Acid-peptic disease includes peptic ulcer (gastric and duodenal), gastroesophageal reflux and
Zollinger – Ellison syndrome.
Peptic – ulcer disease is thought to result from an imbalance between cell – destructive effects
of hydrochloric acid and pepsin and cell-protective effects of mucus and bicarbonate on the
other side. Pepsin is a proteolyic enzyme activated in gastric acid, also can digest the stomach
wall.
A bacterium, Helicobacter pylori is now accepted to be involved in the pathogenesis of ulcer.
In gastroesophageal reflux, acidic stomach contents enter into the esophagus causing a burning
sensation in the region of the heart; hence the common name heartburn, or other names such
as indigestion, dyspepsia, pyrosis, etc.
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Zollinger-Ellison syndrome is caused a tumor of gastrin secreting cells of pancreas
characterized by excessive secretion of gastrin that stimulates gastric acid secretion.
The disorders can be treated by drugs, which are able to:
- Neutralize gastric acid (HCl) e.g. magnesium hydroxide
- Reduce gastric acid secretione.g. cimetidine
- Enhance mucosal defences e.g sucralfate
- Exert antimicrobial action against H.pylori e.g. clarithromycin
The effective therapeutic approach of ucler is based on the adage:
“no acid, no ulcer”
Anti – ulcer drugs: drugs used in the prevention and treatment of peptic ulcer disease act mainly
to decrease cell-destructive effects, increase cell – protective effects or both.
A: Gastric acid neutralizers (antacids)
Antacids are alkaline substances (weak bases) that neutralize gastric acid (hydrochloric acid)
They react with hydrochloric acid in the stomach to produce neutral or less acidic or poorly
absorbed salts and raise the PH of stomach secretion, and above PH of 4, pepsin is inactive.
Antacids are divided into systemic and nonsystemic
Systemic, e.g. sodium bicarbonate are absorbed into body fluids and may alter acid – base
balance. It can be used in the treatment of metabolic acidosis.
Non systemic, do not alter acid – base balance significantly. They are used as gastric antacids;
and include aluminium, magnesium and calcium compounds e.g. (Al(OH)3, MgS2O3 , Mg(OH)2,
CaCO3)
Gastric antacids differ in their potency, in onset of action, duration of action and adverse
effects produced. - Magnesium compounds have a relatively high neutralizing capacity, rapid onset of action,
cause diarrhoea and hypermagnesemia. - Aluminium compounds generally have a low neutralizing capacity, slow onset of action but
long duration of action and may cause constipation.
Calcium compounds are effective and have a rapid onset of action but may cause
hypersecretion of acid (acid – rebound) and milk-alkali syndrome (hence rarely used in peptic
ulcer disease). All gastric antacids act chemically although some like magnesium trisiolicate can
also act physically.
The most commonly used antacids, are mixtures of aluminium hydroxide and magnesium
hydroxide (e.g. Gelusil, Maalox etc).
Antacids act primarily in the stomach and are used to prevent and treat peptic ulcer. They are
also used in the treatment of Reflux esophagitis and Gastritis
B. Gastric acid secretion inhibitors (antisecretory drugs):
HCl is secreted by parietal cells of the gastric mucosa which contain receptors for acetylcholine,
histamine and gastrin that stimulate the secretion.
Fi
F
Fig 6.1 Endogenous acid secretagogues.
Antagonists of acetylcholine, histamine and gastrin inhibit acid secretion.
Antisecretory drugs include: - H2-receptors blocking agents such as cimetidine, ranitidine, famotidine, nizatidine.
Cimetidine is the proto type of the group.
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Cimetidine dosage: PO 400mg 2 times/day, with meals and at bed time, or 800mg once daily
at bed time for 6-8 weeks.
Prophylaxis of recurrent ulcer, PO 400mg at bed time. High doses are used in the treatment of
Zollinger-Ellison syndrome.
Common adverse effects: muscular pain, headache, dizziness,
anti- androgenic effects at high doses such as impotence,gynecomastia,menstrual irregularities.
Drug interactions may occur when it is co-adminstered with warfarin, theophylline, phenytoin,
etc. and and the effects of the latter drugs is enhanced because of inhibition of the metabolism
of them.
Proton pump inhibitors such as, omeprazole, lansoprazole, etc. inhibit H+ -K+
-ATPase(proton
pump) which is the common terminal step in aa the three secretagogues to release hydrogen
ion into the gastric lumen.
Omeprazole dosage: – gastritis, gastroesophageal reflux disease, PO 20mg/day for 4-8 weeks;
zollinger-Ellison syndrome, PO 60mg once daily initially -120mg/day.
Peptic ulcer disease, PO 10-60mg/day. Adverse effects include headache, diarrhea and
nausea.
Anticholinergic agents such as pirenzepine, dicyclomine
Major clinical indication is prevention & treatment of peptic ulcer disease, Zollinger Ellison
syndrome, reflux esophagitis.
Anticholinegic drugs are not used alone in the treatment of peptic ulcer. However, they are
combined with H2-antagonists to further decrease acid secretion, with antacids to delay
gastric empting and thereby prolong acid – neutralizing effects, or with any anti-ulcer drug for
antispasmodic effect in abdominal pain.
C. Cytoprotective (mucosal protective) agents.
Locally active agents help to heal gastric and duodenal ulcers by forming a protective barrier
between the ulcers and gastric acid, pepsin, and bile salts. - They do not alter the secretion of gastric acid. These drugs include sucralfate and colloid
bismuth compounds. (e.g. tripotassium, dicitratobismuthate)- Colloidal bismuth compounds additionally exert bactericidal action against H.pylori
Other drugs that can to eradicate H.pylori such as amoxicillin, metronidazole, clarithromycin
and tetracycline are included in the anti-ulcer treatment regimens. - Protaglandins have both antisecretory and mucosal protective effects.
Example: Misoprostol– used for prevention of NSAID – induced ulcer.
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