Introduction to gastric juice Types of antacids 3 common types of antacids Usage and treatment Reaction & Mode of action Side effects Limitations Combination Drugs Conclusion
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
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)
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
Active ingredient: Basic metal salt Cations used are highlighted in Red Anions used: OH -, O 2-, CO 3 2-, HCO 3 -, HPO 3 -, Trisilicate (Mg), amino acetate (Al)
Commonly used: Al(OH) 3, MgOH, CaCO 3 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
Calcium CarbonateMagnesium 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 Most potent antacid ingredient; acts rapidly with more prolonged action than sodium bicarbonate Less potent that Ca Slow acting Can use hydroxide, phosphate & trisilicate (common in Singapore) Mild and slow acting antacid, last longer Most stable form of aluminium salts under normal conditions
Calcium CarbonateMagnesium Salts Aluminium Salts (usually hydroxide) Fast acting and long lasting effect Good when patient suffers from calcium deficiency hydroxide has the highest potency Magnesium antacids are generally NOT absorbed. Any small amounts are cleared renally May be dehydrated to form powder that readily dissolves in acids Insoluble in water and forms a suspension/gel that coats and protects the stomach lining Most appropriate if patient suffers from renal failure
Antacids can treats: Esophageal reflux / Heartburn – liquid preferred Gastric & Peptic Ulcer – relief pain while body heals Renal Stones – Al used to remove phosphate stone Constipation – Mg antacids given Patients suffering from Kidney failure/ uremic patient – only Al antacids allowed Calcium not given in Singapore Infants & Elderly not advised to take antacids
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 > Mg(OH) 2 > Al(OH) 3
CaCO 3 + 2 HCl CaCl 2 + H 2 O + CO 2 1g will neutralize 20mEq of acid CaCl 2 + CO 3 2- CaCO 3 + 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 Calcium is then removed through the renal system
Magnesium oxides, hydroxides and carbonates are poorly soluble, only Chloride are soluble. Mg(OH) 2 + 2HCl MgCl 2 + 2H 2 O 1 g can neutralize 2.7 mEq of acid MgCl + HCO 3 - MgCO 3 + HCl Although non-absorbable, 5% - 10% of Mg enter systemic circulation which then rapidly removed by kidney
Al(OH) 3 + 3HCl AlCl 3 + 3H 2 O Al(H 2 O) 6 3+ 1 g can neutralize 0.4 – 1.8 mEq of acid Solubility of Al increases as pH decrease, above ph>5 neutralizing effect will stop Al 3+ + PO 4 3- AlPO 4 (insoluble) Inadequate amount of phosphate ions will cause Al 3+ to be absorbed It will rebind back at soft tissue or bones where phosphates are found
Causes constipation Relaxation of the gastrointestinal smooth muscle delay in stomach emptying constipation Form insoluble complex of aluminum phosphate (AlPO 4 ), which is excreted in the faeces. 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
Causes diarrhea: 1. Mg 2+ 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 faeces, stimulating nerves in the intestines. 3. Mg 2+ also play a role in releasing the peptide hormone cholecystokinin, causing accumulation of water and electrolytes in the intestine and triggering intestinal motility.
Magnesium salts may cause central nervous depression in the presence of renal insufficiency Causes hypermagnesia 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
Release of CO 2 cause belching, nausea, abdominal distention, and flatulence. Calcium may induce rebound acid secretion. Calcium stone (kidney stone) can be formed. Excess Ca 2+ cause hypercalcemia. Not a problem in normal patients. But 3 - 4 g of CaCO 3 per day can be problematic in patients with uremia.
Antacids may affect drugs by altering gastric and urinary pH, (e.g., thyroid hormones) Al 3+ and Mg 2+ 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
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 Convenient to administer since it can carried around easily But it needs to be chewed properly
Simethicone Anti-flatulence drug to ease discomfort Breaking down gas bubbles in stomach by lowering the surface tension Alginates React with saliva to form a viscous raft of non-irritating material that floats atop stomach contents. When reflux occurs, refluxate consists of nonirritant materials Cannot be used with simethicone!
