1. D4 pH regulation of the stomach

2.  Understand that antacids can be used to reduce the amount of excess acid in the stomach.  Understand that the action of antacids is non- specific  Write equations for neutralisation reactions involving different antacids  Understand how ranitidine (Zantac®) works  Understand how omeprazole (Prilosec®) and esomeprazole (Nexium®) work  Understand what is meant by an active metabolite  Solve problems involving buff er solutions

3.  Normal pH of stomach is 1 to 2  Hydrochloric acid is produced in stomach by million if glands on the wall of the stomach.  Two reason for stomach to maintain low pH 1. The low pH plays a role in the body’s natural defense against disease-causing microorganisms 2. The digestive enzymes in the stomach (e.g. pepsin, which breaks down proteins) require a low pH for optimum catalytic activity.

5. Excess of acid in stomach can damage mucous layer that protect the stomach wall. This can result in the following: Indigestion, heartburn and peptic ulcer 1. indigestion – irritation of the stomach lining caused by excess acid producing pain or discomfort in the upper abdomen and/or nausea 2. heartburn (acid reflux) – acid from the stomach rising up into the esophagus causing a burning sensation 3. peptic ulcer – erosion of part of the gut lining, caused by acid penetrating the mucous layer. This is a serious condition if not treated can lead to internal bleeding.

6.  Excess stomach acid results in a state of discomfort known as acid indigestion  Acid indigestion may result form a variety of factors including:  Overeating  Alcohol consumption  Eating certain foods  Anxiety  Smoking  Certain Drugs, i.e. Aspirin 6

7.  Antacids are weak bases that are used to neutralize excess stomach acid  Most antacids are weak inorganic bases  Common examples include  CaCO 3  NaHCO 3  Al(OH) 3  Mg(OH) 2  MgO and Mg(OH) 2 (Milk of Magnesia) 7

8.  Antacids are non-specific and do not bind to protein receptors. They work by simply neutralising excess stomach acid.

9.  Antacids react with HCl in the stomach  Some common antacid reactions include: CaCO 3 + 2 HCl  CaCl 2 + H 2 O + CO 2 NaHCO 3 + HCl  NaCl + H 2 O + CO 2 Al(OH) 3 + 3 HCl  AlCl 3 + 3 H 2 O Mg(OH) 2 + 2 HCl  MgCl 2 + 2 H 2 O MgO + 2 HCl  MgCl 2 + H 2 O 9

10.  In addition to neutralizing excess stomach acid they may be helpful in preventing inflammation, relieving pain and discomfort, and allowing the mucus layer in the stomach lining to heal.  They are often used to treat ulcers by preventing the stomach acids from attacking the stomach lining allowing it to heal. Mucus Lining 10

11.  Antacids are relatively harmless but they can have minor contraindications  Magnesium Compounds may cause diarrhea  Aluminum Compounds may cause constipation and they also may interfere with the adsorption of phosphates in the formation of bones. This is more likely to be true if they are taken for an extended period of time  Carbonates may generate carbon dioxide leading to bloating and flatulence. 11

12.  Antacids are often combined with alginates and anti-foaming agents.  Aliginates float on the stomach contents to form a neutralizing layer preventing reflux of stomach acids up into the esophagus. Hence they help to prevent acid reflux or heart burn.  Anti-foaming agents such as simethicone (dimethicone) prevent the formation of gases and reduce flatulence. 12

13.  Compare the volume of stomach acid (hydrochloric acid) of pH 1.50 that is neutralised by taking one indigestion tablet containing 1.00 g of calcium carbonate with one containing 1.00 g of sodium hydrogencarbonate. Example

14.  A pH of 1.50 corresponds to a concentration of H + (aq) of 10 −1.50 = 0.0316 mol dm −3  Because HCl is a strong acid it completely dissociates and the concentration of H + (aq) is equal to the original concentration of the acid.

