Digestive

Inflammatory bowel diseases

Inflammatory bowel disease (IBD) is a group of disorders caused by chronic inflammation of the intestines. The two most common forms of IBD are Crohn's Disease, which can affect any part of the upper or lower GI tract, and ulcerative colitis that affects only the large intestine or colon and rectum. Both diseases are thought to be autoimmune diseases due to an over-reactive immune system, when the immune system attacks self, in this case, intestinal tissue. Symptoms vary from mild to severe when inflammation flares up with symptoms including, abdominal pain and cramping, rectal bleeding, diarrhoea and vomiting. Medications used for treating IBD to relieve symptoms include:

• Anti-inflammatory drugs like Mesalazine that inhibit the cyclo-oxygenase enzyme (COX) and block the production of inflammatory chemicals like prostaglandins and leukotrienes, which also inhibits the migration of inflammatory cells like macrophages into intestine wall.


• Immunomodifiers like sulphasalazine, which have anti-inflammatory, immunomodulatory and immunosuppressive effects and work by several different mechanisms, including, inhibiting production of inflammatory chemicals like prostaglandins and leukotrienes, which are also involved in immune reactions, influencing white cell function and inhibiting antibody production.


• Corticosteroids like budesonide, which are also anti-inflammatory but work by a different mechanism, binding to a glucocorticosteroid receptor in the intestinal cells and inhibiting the production of inflammatory cytokines and cytokine-mediated immune responses.

Irritable bowel syndrome

Irritable bowel syndrome (IBS) covers a range of functional bowel disorders and includes conditions like chronic irritable colon (spastic colon), spastic constipation, spastic colitis and nervous diarrhoea. IBS has no specific cause but may be triggered by several factors, including food sensitivity, stress and infection. Symptoms are caused by spasm of the intestinal muscle as it squeezes food through the intestine and include abdominal pain and cramps, diarrhoea (with or without alternating constipation) and flatulence (wind). Medications used for treating IBD include:

• Antispasmodics like mebeverine and propantheline that are both anticholinergic and work primarily by blocking the action of the neurotransmitter acetylcholine that is involved in regulating intestinal smooth muscle contraction. This action allows the smooth muscle to relax, reducing muscle spasm.


• Serotonin agonists like tegaserod that also regulate intestinal smooth muscle contraction by binding to specific serotonin receptors found only in the nerve cells of the GI tract and this helps restore normal bowel motility; it also helps reduce sensitivity to pain and discomfort caused by symptoms of IBS.

Constipation

Chronic constipation may be a symptom of several GI disorders and is characterised by hard stools that are difficult to pass and infrequent bowel movements. Laxatives like lactulose help soften the stools by changing the osmotic pressure in the colon and allowing water to be drawn into the colon, which also increases bowel motility and makes the stools easier to pass.

Peptic ulcers and reflux

Gastric acid is needed for digestion of food. Gastric reflux or gastroesophageal reflux disease (GORD) is when the acidic contents of the stomach flow back into the oesophagus causing heartburn (a burning feeling from the stomach towards the neck) and dyspepsia (indigestion and abdominal pain). Reflux disease, as this condition is commonly known, is usually due to damage or loss of normal function of the sphincter muscle at the junction of the oesophagus and stomach that normally acts as a one-way valve and prevents backflow of stomach contents. Reflux can also damage the oesophagus causing oesophagitis or inflammation of the oesophagus.

Peptic ulcers are damage to the stomach lining (gastric ulcers) or the lining of the upper intestine (duodenal ulcers) and are caused by excess gastric acid production due to use of nonsteroidal anti-inflammatory drugs (NSAID) or by infection of the stomach with the bacterium Helicobacter pylori.

Medications used to treat reflux and ulcers are based on reducing the amount of gastric acid produced and released into the stomach, and fall into two categories:

• Proton pump inhibitors like omeprazole, esomeprazole, rabeprazole and lansoprazole, which block the enzyme involved in producing gastric acid by stomach lining cells.
• H2-receptor antagonists like ranitidine, which block the gastric H2-receptor preventing the normal stimulation by histamine of gastric acid production.

Ulcer protection

Another treatment for peptic ulcers is using a cytoprotectant like sucralfate that forms a protective barrier over the ulcer from the damaging effects of gastric acid and digestive enzymes.

Gastroparesis

Gastroparesis is when the stomach muscles do not work properly causing a partial paralysis of the stomach and delayed emptying of the contents. The result is that food stays too long in the stomach before emptying into the small intestine and this can put extra pressure on the esophageal sphincter. Gastroparesis is usually due to nerve damage and can be treated using a serotonin (5HT) receptor agonist like cisapride. This action stimulates stomach muscle contraction so that food can be moved out into the small intestine.

Stomach muscle spasm

Muscle spasm in the stomach can be caused by a variety of GI disorders, including peptic ulcers, reflux disease, infection or food intolerance. Muscle spasm can be treated symptomatically using an antispasmodics medication like propantheline that works as an anticholinergic by blocking the action of the neurotransmitter acetylcholine that is involved in regulating intestinal smooth muscle contraction. This action allows the smooth muscle to relax, reducing muscle spasm.

Nausea

Nausea and vomiting are symptoms of several different conditions, including, gastrointestinal disorders, migraine, chemotherapy and radiotherapy for cancer treatment, reaction to surgical anaesthetic and dysmobility, which is when the intestinal or stomach muscles do not work efficiently and movement of food through the GI tract slows down. The vomiting reflex originates in the chemoreceptor trigger zone (CTZ) of the area postrema of the brain sending nerve messages to the vomiting centre of the brain. Medications used to relieve nausea and vomiting include two types of antiemetic:

• Serotonin receptor-antagonists like ondansetron that work by binding to specific 5HT3 receptors in the intestine and in the CTZ and block the transmission of nerve messages from the intestines and from the CTZ to the vomiting centre in the brain, which prevents the vomiting reflex from being triggered.
• Dopamine antagonist like domperidone and metoclopramide that work by binding to dopamine receptors in the CTZ blocking the transmission of nerve messages to the vomiting centre in the brain, which prevents the vomiting reflex from being triggered. They also have gastrokinetic action by interacting with nervous control of muscle contraction in the stomach and upper intestine, which helps relieve symptoms of dysmobility (when food processing slows down) and this also helps prevent vomiting.