1. Acid secretion and antacids
Domina Petric, MD

2. Physiology of acid secretion

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

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. Acetylcholine provides potent direct parietal cell stimulation.
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. II.
antacids

9. Antacids
Today antacids are used by patients as nonprescription remedies for the treatment of intermittent heartburn and dyspepsia.

10. Principal mechanism of action is reduction of intragastric acidity.
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. Unreacted alkali is readily absorbed.
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. It may cause belching and metabolic alkalosis.
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.