The middle and upper parts of the stomach act as a reservoir for food; the part near its outlet into the duodenum contracts and relaxes to churn and mix the food. The rate of emptying of the stomach varies with the volume of contents: the greater the volume the faster the rate of emptying. A fatty meal delays emptying; so does an increase in stomach acidity. Some drugs increase and some decrease the rate of emptying of the stomach. Another important function of the stomach is to make digestive juice. This contains hydrochloric acid (about one and a half litres are produced every day), mucus which protects the surface of the stomach and an enzyme called pepsin which helps to digest protein in food.

The stomach can get ‘upset’ if its lining is irritated (e.g. by aspirin or alcohol), by eating too much, by eating unusual food, or by virus or bacterial infections. The lining of the stomach can also become ‘inflamed’ (gastritis). This may be caused or aggravated by many things; for example, certain foods (pickles, fried food), alcohol and smoking. This irritation or inflammation may produce symptoms such as discomfort, nausea, pain and loss of appetite. These symptoms are usually referred to as indigestion or dyspepsia. Sometimes the surface of the stomach may become eroded to produce a peptic ulcer. A peptic ulcer may occur in the oesophagus (gullet), stomach (where it may be called a gastric ulcer) and in the duodenum (duodenal ulcer).

Relatively little is known about the factors which cause peptic ulcers, but there is evidence that acid and pepsin are partly responsible. However, ‘normal’ stomachs do not develop ulcers. Therefore, the ‘normal’ lining of the stomach must be protective, and it may be something affecting this protection that causes ulcers. This may be related to the mucus that covers the surface, the ability of the mucous cells to renew themselves every few days, the nutrition of the stomach itself, its blood supply, and various chemical factors. There are other factors such as heredity (there is often a family history), seasonal factors, diet, smoking, alcohol, and particularly, worry and stress.

The symptoms of peptic ulcer usually start with ‘indigestion’ but may start with acute pain, or bleeding or perforation. Indigestion going on for more than several days may be due to a peptic ulcer, particularly if the episodes keep recurring and if accompanied by pain rather than ‘discomfort’. Pain from a duodenal ulcer often comes on when you are hungry and it wakes you in the night; whereas a gastric ulcer pain may come on fairly soon after food. Food, antacids or vomiting may relieve peptic ulcer pains.

You should consult your doctor if you have indigestion lasting more than a few weeks or recurring at intervals – you may have a peptic ulcer. The treatment of a peptic ulcer includes advice on diet – which means taking a well-balanced diet and frequent, regular, small meals. You should avoid alcohol and any foods which you know give you pain. You should stop taking coffee and avoid any drugs known to irritate the stomach; for example, aspirin, and most drugs used to treat rheumatism and arthritis. You should also stop smoking. There is no point in filling yourself full of indigestion mixture while continuing to smoke and drink alcohol. If you are worried, anxious or tense then you need help and advice on sorting out the stresses which are affecting you.

The main drugs used to treat peptic ulcers fall into three groups – drugs which neutralize the acid in the stomach (antacids), drugs which reduce the production of acid by the stomach cells and drugs which help to protect the stomach lining.

Note: Eradication of H. pylori infection should be considered in all patients with peptic ulcers (see later).

1. Drugs which Neutralize the Acid in the Stomach

Antacids neutralize the acid in the stomach contents and this relieves indigestion and the pain of a peptic ulcer. They consist of mixtures of various base salts of sodium, magnesium, calcium, aluminium and bismuth. The amount needed to neutralize stomach acid depends upon the rate of acid production by the stomach, the presence or absence of food, and upon the rate of emptying of the stomach. Antacids may be absorbed into the blood-stream and produce changes in the chemistry of the blood. This effect is often of no consequence, because the kidneys quickly restore the chemical balance. However, in patients with impaired kidney function this may be dangerous.

Sodium bicarbonate relieves pain rapidly, but its effects quickly wear off and it may cause changes in the blood chemistry. It releases carbon dioxide gas into the stomach which causes belching (this makes some people think it is working effectively) but it may also cause distension of the stomach, which is unpleasant. It is useful for quick relief but there is nothing to recommend its continued use. Patients with impaired heart or kidney functions should not use it because of the high sodium content. Also, it should not be used by patients with fluid retention (oedema) or raised blood pressure because it increases the blood salt level and may cause further retention of water by the kidneys.

Magnesium salts act slowly. They may cause diarrhoea and some magnesium may be absorbed into the blood-stream – they should not be used in patients with impaired kidney function.

