CHEMISTRY OF ANTACIDS

Chia Jia Yan U062203HLee Dang Ni U051984HLim Chai Ying U062410NLim Ren Hann U062774H

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

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

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

Picture taken from My Optum Health. http://www.myoptumhealth.com/portal/DiseasesandConditions/item/Gastroesophageal+reflux+disease+and+hea?section=2 (accessed on 8 April 2009)

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

Types of Antacids Active ingredient: Basic metal salt

Cations used are highlighted in Red Anions used: OH-, O2-, CO3

2-, HCO3-, HPO3

-, Trisilicate (Mg), amino acetate (Al)

Types of Antacids Commonly used: Al(OH)3, MgOH, CaCO3

By mixing and matching cations and anions, combiningdifferent types of antacids, unique attributes, properties

andpotency 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

Calcium Carbonate

Magnesium Salts

Aluminium Salts (usually

hydroxide) Most potent

antacid ingredient; acts rapidly with more prolonged action than sodium bicarbonate

Fast acting and long lasting effect

Good when patient suffers from calcium deficiency

Can use hydroxide, phosphate and trisilicate (common in Singapore)

Less potent that Ca hydroxide has the

highest potency Slow acting Magnesium

antacids are generally NOT absorbed. Any small amounts are cleared renally

Most stable form of aluminium salts under normal conditions

May be dehydrated to form powder that readily dissolves in acids

Mild and slow acting antacid, last longer

Insoluble in water and forms a suspension/gel that coats and protects the stomach lining

Most appropriate if patient suffers from renal failure

3 Common Antacids

Calcium Carbonate

Magnesium Salts

Aluminium Salts (usually

hydroxide) Alka-mints tablets Childrens’ Mylanta

Tablet Chooz Gum Alcalak Titralac

Milk of Magnesia

Philips Tablets Philips Oral

Suspension

Maalox Mylanta ALternaGEL

Brand Names & AOB

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

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

Reactions - Ca CaCO3 + 2 HCl CaCl2 + H2O + CO2

1g will neutralize 20mEq of acid CaCl2 + CO3

2- 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

Reactions - Mg Magnesium oxides, hydroxides and carbonates

are poorly soluble, only Chloride are soluble.

Mg(OH)2 + 2HCl MgCl2 + 2H2O1 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

Reactions - Al Al(OH)3 + 3HCl AlCl3 + 3H2O Al(H2O)6

3+

1 g can neutralize 0.4 – 1.8 mEq of acid

Solubility of Al increases as pH decrease

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

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

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.

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

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.

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

Antacids-Drugs Interaction

Require large neutralizing capacity single dose (156 meq) antacid 1 hr after meal neutralize gastric acid for 2 hr2nd dose 3 hr after eating maintains effect for > 4 hr

Tablet antacids generally weaker large number required

Very inconvenient to adminster

Limitation

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