II
Frequent symptoms, with or without
esophagitis.
Greater than 2-3 episodes per week.
Proton pump inhibitors more effective
than histamine H 2 receptor antagonists.
SECTION VI
Stage III
Chronic, unrelenting symptoms;
immediate relapse off therapy.
Esophageal complications (e.g.,
stricture, Barrett’s metaplasia).
Proton pump inhibitor either once or
twice daily.
Figure 45–5. General guidelines for the medical management of gastroesophageal reflux disease (GERD). Only medications that suppress
acid production or that neutralize acid are shown. (Adapted from Wolfe and Sachs, 2000, with permission from Elsevier.
Copyright © Elsevier.)
DRUGS AFFECTING GASTROINTESTINAL FUNCTION
twice-daily dosing usually is required. Antacids are recommended
only for the patient with mild, infrequent episodes of heartburn. In
general, prokinetic agents (Chapter 46) are not particularly useful
for GERD, either alone or in combination with acid-suppressant
medications.
GERD is a chronic disorder that requires long-term therapy.
Some experts advocate “stepdown” approaches that attempt to maintain
symptomatic remission by either decreasing the dose of the
Table 45–3
Antisecretory Drug Regimens for Treatment and
Maintenance of GERD
DRUG
DOSAGE
H 2
Receptor Antagonists
Cimetidine
400 * /800 * mg bid
Famotidine
20/40 mg bid
Nizatidine
150 * /300 * mg bid
Ranitidine
150/300 mg bid
Proton Pump Inhibitors
Esomeprazole
Lansoprazole
Omeprazole
Pantoprazole
Rabeprazole
bid, twice daily.
*
Indicates unlabeled use.
20/40 mg daily/40 * mg bid
30 * /60 * mg daily/30 * mg bid
20/40 * mg daily/20 * mg bid
40/80 * mg daily/40 * mg bid
20/40 * mg daily/20 * mg bid
proton pump inhibitor or switching to an H 2
receptor antagonist.
Other experts have advocated intermittent, “on-demand” therapy
with proton pump inhibitors for symptomatic relief in patients who
have responded initially but continue to have symptoms. However,
many patients will maintain their requirement for proton pump
inhibitors, and several studies suggest that these drugs are better
than H 2
receptor antagonists for maintaining remission in GERD.
Severe Symptoms and Nocturnal Acid Breakthrough. In patients
with severe symptoms or extraintestinal manifestations of GERD,
twice-daily dosing with a proton pump inhibitor may be needed.
However, it is difficult if not impossible to render patients achlorhydric—even
on twice-daily doses of proton pump inhibitors—and twothirds
or more of subjects will continue to make acid, particularly at
night. This phenomenon, called nocturnal acid breakthrough, has been
invoked as a cause of refractory symptoms in some patients with
GERD. However, decreases in gastric pH at night while on therapy
generally are not associated with acid reflux into the esophagus, and
the rationale for suppressing nocturnal acid secretion (even if feasible)
remains to be established. Nevertheless, patients with continuing
symptoms on twice-daily proton pump inhibitors are often treated by
adding an H 2
receptor antagonist at night. Although this can further
suppress acid production, the effect is short lived, probably due to the
development of tolerance, as described earlier (Fackler et al., 2002).
Therapy for Extraintestinal Manifestations of GERD. With varying
levels of evidence, acid reflux has been implicated in a variety of
atypical symptoms, including noncardiac chest pain, asthma, laryngitis,
chronic cough, and other ear, nose, and throat conditions.
Proton pump inhibitors have been used with some success in certain
patients with these disorders, generally in higher doses and for longer
periods of time than those used for patients with more classic symptoms
of GERD.