DRUGS USED TO TREAT PEPTIC ULCER DISEASE AND
GASTROESOPHAGEAL REFLUX DISEASE
The secretion of gastric acid occurs at the level of parietal cells of the oxyntic
gland in the gastric mucosa producing 2-3 liters of gastric juice per day, pH 1 in
hydrochloric acid. Ultimately, this secretory process occurs via an H+/K+-ATPase
that exchanges hydronium ion (H3O+) with uptake of a potassium ion.
Several mediators regulate this secretion by way of receptor systems on the
basolateral membrane. The H2 histaminergic pathway is cAMP dependent.
Gastrin and muscarinic receptors also regulate the secretion of gastric acid
through calcium ion dependent pathways.
In parietal cells, E series prostaglandins work in opposition to the histaminergic
pathway, inhibiting histamine-stimulated adenylate cyclase activity. Other
epithelial cells in the mucosal lining under the influence of prostaglandin
mediated pathways secrete bicarbonate and mucus, both of which are
important in protecting the gastric lining from the effects of acid secretion.
Several major causative factors are recognized: infection with gram negative
Helicobacter pylori, use of nonsteroidal anti-inflammatory drugs (NSAIDs),
increased hydrochloric acid secretion, inadequate mucosal defense against
gastric acid. Treatment approaches include:
1) Eradicating the H. pylori infection,
2) Reducing secretion of gastric acid with the use of PPIs or H2-receptor
antagonists, and/or
3) Providing agents that protect the gastric mucosa from damage, such as
misoprostol and sucralfate.
4) If patients are unable to tolerate the above therapies, neutralizing gastric acid
58
, with non-absorbable antacids is an option.
Mechanism of HCl formation in stomach
59
GASTROESOPHAGEAL REFLUX DISEASE
The secretion of gastric acid occurs at the level of parietal cells of the oxyntic
gland in the gastric mucosa producing 2-3 liters of gastric juice per day, pH 1 in
hydrochloric acid. Ultimately, this secretory process occurs via an H+/K+-ATPase
that exchanges hydronium ion (H3O+) with uptake of a potassium ion.
Several mediators regulate this secretion by way of receptor systems on the
basolateral membrane. The H2 histaminergic pathway is cAMP dependent.
Gastrin and muscarinic receptors also regulate the secretion of gastric acid
through calcium ion dependent pathways.
In parietal cells, E series prostaglandins work in opposition to the histaminergic
pathway, inhibiting histamine-stimulated adenylate cyclase activity. Other
epithelial cells in the mucosal lining under the influence of prostaglandin
mediated pathways secrete bicarbonate and mucus, both of which are
important in protecting the gastric lining from the effects of acid secretion.
Several major causative factors are recognized: infection with gram negative
Helicobacter pylori, use of nonsteroidal anti-inflammatory drugs (NSAIDs),
increased hydrochloric acid secretion, inadequate mucosal defense against
gastric acid. Treatment approaches include:
1) Eradicating the H. pylori infection,
2) Reducing secretion of gastric acid with the use of PPIs or H2-receptor
antagonists, and/or
3) Providing agents that protect the gastric mucosa from damage, such as
misoprostol and sucralfate.
4) If patients are unable to tolerate the above therapies, neutralizing gastric acid
58
, with non-absorbable antacids is an option.
Mechanism of HCl formation in stomach
59
