Chemistry of antacids

1. Chemistry of antacids ChiaJia Yan U062203H Lee Dang Ni U051984H Lim Chai Ying U062410N Lim RenHann U062774H

2. Content • Introduction • Types of antacids • Usage and treatment • Mode of action & reaction • Side effects • Combination Drugs • Conclusion

3. Introduction • Stomach contains gastric acid of pH of 2 to 3. • Gastric acid contains HCl, KCl and NaCl. • Excess acid can cause pH to fall below 2 which can cause problems such as abdominal pain and heartburn etc. • Gastric juice activates pepsin, an enzyme that carries out proteolysis – break down proteins by breaking bonds that links amino acids

4. Gastric Juice Parietal cell produce gastric acid using proton pump H+/K+ATPase, an enzyme. As a proton pump, it transport 1 H+ in exchange of 1 K+ from stomach against concentration gradient with ATP providing the energy. Epithelial cells • Picturetaken from My Optum Health. http://www.myoptumhealth.com/portal/DiseasesandConditions/item/Gastroesophageal+reflux+disease+and+hea?section=2 (accessed on 8 April 2009)

5. Antacids • Alkaline salt or buffer substances used to neutralize stomach acid and bring its pH back to 2 to 3 • Treat indigestion or relieve any discomfort caused by acidity of stomach acid • Reduces acid concentration within the lumen of the esophagus which increase the intra-esophageal pH and decrease pepsin activity • In forms of tablet, liquid suspension ,lonzenges, chewing gum, dissolving tablet • Liquid relief symptoms faster

6. Types of Antacids • Active ingredient: Basic metal salt Cations used are highlighted in Red • Anions used: OH-, O2-, CO32-, HCO3-, HPO3-, Trisilicate (Mg), amino acetate (Al)

7. Types of Antacids • Commonly used: Al(OH)3, MgOH, CaCO3 By mixing and matching cations and anions, combining different types of antacids, unique attributes, properties and potency of antacids are created. Either Mixture or Complex antacids Other common ingredient: • Simethicone – relieve gas by breaking down bubbles • Alginic acid – foaming agent that floats on top of stomach content

8. 3 Common Antacids

9. 3 Common Antacids

10. Usage and Treatments • Antacids needs to be in hydrated form for better neutralizing effect Aluminium Antacids • Aluminium based antacids preferred for kidney failure patient as it can be used to remove excess phosphate ions • Other usage: Magnesium used as a laxative for constipated patient

11. Reactions • Strength of an antacid to neutralize acid in the stomach is determined using the antacid’s neutralizing capacity (ANC) • ANC is expressed as milliequivalents (mEq) of the amount of 1N HCl that can be neutralized • FDA: all antacids must have a neutralizing capacity of at least 5 mEq per dose. • The commonly used antacids are ranked in this order with respect to ANC, from strongest to weakest • CaCO3 > NaHCO3 > Mg(OH)2 > Al(OH)3

12. Reactions - Ca • CaCO3 + 2 HCl  CaCl2 + H2O + CO2 1g will neutralize 20mEq of acid • CaCl2 + CO32- CaCO3 + Cl- (higher pH in intestine) • Some unchange calcium is absorbed by the gut, which can raise the pH of the blood causing alkalosis –can affect proteins

13. Reactions - Mg • Magnesium oxides, hydroxides and carbonates are poorly soluble, only Chloride are soluble. • Mg(OH)2 + 2HCl  MgCl2 + 2H2O 1 g can neutralize 2.7 mEq of acid • MgCl + HCO3- MgCO3 + • Although non-absorbable, 5% - 10% of Mg enter systemic circulation which then rapidly removed by kidney

14. Reactions - Al • Al(OH)3 + 3HCl  AlCl3 + 3H2O Al(H2O)63+ 1 g can neutralize 0.4 – 1.8 mEq of acid • Solubility of Al increases as pH decrease

15. Reaction- complex antacids • Complex antacids can be used. E.g. Magaldrate [Mg(OH)Al2(OH)10]4-.2H2O

16. Side Effect – Al(OH)3 • Causes constipation • Relaxation of the gastrointestinal smooth muscle delay in stomach emptying constipation • Form insoluble complex of aluminum phosphate (AlPO4), which is excreted in the feces. May lead to lowered serum phosphate concentrations and phosphorus mobilization from the bone. If phosphate depletion is already present, osteomalacia, osteoporosis, and fracture may result BUT it reduce phosphates in the urine and prevent formation of phosphatic (struvite) urinary stones

17. Side Effect – Mg Salt • Causes diarrhea: 1. Mg2+ draw water from the surrounding body tissues into the intestinal tract by osmosis.2. Higher quantity of water in the intestinal tract softens and increases the volume of feces, stimulating nerves in the intestines.3. Mg2+ also play a role in releasing the peptide hormone cholecystokinin, causing accumulation of water and electrolytes in the intestine and triggering intestinal motility.

18. Side Effect – Mg Salt • Magnesium salts may cause central nervous depression in the presence of renal insufficiency • Causes hypermagnesaemia in patients with severe renal function impairment BUT Magnesium hydroxide inhibits the precipitation of calcium oxalate and calcium phosphate, thus preventing the formation of calcium stones

19. Side Effect – CaCO3 • Release of CO2 cause belching, nausea, abdominal distention, and flatulence. • Calcium may induce rebound acid secretion. • Calcium stone (kidney stone) can be formed. • Excess Ca2+ cause hypercalcemia. Not a problem in normal patients. But 3 - 4 g of CaCO3 per day can be problematic in patients with uremia.

20. Antacids-Drugs Interaction • Antacids may affect drugs by altering gastric and urinary pH, (e.g., thyroid hormones) • Al3+ and Mg2+ antacids are notable for their propensity to chelate other drugs present in the GI tract, forming insoluble complexes that pass through the GI tract without absorption • Most interactions can be avoided by taking antacids 2 hours before or after ingestion of other drugs

21. Limitation • Require large neutralizing capacity single dose (156 meq) antacid 1 hr after meal  neutralize gastric acid for 2 hr 2nd dose 3 hr after eating  maintains effect for > 4 hr • Tablet antacids generally weaker  large number required • Very inconvenient to adminster

22. Reference • Pictures: • http://www.specialtyminerals.com/specialty-applications/specialty-markets-for-minerals/pharmaceuticals/antacids/ • NiDDK Image Library, http://www.catalog.niddk.nih.gov/imagelibrary/detail.cfm?id=124