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

GERD and Pregnancy. Heartburn is estimated to occur in 30-50% of
pregnancies, with an incidence approaching 80% in some populations
(Richter, 2003). In the vast majority of cases, GERD ends soon after
delivery and thus does not represent an exacerbation of a preexisting
condition. Nevertheless, because of its high prevalence and the fact
that it can contribute to the nausea of pregnancy, treatment often is
required. Treatment choice in this setting is complicated by the
paucity of data for the most commonly used drugs. In general, most
drugs used to treat GERD fall in FDA Category B, with the exception
of omeprazole (FDA Category C).
Mild cases of GERD during pregnancy should be treated conservatively;
antacids or sucralfate are considered the first-line drugs.
If symptoms persist, H 2
receptor antagonists can be used, with ranitidine
having the most established track record in this setting. PPIs
are reserved for women with intractable symptoms or complicated
reflux disease. In these situations, lansoprazole is considered the preferred
choice among the proton pump inhibitors, based on animal
data and available experience in pregnant women.
PEPTIC ULCER DISEASE
The pathophysiology of peptic ulcer disease is best
viewed as an imbalance between mucosal defense factors
(bicarbonate, mucin, prostaglandin, NO, and other
peptides and growth factors) and injurious factors (acid
and pepsin). On average, patients with duodenal ulcers
produce more acid than do control subjects, particularly
at night (basal secretion). Although patients with gastric
ulcers have normal or even diminished acid production,
ulcers rarely if ever occur in the complete absence of
acid. Presumably, a weakened mucosal defense and
reduced bicarbonate production contribute to the injury
from the relatively lower levels of acid in these patients.
H. pylori and exogenous agents such as NSAIDs interact
in complex ways to cause an ulcer. Up to 60% of
peptic ulcers are associated with H. pylori infection of
the stomach. This infection may lead to impaired production
of somatostatin by D cells and, in time,
decreased inhibition of gastrin production, resulting in
increased acid production and reduced duodenal bicarbonate
production.
NSAIDs also are very frequently associated with peptic
ulcers and bleeding. Topical injury by the luminal presence of the
drug appears to play a minor role in the pathogenesis of these ulcers,
as evidenced by the fact that ulcers can occur with very low doses of
aspirin (10 mg) or with parenteral administration of NSAIDs
(Wallace, 2008). The effects of these drugs are instead mediated systemically;
the critical element is suppression of mucosal
prostaglandin synthesis (particularly PGE 2
and PGI 2
). Most of the
mucosal prostaglandin synthesis occurs via the constitutively
expressed cyclooxygenase-1 (COX-1), but COX-2, which can be
very rapidly induced, also contributes significantly to the generation
of mucosal-protective prostaglandins. Thus suppression of COX-1
and COX-2 by NSAIDs contributes to the induction of mucosal
injury. COX-2-derived prostaglandins are particularly important in
repair of mucosal injury (Wallace, 2008).
Table 45–4 summarizes current recommendations for drug
therapy of gastroduodenal ulcers. Proton pump inhibitors relieve
symptoms of duodenal ulcers and promote healing more rapidly than
do H 2
receptor antagonists, although both classes of drugs are very
effective in this setting. Peptic ulcer represents a chronic disease,
and recurrence within 1 year is expected in the majority of patients who
do not receive prophylactic acid suppression. With the appreciation
Table 45–4
Recommendations for Treatment of Gastroduodenal Ulcers
DRUG ACTIVE ULCER MAINTENANCE THERAPY
H 2
Receptor Antagonists
Cimetidine 800 mg at bedtime/400 mg twice daily 400 mg at bedtime
Famotidine 40 mg at bedtime 20 mg at bedtime
Nizatidine/ranitidine 300 mg after evening meal or at bedtime/150 mg twice daily 150 mg at bedtime
Proton Pump Inhibitors
Lansoprazole
15 mg (DU; NSAID risk reduction) daily
30 mg (GU including NSAID-associated) daily
Omeprazole
20 mg daily
Rabeprazole
20 mg daily
Prostaglandin Analog
Misoprostol
200 μg four times daily (NSAID-associated ulcer prevention)*
DU, duodenal ulcer; GU, gastric ulcer.
*Only misoprostol 800 μg/day has been directly shown to reduce the risk of ulcer complications such as perforation, hemorrhage, or obstruction
(Rostom et al., 2009).