16. SO 1.00 g of calcium carbonate therefore reacts with significantly more hydrochloric acid

17. a 3.85 dm 3 ; b 3.43 dm 3

19.  Peptic ulcer  It is a sore in stomach ( gastric ulcer ) or in upper part of small intestine (Duodenal ulcer)  10 to 20 percent people suffer from peptic ulcer  Disease is very painful and can fetal

20.  Two main approaches to treat peptic ulcer 1. Stopping the production of acid 2. Preventing the release of acid into the stomach Note: Term H2 blocker or receptor will be used a lot. But it has nothing to do with H 2 gas

21.  H2 blockers impede acid production in the stomach by blocking the actions of histamine, a substance produced by the body that encourages acid secretion in the stomach.  These drugs cannot cure ulcers, but in certain cases they are useful. They are effective only for duodenal ulcers, however, and have little effect on stomach (gastric) ulcers. 21

22.  Ranitidine or Zantac® is a drug that inhibits the production of acid.

23.  It binds with receptor protein (histamine H 2 -receptor) in cell membrane and stops normal chemical messenger (histamine) from binding with cell membrane.  Ranitidine stops production stomach acid.  Ranitidine can be described as an H 2 -receptor antagonist because when it binds to an H 2 - receptor it does not cause activation of the receptor, but rather stops the naturally occurring molecule that does cause activation (the agonist) from binding.

24.  Proton Pump Inhibitors reduce the production of acid by blocking the enzyme in the wall of the stomach that produces acid.  Inhibitors do not neutralize excess acid but inhibit the initial production of hydrochloric acid  The reduction of acid prevents ulcers and allows any ulcers that exist in the esophagus, stomach and duodenum to heal. 24

25.  Omeprazole (Losec®, Prilosec®) and esomeprazole (Nexium®) are proton pump inhibitors and work by preventing the release of acid from the parietal cells into the stomach. Esomeprazole is a stereoisomer of this

26.  Protons are released from the parietal cell by the action of a proton pump. This is a protein complex that moves protons through cell membranes – being charged, protons cannot diffuse normally through a cell membrane made of mainly non-polar lipid molecules.  These drugs are weak bases but are mainly in the un-ionised form at the pH of blood plasma.  They are also mostly non-polar and therefore lipid-soluble so they can pass through the cell membrane of the parietal cells.

27.  Inside the parietal cells the medium is much more acidic and the basic molecules get protonated. Protonation starts a series of reactions that changes the structure of the drug molecule into one that can bind irreversibly to the proton pump and so stop it from carrying out its function. The drugs are effective for an extended period of time – until the cell is able to make new proton pumps.

28.  Active metabolites are the active forms of drugs after they have been processed in the body.  codeine is converted into morphine in the body and it is the morphine that binds much more strongly to the opioid receptors than codeine, producing an analgesic effect  omeprazole/esomeprazole are converted into different forms that are able to bind to proton pumps  aspirin is converted into the active form – salicylic acid.

29.  To avoid side effects – e.g. aspirin  To allow the drug to pass through cell membranes. e.g Diamorphine  To allow the drug to dissolve in water more easily – e.g. fosphenytoin  To target drugs to a particular area e.g omeprazole

30.  A buffer solution is one that resists changes in pH when small amounts of acid or alkali are added. The graph in Figure shows the result of adding 10 cm 3 of 0.100 mol dm −3 hydrochloric acid in stages to 100 cm 3 of water (blue line) and to 100 cm 3 of a buffer solution (orange line).

31.  A buffer solution consists of two components – a acid and a base.  A weak acid and its conjugate base or A weak base and its conjugate acid.  The base reacts with any acid added and the acid reacts with any base added. There must be reasonably large amounts of each present for the solution to function as a buffer.

32.  Consider a general buffer containing acid, HA and base A −. The equilibrium that exists in this solution is:  When acid is added  When a base is added

33.  Henderson–Hasselbalch equation:

36.  A buffer pH range can be calculated as  pH= pKa -1 to pH = pKa +1  E.g a buffer dihydrogen Phosphate (pka 2.12) works effectively between 1.12 to 3.12.  Outside this range buffer loses its ability to maintain constant pH.