The drug cimetidine was launched in 1976, as a successful medication to treat peptic ulcers. Over many centuries peptic ulcer has been a major cause of death, at any particular time about 4 million people are effected with peptic ulcer, and the at least 6000 people die from this disease each year.
Peptic ulcer results from erosion within the walls three particular areas of the gastrointestinal tract (GIT); the oesophagus, the stomach or the duodenum. This is due to the excessive production of stomach acid, consisting of hydrochloric acid (HCl) and the enzyme pepsin, required for digestion in the gastrointestinal tract; this can also lead the acid to reach the oesophagus. Under normal circumstances the linings are protected from the irritation of the acidity via the formation of a mucus and bicarbonate barrier. However obstruction of the lining causes inflammation of the mucous membrane and leads to ruptures of the internal tissue.
Such factors as increased consuming of alcohol, smoking, chewing tobacco and radiation treatments can increase the risks of developing peptic ulcers. Thus following diagnosis, patients are advised to cut down on smoking and drinking alcohol, and also to increase regular intakes of small meals.
Patients suffering from peptic ulcers experience upper abdominal pain, heart burns, sleep disturbance, hunger, empty feeling in stomach, unable to drink too much fluid, chest pain, nausea and weight loss. But lack of treatment may lead to internal bleeding; seen by patients vomiting blood and therefore may become fatal resulting in death.
Hence the aims of the treatment are to reduce acid levels. During the earlier days the main treatment was to administer alkali based medications to neutralise the acid production, but this only gave temporary relief. Hence the last resort of treatment was to undergo surgery, removing parts of their stomach. However, following surgery the symptoms associated with ulcers were not cured. This lead to further understanding of the causes of peptic ulcers, and that the regular use of NSAIDs medications such as aspirin to treat other illnesses induces ulcers (figure 2).
Aspirin inhibits the enzyme COX – 1 which normally converts arachidonic acids to prostaglandins. Prostaglandins are responsible for the positive feedback on non parietal cells to produce mucus and bicarbonate protective layers and they show negative feedback on parietal cells, inhibiting acid secretion. Thus inhibition of the COX-1 inhibits synthesis of prostaglandins hence decreased mucus and bicarbonate production and increased acid production (figure 1).
Cimetidine treatment for NSAIDs/aspirin induced acid production was discovered upon investigating histamine receptors located on the parietal cells. Histamine receptor activation, triggers acid secretion, consequently, antagonising the histamine receptor decreases the gastric acid production; thus aiming to treat peptic ulcers.
This discovery was initiated by...