Calcium carbonate acts quickly and effectively. Some calcium is absorbed into the blood-stream. If patients with peptic ulcers take a milk diet (which is high in calcium) and calcium carbonate regularly for long periods of time they may develop a high level of blood calcium, which may cause a group of symptoms – loss of appetite, nausea, vomiting, headache, weakness, abdominal pains, constipation and thirst. This is often called the milk-alkali syndrome (‘syndrome’ being the term used to indicate a group of signs and symptoms). Temporary or permanent kidney damage may occur. Calcium salts tend to constipate; they are, therefore, often given mixed with magnesium salts.

Aluminium hydroxide is slow to act. It does not alter the blood chemistry because it forms insoluble complexes in the stomach. Aluminium hydroxide and other aluminium compounds constipate.

Bismuth salts are not very effective as antacids and may produce toxic effects when absorbed, particularly in patients with impaired kidney function.

The Use of Antacids

Antacids relieve the symptoms of indigestion whether due to an ulcer or not (non-ulcer dyspepsia). They are also useful in relieving the pain caused by inflammation of the gullet (oesophagitis). None of the available antacids is ideal. They vary in their rate and duration of action and in the amounts required to neutralize the acid contents of the stomach. Liquid preparations and powders mixed with water are more effective than tablets. Tablets should be sucked slowly between meals; their routine use after meals to prevent symptoms is of no use. Because no specific antacid can be recommended, mixtures are generally used. Mixtures also help to avoid bowel complications such as diarrhoea from magnesium salts and constipation from calcium or aluminium salts.

Antacids interfere with the absorption of many drugs eg. iron, vitamin supplements, aspirin, tetracycline antibiotics and cimetidine. Some have a high sodium content (salt) and should not be used by patients having treatment for raised blood pressure, heart failure, liver failure or in pregnancy – always check with your pharmacist or doctor.

Combined Formulations

Some antacid mixtures contain drugs which disperse wind (e.g. activated dimeticone) and drugs which spread the antacid over the surface of the stomach contents to form an alkaline raft which provides a “mechanical” barrier to protect the lower end of the oesophagus from acid reflux. These latter include co-dried gels and complexes of silicates and alginic acid. They are useful in the treatment of heartburn.

For repeated use, soluble antacids such as sodium bicarbonate should be avoided. Comparable antacid preparations are not necessarily equivalent in their ability to neutralize the acid. Do not forget that the speed of action of antacids depends upon their ability to neutralize the acid in the stomach. This depends principally upon the speed with which they dissolve and the rate of emptying of the stomach. The choice is really what suits you and the right dose is what relieves your symptoms. The most expensive are not necessarily the best.

2. Drugs which Reduce Acid Production by the Stomach

H₂-receptor Blockers

H₂ antihistamine drugs block the histamine receptors in the stomach (see Chapter 17). This results in a reduction in both the volume and acidity of the gastric juice, which encourages healing of peptic ulcers and reduces the risk of reflux.

The H₂ antihistamines, for example cimetidine (Acitak, Dyspamet, Galenamet, Peptimax, Phimetin, Tagamet, Ultec, Zita), famotidine (Pepcid), nizatidine (Axid, Zinga) and ranitidine (in Pylorid, Rantec, Ranitic, Zaedoc, Zantac), heal peptic ulcers, particularly duodenal ulcers. They are also of use in oesophagitis, acid reflux and non-ulcer dyspepsia.

Initial treatment of peptic ulcer should preferably last for 4–6 weeks. A daily maintenance of half the treatment dose will prevent relapse but do not forget that they do not cure; after stopping them, ulcers may recur. Daily doses should be reduced in patients with impaired kidney function. High doses in the elderly may cause dizziness, tiredness, and, rarely, confusion. Cimetidine, nizatidine or ranitidine may cause breast enlargement in men (gynacomastia).

Proton-pump Blockers

Esomeprazole (Nexium), lansoprazole (in Heliclear, Zoton), omeprazole (Losec), pantoprazole (Protium) and rabeprazole (Pariet) block the production of acid in the stomach and are useful for treating peptic ulcers and acid reflux, and also ulcers caused by non-steroidal anti-inflammatory drugs. They are the treatment of choice for gastro-oesophageal reflux disease (GORD). They produce more rapid ulcer healing than the H₂ blockers and are more effective in GORD and reflux oesophagitis. They may cause diarrhoea, skin rash and headache.

3. Drugs which Protect the Stomach Lining

Liquorice wood has been used in various herbal indigestion mixtures for centuries. But when in 1948 crude powdered liquorice extract was tried in patients suffering from peptic ulcers it was found that one in five developed serious adverse effects which included high blood pressure, irregular heart-beats and muscle weakness.

