Gastrointestinal system

Laxative drugs

Laxatives are used to treat constipation (defined as passing hard stools less frequently than normal for the patient). The aetiology of constipation is varied and can be a symptom of organic disease, or can be a side effect of certain drug treatments (e.g. opioid-induced constipation, OIC). Laxatives are of clinical value in the treatment of irritable bowel syndrome (IBS), OIC, as part of anthelmintic treatment or to clear the alimentary tract before surgery and radiological procedures. Abuse of laxatives may lead to hypokalaemia.

The mechanism of action of laxatives is varied, being physical or biochemical in nature:

Bulk-forming laxatives improve stool formation by adding bulk to the diet. This group includes wheat bran-based dietary supplements, methylcellulose, ispaghula husk and sterculla. Bulk-forming laxatives are useful in the management of IBS, chronic diarrohea associated with diverticular disease, and in patients with colostomy, ileostomy, haemorrhoids and anal fissure. Can also be used as an adjunct in the treatment of ulcerative colitis.

Stimulant laxatives for example, bisacodyl, sodium picosulphate, anthroquinines such as senna, and parasympathomimetics such as bethanechol chloride (a muscarinic cholinergic receptor agonist), neostigmine and pyridostigmine bromide (both acetylcholinesterase inhibitors) increase intestinal motility. Over use can cause diarrohea and hypokalaemia.

Faecal softeners ease the passage of stool in the gut. Bulk-formaing laxatives, non-ionic surfactant agents, glycerol and arachis oil all have softening properties.

Osmotic laxatives commonly contain polyethylene glycol (PEG) or salts as the active ingredient. These agents increase water in the large intestine to soften the stool and promote bowel movement. High-dose saline preparations are often used as bowel clearing agents prior to colonoscopy, colonic surgery or radiological examination.

Other laxative drugs include linactolide (an oral guanylate cyclase C receptor agonist, see Busby et al. (2010)), lubiprostone (a chloride channel activator) and prucalopride (a serotonin 5HT4 receptor agonist).

 

Antisecretory drugs

In the gastrointestinal system, anti-secretory drugs are used to decrease acid secretion in the stomach.

Drug families include:

Histamine H2 receptor antagonists are used to treat functional dyspepsia and to promote healing of NSAID-associated ulcers e.g. ranitidine, cimetidine and famotidine.

Proton pump inhibitors (PPIs) are used to treat gastric and duodenal ulcers, dyspepsia, gastro-oesophageal reflux disease (GERD) and NSAID-associated ulcers. Combined with antibacterials, PPIs are used to eradicate Helicobacter pylori infection. Can also be used to reduce the degradation of pancreatic enzyme supplements in cystic fibrosis patients, and to control excessive gastric acid production in Zollinger–Ellison syndrome. Examples are omeprazole and its single active enantiomer esomeprazole, lansoprazolerabeprazole and pantoprazole. Infrequently, patients taking PPIs have been reported to be suffering from drug-induced subacute cutaneous lupus erythematosus (SCLE), so prescribers should be aware of this rare side-effect and consider discontinuing PPI treatment if feasible.

The Prostaglandin analogue misoprostol is approved for treatment of gastric and duodenal ulceration and NSAID-associated ulceration and prophylaxis of NSAID-induced gastric and duodenal ulcers.

Antimuscarinic drugs such as the muscarinic M1 receptor antagonist pirenzepine were used to treat peptic ulcer, but are no longer widely used.

Mucosal protectants such as sucralfate may be used to manage benign gastric and duodenal ulceration and chronic gastritis, and as a prophylactic for stress-induced ulcers. Sucralfate aids healing by forming a viscous, protective layer on the ulcer's surface, but does not prevent new ulcer formation.

Antidiarrhoeal drugs

Antidiarrhoeal drugs are classified according to their mechanism of action:

Oral rehydration agents are used to re-balance fluid and electrolytes lost during a diarrhoeal episode. These contain defined quantities of salts and sugars to be taken with clean water.

Antibacterial agents can be used to treat diarrhea with a confirmed bacterial cause.

Antimotility agents, or antipropulsives, are used to slow intestinal transit. For example, the opioid analogue loperamide (sold as Imodium®) slows peristalsis and reduces overall stool mass (often combined with the anti-foaming agent simeticone in the brand Imodium Plus®). Diphenoxylate is another opioid analgesic used with atropine (Lomotil®) as an antimotility agent.

Antispasmodic agents are used to reduce the pain and cramping that can accompany diarrhea. For example mebeverine, sold as Colofac® in the UK.

Antispasmodic drugs

Antispasmodic drugs are used to reduce the pain and cramping that can accompany conditions such as irritable bowel syndrome (IBS) and diverticular disease. For example mebeverine, sold as Colofac® in the UK, and scopolamine butylbromide (a.k.a. hyoscine butylbromide or butylscopolamine) sold under the trade name Buscopan.

Antacids

Antacids are used to relieve symptoms in dyspepsia and in gastro-oesophageal reflux disease and usually contain aluminium or magnesium compounds. They should be given when symptoms occur or are expected, usually between meals and at bedtime. They may have to be given several times each day. Although they may help with ulcer-healing, their impact is much less than for antisecretory drugs. Liquid preparations are usually more effective than tablet preparations.

Aluminium- and magnesium-containing antacids (e.g. aluminium hydroxide, and magnesium carbonate, hydroxide and trisilicate), being relatively insoluble in water, are long-acting if retained in the stomach. They are suitable for most antacid purposes. Magnesium-containing antacids tend to be laxative whereas aluminium-containing antacids may be constipating; antacids containing both magnesium and aluminium may reduce these colonic side-effects. Aluminium accumulation does not appear to be a risk if renal function is normal.

Sodium bicarbonate should no longer be prescribed alone for the relief of dyspepsia but it is present as an ingredient in many indigestion remedies. It is still used to treat urinary-tract disorders and acidosis. Sodium bicarbonate contains a significant salt load and should be avoided in patients who may retain this.  

Bismuth-containing antacids are not recommended because absorbed bismuth can be neurotoxic and lead to encephalopathy.

Calcium-containing antacids can induce rebound acid secretion: with modest doses the clinical significance is doubtful, but prolonged high doses also cause hypercalcaemia and alkalosis, and can precipitate the milk-alkali syndrome.

Simeticone (activated dimeticone) is added to an antacid as an antifoaming agent to relieve flatulence. These preparations may be useful for the relief of hiccup in palliative care. 

Alginates, added as protectants, may be useful in gastro-oesophageal reflux disease. The amount of additional ingredient or antacid in individual preparations varies widely, as does their sodium content, so that preparations may not be freely interchangeable.