Antacids

For BDS 2nd Year

1. Antacids Dr. Pravin Prasad MBBS, MD Clinical Pharmacology Assistant Professor, Department of Clinical Pharmacology Maharajgunj Medical Campus, TU 10 March 2020 (27 Falgun 2076), Tuesday

2. By the end of this discussion, BDS 1 st year students will be able to: Discuss the rationale of having gastric acid in the stomach Enlist the problems due to increased gastric acid secretion Classify the drugs used as antacids Understand the differences among drugs used as antacids Explain the basis of combination of antacids

3. Normal Physiology Stomach contents are highly acidic Due to secretion of hydrochloric acid from parietal cells of gastric epithelium pH as low as 1-2 Required for: Killing bacteria that comes in with food Optimal activity of digestive enzymes

4. Factors increasing gastric acid secretion Alcohol consumption Eating certain foods Spicy food Oily food Emotional stress: Anxiety Stress Smoking Certain Drugs, i.e. Aspirin

5. Consequences of Increased acid in stomach Subjective Discomfort Pain Indigestion Sour brash (Reflux) Esophageous Inflammation Cancer Stomach Ulcer Bleeding

6. Introduction Basic substances which neutralize gastric acid and raise pH of gastric contents Includes: Aluminum Hydroxide, Magnesium Carbonate, And Magnesium Trisilicate Are Available As Tablets And Liquids May be combined with: Simethicone: reduces flatulence Alginates: protects the lining of the esophagus (gullet) from stomach acid Sodium Alginate And Alginic Acid

7. Antacids: Classification Systemic: Sodium bicarbonate Sodium citrate Non-systemic: Magnesium hydroxide Mag. Trisilicate Aluminium hydroxide gel Magaldrate Calcium carbonate

8. Antacids: Mechanism of Action Neutralises the gastric acid Acid Neutralising Capacity: number of mEq of 1N HCl that are brought to pH 3.5 in 15 min (or 60 min in some tests) by a unit dose of the antacid preparation Leads to: Decrease in pain Allow the ulcers to heal Decreases the activity of pepsin Secreted as an inactive form, gets activated in pH < 4 May lead to rebound acidity

9. Systemic antacids Sodium bicarbonate water soluble, acts instantaneously, but the duration of action is short Potent neutralizer (1 g → 12 mEq HCl), pH may rise above 7 Disadvantages: Absorbed systemically: large doses will induce alkalosis. Produces CO 2 in stomach → distention, discomfort, belching, risk of ulcer perforation Acid rebound occurs, but is usually short lasting Increases Na + load: may worsen edema and CHF Uses: Casual treatment of heartburn Alkalinize urine and to treat acidosis Sodium citrate 1 g neutralizes 10 mEq HCl CO 2 is not evolved

10. Non systemic antacids Insoluble and poorly absorbed basic compounds react in stomach to form the corresponding chloride salt Chloride salt again reacts with the intestinal bicarbonate so that HCO 3 ¯ is not spared for absorption—no acid-base disturbance occurs However, small amounts that are absorbed have the same alkalinizing effect as NaHCO 3

11. Non systemic antacids Mag. Hydroxide: low water solubility: its aqueous suspension (milk of magnesia) has low concentration of OH¯ ions and thus low alkalinity Reacts with HCl promptly and is an efficacious antacid (1 g → 30 mEq HCl) Rebound acidity is mild and brief

12. Non systemic antacids Magnesium trisilicate Low solubility and reactivity 1 g can react with 10 mEq acid, but in clinical use only about 1 mEq is neutralized About 5% of administered Mg is absorbed systemically—may cause problem if renal function is inadequate All Mg salts have a laxative action by generating osmotically active MgCl 2 in the stomach and through Mg 2+ ion induced cholecystokinin release

13. Non systemic antacids Aluminium hydroxide gel bland, weak and slowly reacting antacid Little acid neutralization obtained at conventional doses The Al 3+ ions relax smooth muscle: delays gastric emptying (constipation) Binds phosphate in the intestine and prevents its absorption—hypophosphatemia occurs on regular use leading to: osteomalacia Be used as therapeutically in hyperphosphatemia and phosphate stones. Small amount of Al 3+ that is absorbed is excreted by kidney Aluminium toxicity (encephalopathy, osteoporosis) in renal failure

14. Non systemic antacids Magaldrate hydrated complex of hydroxymagnesium aluminate that initially reacts rapidly with acid and releases alum. hydrox . which then reacts more slowly The freshly released alum. hydrox . is in the unpolymerized more reactive form Thus, magaldrate cannot be equated to a physical mixture of mag. and alum. Hydroxides It is a good antacid with prompt and sustained neutralizing action. Its ANC is estimated to be 28 mEq HCl/g

15. Non systemic antacids Calcium carbonate P otent and rapidly acting acid neutralizer (1 g → 20 mEq HCl) ANC of commercial preparations is less and variable due to differing particle size and crystal structure Though it liberates CO 2 in the stomach at a slower rate than NaHCO 3 , it can cause distention and discomfort Ca 2+ ions are partly absorbed Increase HCl production directly by parietal cells as well as by releasing gastrin Mild constipation or rarely loose motions Can be dangerous in renal insufficiency

16. Antacid combinations Fast (Mag. hydrox .) and slow (Alum. hydrox .) acting components yield prompt as well as sustained effect Mag. salts are laxative, while alum. salts are constipating: combination may annul each other’s action and bowel movement may be least affected Gastric emptying is least affected; while alum. salts tend to delay it, mag./cal. salts tend to hasten it Dose of individual components is reduced; systemic toxicity (dependent on fractional absorption) is minimized.

17. Conclusion Strong gastric acid is responsible for killing of micro-organisms present with the food and for activation of pepsin enzyme Increased gastric acid secretion may present as subjective discomfort to cancer of related organs Antacids can be both systemic and non-systemic Antacids differ and are compared in terms of acid neutralising capacity Problems of one antacid can be minimised by using another antacid

18. Questions?? Thank you..