Carbenoxolone improves mucosal defence. It is a less toxic derivative of liquorice and is combined with antacids in Pyrogastrone to treat oesophagitis and GORD. It may cause salt and water retention, and a reduction in blood potassium level. This may result in weight gain and swollen ankles, a rise in blood pressure, and heart failure. The low blood potassium may cause muscle weakness. It should not be given to elderly patients or to those with impaired heart, liver or kidney function or raised blood pressure, or to children.

Bismuth chelate (tripotassium dicitrato-bismuthate, De-Noltab). This is a complex bismuth preparation (not a salt) which forms a protective layer over the ulcer lining. It is active only when the stomach contents are acid. It is effective in treating stomach and duodenal ulcers. Ulcer healing may be helped by elimination of  bacteria that are associated with peptic ulcers (Helicobacter pylori). It has an ulcer healing rate similar to cimetidine with a lower relapse rate. However, it causes darkening of the tongue, nausea and vomiting, and should not be used as long-term treatment. It should not be used in pregnancy or in patients with impaired kidney function.

Sucralfate (Antepsin) protects the ulcer lining from acid and pepsin attack. It is a complex of aluminium hydroxide and sulphated sucrose. It is effective in treating stomach and duodenal ulcers. It also stimulates production of mucus, bicarbonate and prostoglandins to help ulcer healing. Long-term use may be associated with the absorption of aluminium into the blood. It should be used with caution in patients with impaired kidney function.

Misoprostol (Cytotec) is a synthetic prostaglandin that works by stimulating the production of mucus which protects the surface of the stomach, and by stimulating the production of sodium bicarbonate (the stomach’s own antacid). It also decreases acid production and improves the blood supply to the surface of the stomach. All these effects combine to protect the stomach and it is useful for preventing ulceration caused by non-steroidal anti-inflammatory drugs (NSAIDs), used in the treatment of arthritis and joint pain. It is as effective as H₂ blockers in healing duodenal ulcers but less effective in healing gastric ulcers and oesophagitis. It may cause diarrhoea and causes the uterus to contract. It should not be used in pregnancy, or if trying to get pregnant.
Drugs Used to Treat Indigestion and Peptic Ulcers · 85

Healing Peptic Ulcers

The following drugs heal peptic ulcers but they do not cure them. The ulcers may recur when treatment is stopped – H₂ blockers (cimetidine, famotidine, nizatidine, ranitidine), bismuth chelate or sucralfate, a prostaglandin analogue (misoprostol), or a proton-pump blocker (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole).

Curing Peptic Ulcers by eradicating Helicobacter Pylori

The discovery that peptic ulcers are associated with infection by the bacteria Helicobacter pylori has revolutionised peptic ulcer treatment. Treatment to eradicate the infection and cure peptic ulcers involves the use of an ulcer-healing drug combined with antibacterial drugs.

Triple therapy (for one week)

An ulcer-healing drug, lansoprazole, omeprazole, pantoprazole, ranitidine bismuth citrate, plus any two of the following antibiotics: clarithromycin, amoxicillin, metronidazole.

Two week dual therapy regimens using a proton pump inhibitor and a single antibacterial are not recommended because they produce low rates of H. pylori eradication.

Acid Reflux, Oesophagitis, Heartburn, Gastro-oesophageal reflux disease (GORD)

The washing of stomach contents which contain acid and pepsin up into the lower end of the oesophagus (gullet) may produce inflammation of the oesophagus; this is referred to as reflux oesophagitis or gastro-oesophageal reflux disease (GORD). The characteristic symptom is heartburn – a burning pain in the centre of the lower chest after eating a large meal, stooping or lying flat. Reflux oesophagitis is a major cause of indigestion and is linked to smoking, diet and being overweight.

The reflux of acid (acid regurgitation) from the stomach into the oesophagus is caused by a weakness in the circular muscles of the diaphragm that normally close off the top of the stomach from the oesophagus (the gastro-oesophageal sphincter) and prevent swallowed food and drink from coming back up – unless of course you vomit. The reflux of acid up into the oesophagus may be due to a hiatus hernia, which allows parts of the stomach to bulge upwards (herniate) into the opening (hiatus) in the diaphragm through which the oesophagus passes.

General Treatment

Reflux can be reduced by sleeping propped up in bed (use three or four pillows), by avoiding too much bending down and, where appropriate, by stopping smoking, stopping alcohol and losing weight. Regular small, non-fatty meals will help and the amount of tea and coffee drunk should be reduced.