H 2 -Histimine Blockers Inhibit gastric acid secretion Proton Pump Inhibitors – Omeprezole Best for short-term and long term treatment of GERD But take long to take effect (approx 1-4 days)
WEBSITES Alu-cap, from Net Doctor. Website: http://www.netdoctor.co.uk/medicines/100000085.html http://www.netdoctor.co.uk/medicines/100000085.html Antacid Medication in Pregnancy May Increase Childhood Asthma, from Physorg.com. Website: http://www.physorg.com/news150121295.htmlhttp://www.physorg.com/news150121295.html Antacids, from MedTV. Website: http://gerd.emedtv.com/antacids/antacids.htmlhttp://gerd.emedtv.com/antacids/antacids.html Antacids: Facts and Discussion Forum and Encyclopaedia Articles, from Absolute Astronomy. Website: http://www.absoluteastronomy.com/topics/Antacidhttp://www.absoluteastronomy.com/topics/Antacid Antacids for GERD, from Quest Diagnostics. Website: http://www.questdiagnostics.com/kbase/topic/detail/drug/hw94857/detail.htm http://www.questdiagnostics.com/kbase/topic/detail/drug/hw94857/detail.htm Antacids, Information about Antacids, from Free Health Encyclopaedia. Website: http://www.faqs.org/health/topics/50/Antacids.html http://www.faqs.org/health/topics/50/Antacids.html Antacids: Over-the-counter (OTC) drugs, from Merck Website: http://www.merck.com/mmhe/sec02/ch018/ch018g.html http://www.merck.com/mmhe/sec02/ch018/ch018g.html Antacid | World of Chemistry Summary, from Book Rags. Website: http://www.bookrags.com/research/antacid-woc/ http://www.bookrags.com/research/antacid-woc/ Chemistry 104: Analysis of Antacid Tablet, from Chemistry LA Tech Website: http://www.chem.latech.edu/~deddy/chem104/104Antacid.htm http://www.chem.latech.edu/~deddy/chem104/104Antacid.htm
WEBSITES Information about Antacids, from RXList The Internet Drug Index. Website: http://www.rxlist.com/script/main/art.asp?articlekey=95545 http://www.rxlist.com/script/main/art.asp?articlekey=95545 Magnesium Trisilicate Tablets BP, from Net Doctor. Website: http://www.netdoctor.co.uk/medicines/100001573.html http://www.netdoctor.co.uk/medicines/100001573.html Minerals ~ Magnesium, from SpringBoard. Website: http://www.springboard4health.com/notebook/min_magnesium.html http://www.springboard4health.com/notebook/min_magnesium.html PharmGKB: Antacids, from Pharmokogenomics Knowledge Base. Website: http://www.pharmgkb.org/do/serve?objId=PA452298&objCls=Drug#tabview=tab1 http://www.pharmgkb.org/do/serve?objId=PA452298&objCls=Drug#tabview=tab1 What is Milk of Magnesia?, from Wise Geek. Website: http://www.wisegeek.com/what-is-milk-of-magnesia.htm http://www.wisegeek.com/what-is-milk-of-magnesia.htm
BOOKS Haddad L.M., Shannon M.W., Winchester J.F. (1998). Clinical Management of Poisoning and Drug Overdose Halter, F. (1981). Antacids in the Eighties: Symposium on Antacids, Hamburg. Munchen: Urban and Swarzenburg Kosegarten D.C., Pisano D.J. Vogenburg F.R. (2000). Mastering Pharmacy, licensure and certification: A case-based review. New York: McGraw-Hill Washington Neena. (1992). Antacids and Anti-reflux Agents. CRC Press Stoelting R.K. (2006) Handbook of Pharmacology and Physiology in Anaesthetic Practice. Philadelphia: Lippincott Williams and Wilkins Van Ness M.M., Gurney M.S., Jones D.M. (1995). Handbook of Gastrointestinal Drug Therapy. Boston: Little, Brown