Clinical pharmacology

1. Acid secretion and antacids
Domina Petric, MD

2. PHYSIOLOGY OF ACID
SECRETION
I.

3. The parietal cell contains
receptors for gastrin
(CCK-B), histamine (H2)
and acetylcholine
(muscarinic, M3).
Acid secretion

4. Acid secretion
When acetylcholine (from vagal
postganglionic nerves) or gastrin (released
from antral G cells into the blood) bind to the
parietal cell receptors, they cause an increase
in cytosolic calcium.
Cytosolic calcium in turn stimulates protein
kinases that stimulate acid secretion from
H+/K+-ATPase (the proton pump) on the
canalicular surface.

5. Acid secretion
Gut endocrine cells are called
enterochromaffin-like (ECL) cells.
ECL cells have receptors for gastrin
and acetylcholine which stimulate
histamine release.

6. Acid secretion
Histamine binds to the H2
receptor on the parietal cell.
Activation of adenylyl cyclase.
Increase of intracellular cyclic
adenosine monophosphate (cAMP).
Activation of protein kinases that stimulate
acid secretion by the H+/K+-ATPase.

7. Acid secretion
• The major effect of gastrin upon
acid secretion is mediated
indirectly through the release of
histamine from ECL cells rather
than through direct parietal cell
stimulation.
• Acetylcholine provides potent
direct parietal cell stimulation.

8. ANTACIDS
II.

9. Antacids

10. Antacids
Antacids are weak bases
that react with gastric
hydrochloric acid to form
a salt and water.
Principal mechanism of
action is reduction of
intragastric acidity.

11. Antacids
• After a meal, 45 mEq/h of
hydrochloric acid is secreted.
• A single dose of 156 mEq of
antacid given 1 hour after a
meal effectively neutralizes
gastric acid for up to 2 hours.

12. Sodium bicarbonate
• It reacts rapidly with
hydrochloric acid (HCL) to
produce carbon dioxide and
sodium chloride.
• Formation of carbon dioxide
results in gastric distention
and belching.

13. Sodium bicarbonate
Unreacted alkali is readily
absorbed.
Given in high doses or to patients
with renal insufficiency, sodium
bicarbonate can cause metabolic
alkalosis.
Sodium chloride absorption may
exacerbate fluid retention in patients
with heart failure, hypertension and
renal insufficiency.

14. Calcium carbonate
• Calcium carbonate is less soluble
and reacts more slowly than
sodium bicarbonate with HCL to
form carbon dioxide and calcium
chloride (CaCl2).
• It may cause belching and
metabolic alkalosis.

15. Warning!
Excessive doses of both sodium
bicarbonate or calcium carbonate with
calcium-containing dairy products can
lead to MILK-ALKALI SYNDROME:
• hypercalcemia
• renal insufficiency
• metabolic alkalosis

16. Magnesium/aluminium hydroxide
• Formulations with magnesium or
aluminium hydroxide react slowly
with HCL to form magnesium
chloride or aluminium chloride and
WATER.
• There is no belching.
• Metabolic alkalosis is also
uncommon.

17. Magnesium/aluminium hydroxide
• Unabsorbed magnesium salts
may cause an osmotic diarrhea.
• Unabsorbed aluminium salts may
cause constipation.
• These agents are commonly
administered together in
proprietary formulations.

18. Magnesium/aluminium hydroxide
• Both magnesium and
aluminium are absorbed and
excreted by the kidneys.
• Patients with renal
insufficiency should not take
these agents long-term.

19. Interactions
All antacids may affect the absorption
of other medicinations by:
• binding the drug and reducing its
absorption
• increasing intragastric pH so that the
drug´s dissolution or solubility is
altered (especially weakly basic or
acidic drugs)

20. Interactions
Antacids should not be
given within 2 hours of
doses of tetracyclines,
fluoroquinolones,
itraconazole and iron.

21. Literature
• Katzung, Masters, Trevor.
Basic and clinical
pharmacology.