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H/K
ECL cell P
histamine- transduction- HCl
secreting cell activation events
secretion
H/K
P
gastrin
receptor
paracrine
release of
Gastrin histamine
hormonal input ECL cell =
endocrine enterochromaffin-like cell
G cell =
gastrin-secreting cell
G cell
HOW IT WORKS AT THE RECEPTOR LEVEL
H/K
ECL cell P
histamine- transduction- HCl
secreting cell activation events
secretion
H/K
P
gastrin
receptor
paracrine
release of
Gastrin H-2 receptor blockers
histamine
hormonal input Tagamet
ECL cell =
endocrine Zantac
enterochromaffin-like
Pepcid cell
H/K ATPase pump
G cell = inhibitors
gastrin-secreting
Prilosec cell
G cell Nexium
Aciphex
NSAIDS
Protective Factors
Mucus Layer
• Physical Barrier ~ 0.5 mm thick on the surface of
the stomach and proximal duodenum.
• Consists of a mucus gel into which HCO3- is
secreted.
• Here, HCO3- neutralizes the acid diffusing into the
lumen pH gradient, even when the stomach
contents are at pH 2.
• PGs E2 and I2 synthesized by the gastric mucosa
cytoprotective action by stim the secretion of
mucus and HCO3- and by incr mucus blood flow.
Ulcer-Healing Drugs
Acid Secretion Reducers
• Histamine H2-receptor antagonists:
• Cimetidine and rantidine – orally rapidly
absorbed.
• Block the action of hist on parietal cells and decr
acid secretion.
• Relieve the pain of PU and incr rate of healing.
• Cimetidine binds cyt P-450 and may decr the
hepatic metabolism of other drugs (e.g., warfarin,
phenytoin, theophylline).
Ulcer-Healing Drugs
Acid Secretion Reducers
H+-Pump Inhibitors:
• Omeprazole and lansoprazole – inactive at
neutral pH.
• But in acid, they rearrange into 2 types of reactive
molecule react with sulphydral groups in the
H+/K+-ATPase (H+ pump) responsible for
transporting H+ ions out of parietal cells.
• This enzyme is irreversibly inhibited: So, when
would acid secretion resume?
• Particularly useful in patients with severe
gastric acid hypersecretion caused by
Zollinger-Ellison syndrome and Cushing’s
ulcers:
• Zollinger-Ellison Syndrome: gastrin-secreting
tumour of the non-β cells (pancreas) incr
acid secretion.
• Cushing’s Ulcers: in patients with severe head
injuries, increased vagal (Ach) tone gastric
hyperacidity.
Ulcer-Healing Drugs
Mucosal Strengtheners
Sucralfate polymerizes below pH 4 a very sticky gel
that adheres strongly to the base of ulcer craters.
Bismuth chelate (tripotassium dicitratobismuthate) acts
similarly to sucralfate.
Strong affinity for mucosal glycoproteins, esp in the
necrotic tissue of the ulcer craters, which become
coated in a protective layer of polymer-glycoprotein
complex.
Bismuth may blacken the teeth and stools.
Bismuth and sucralfate must be given on an empty
stomach or they will complex with food proteins.
Antacids
• The incr in rate of incr the luminal pH incr the
rate of gastric emptying effect is short.
• Gastrin release is incr and, because this
acid release, larger amts of antacids are
needed than would be predicted (acid
rebound).
• Frequent high doses of antacids promote ulcer
bleeding, but not practical.
Antacids (cont’d)
• NaHCO3-: the only useful H2O-soluble antacid.
Acts rapidly, but has a transient action. High
doses may systemic alkalosis.
• Mg(OH)2 and Mg trisilicate are H2O-insoluble and
have a fairly rapid action. Mg has a laxative effect
and may diarrhea.
• Al(OH)3: relatively slower action. Al3+ ions form
complexes with certain drugs (e.g., tetracyclines)
and tend to cause constipation.
• Mixtures of Mg and Al may be used to minimize
the effects on motility.
Motility and Secretions: Motility Stimulants