Drug Treatment of Heartburn

Antacids to Neutralize Stomach Acid

Antacids are described earlier. Effective doses will neutralize the acid in the stomach and often provide instant relief from reflux symptoms.  Antacids include:

• aluminium hydroxide (Aludrox (liquid and tablets), Alu-Caps, Actal.
• aluminium hydroxide and magnesium hydroxide (Altacite, Birley, Dijex, Dynese, Entrotabs, Gelusil, Maalox,Maalox TC, Maclean, Moorland, Mucogel).
• calcium (Barum Antacid, Rap-eze, Remegel, Rennies, Settlers, Tums)
• calcium and magnesium (Andrews Antacid, Bisma-Rex, Boots Indigestion, DeWitts Antacid powder and tablets, Opas)
• magnesium (Bismag, Bisodol Indigestion powder and tablets, Carbellon, Magnatol, Phillip’s Milk of Magnesia, Roter)

Additives that Protect the Surface of the Oesophagus

Additives in antacid mixtures aimed at protecting the oesophagus provide additional relief. These additives include alginic acid or one of its salts (alginates) which are obtained from algae. They work as emulsifiers and float to the top of the stomach contents to form a ‘raft’ containing the antacid. This helps to protect the sensitive lining of the oesophagus from the acid in the stomach.

Alginate-containing antacids (raft floating antacids) usually contain less antacid than ordinary antacid preparations, but the raft appears to make them more effective for relieving reflux symptoms. They provide relief in some people.

Another commonly used additive is the silicone dimeticone, which acts as an anti-foaming agent and helps to stop the acid contents of the stomach frothing up into the oesophagus. Activated dimeticone is a mixture of liquid dimeticone containing finely divided silicone dioxide which increases its de-foaming properties. In some people, antacid preparations containing dimeticone provide more relief from reflux symptoms than antacids alone.

Warning: A preparation containing dimeticone should never be taken with a preparation that contains alginic acid or an alginate because their actions oppose each other and the raft provided by the latter would sink.

Antacids Plus a Local Anaesthetic to Relieve Pain

Mucaine is an antacid mixture that contains the local anaesthetic oxethazine. There is doubt about the benefits of using a local anaesthetic for this purpose but some patients experience relief from reflux symptoms.

Drugs that Block Acid Production

H₂ blockers before meals and an alkali/alginic mixture after meals provide good relief from reflux symptoms, but H₂ blockers appear to be less effective at treating peptic ulcers in the oesophagus than in the stomach or duodenum. Treatment should continue for two months.

Proton-pump blockers (e.g. omeprazole) are the drugs of choice for treating severe oesophagitis (see earlier).

Drugs that Affect the Gastro-oesophageal Sphincter

Drugs that close the circular muscle (the gastro-oesophageal sphincter) will prevent the reflux of acid up into the oesophagus. The anti-dopamine drug metoclopramide (Gastrobid, Gastroflux, Maxolon) is an example of these drugs, and it can work very effectively in some people.

Combined Preparations Used to Treat Heartburn

Antacid Preparations Containing Activated Dimeticone

Actonorm (gel and powder), Altacite Plus: co-simalcite (tablets and suspension). Asilone (tablets, gel and suspension), Bisodol Wind Relief (tablets), Boots Double Action Indigestion, Kolanticon (with dicyclomine) Maalox Plus (tablets and suspension), Polycrol (gel and tablets), and Simeco (tablets).

Antacid Preparations Containing Dimeticone

Simeco (suspension), Sovol (suspension).

Antacid Preparations Containing Alginic Acid or an Alginate

Algicon (tablets and suspension), Bisodol Heartburn, Boots Heartburn Relief, Gastrocote (tablets and liquid), Gaviscon (tablets, liquid, infant powder), Peptac (liquid) and Topal (tablets).

Other Preparations

Mucaine (suspension) – antacids with oxetacaine (a local anaesthetic). Nulacin (tablets) – antacids with peppermint oil.

Pyrogastrone (tablets and liquid) – antacids with carbenoxolone (ulcer-healing drug) and sodium alginate.

Drugs Used to Treat Gallstones

The bile acid ursodeoxycholic acid (Destolit, Urdox, Ursofalk, Ursogal) is used to treat patients with mild symptoms, healthy gall-bladders, and small or medium-sized cholesterol gallstones which are radiolucent to X-rays and are not treatable by other means. Patients need to be in hospital and monitored by X-ray and ultrasound, which require hospital supervision. Gallstones recur in one in four patients within one year of stopping treatment. Ursodeoxycholic acid produces diarrhoea less frequently than chenodeoxycholic acid and liver dysfunction has been reported with chenodeoxycholic acid.

Essential oils (e.g. in Rowachol) are sometimes used as additional treatment to dissolve stones in the common bile duct. They claim to dissolve cholesterol stones (radiolucent stones). However, they are only suitable for small stones because they are very slow to work – it may take years to dissolve small stones.