Class of drug	Drug	Dose
H₂-receptor antagonists	Cimetidine	400 mg twice daily
	Famotidine	40 mg daily
	Nizatidine	300 mg daily
	Ranitidine	300 mg daily
Proton pump inhibitors	Esomeprazole	20 mg daily
	Lansoprazole	30 mg daily
	Omeprazole	20 mg daily
	Pantoprazole	40 mg daily
	Rabeprazole	20 mg daily
Antacids	Aluminium hydroxide	10–20 mL 3 times daily
	Magnesium carbonate	10 mL 3 times daily
	Magnesium trisilicate	10–20 mL 3 times daily
	Aluminium and magnesium complexes	10 mL between meals and at bedtime
Others	Alginates and antacids	2 tablets twice daily
Others	Chelates and complexes, e.g. tripotassium, dicitratobismuthate, sucralfate	2 tablets twice daily

Nausea and vomiting

Many gastrointestinal conditions are associated with vomiting, but nausea and vomiting without abdominal pain are frequently non-gastrointestinal in origin, e.g. acute infections, CNS disease and drug ingestion.

• Early-morning vomiting is seen in pregnancy, alcohol dependence and in some metabolic disorders (e.g. uraemia).

• Large volumes of vomit suggest intestinal obstruction; faeculent vomit suggests low intestinal obstruction or the presence of a gastrocolic fistula, while projectile vomiting is due to gastric outflow obstruction.

• Chronic nausea and vomiting with no other abdominal symptoms usually have a psychological cause.

Treatment

Many patients require no therapy. Food is usually withheld and fluids only are allowed. With more persistent vomiting, IV fluids, e.g. 0.9% saline (p. 369), are given for dehydration and correction of electrolyte abnormalities. A naso-gastric tube is inserted if there is bowel obstruction.

• Hyoscine 300 mcg is the most effective drug for motion sickness.

• Antihistamines, e.g. cyclizine 50 mg oral/IM/IV 3 times daily, oral cinnarizine 15 mg and oral promethazine 25–75 mg, are also used for motion sickness and in nausea and vomiting with vertigo. Drowsiness and antimuscarinic side-effects, such as urinary retention, dry mouth, photophobia (dilatation of the pupil), confusion and constipation (p. 137), occur.

• Dopamine receptor antagonists

• Phenothiazines, e.g. prochlorperazine 10 mg oral 3 times daily, perphenazine 4 mg 3 times daily oral, trifluoperazine 2–4 mg oral in divided doses and chlorpromazine 10–25 mg orally 4–6-hourly, are useful for vomiting produced by drugs or surgery and in nausea associated with vertigo. Drowsiness, acute dystonic reactions and other extrapyramidal side-effects occur.

• Metoclopramide is given 10 mg 3 times daily orally or intravenously for all causes of vomiting, with high doses often given by intravenous infusion for cytotoxic drug-induced vomiting. It is a pro-kinetic agent with additional central effects.

• Domperidone 10 mg 3 times daily oral is predominantly used for cytotoxic drug-induced vomiting. It has few central effects, as it does not cross the blood–brain barrier easily. Side-effects of metoclopramide and domperidone include sedation and acute dystonia, although dystonia is less with domperidone. Both drugs should be avoided in pregnancy.

• Serotonin (5HT₃) antagonists are mainly used for cytotoxic drug-induced vomiting and post-operatively. Granisetron 1–2 mg is given 1 hour before cytotoxic treatment, then 2 mg daily. Ondansetron is given as 8 mg 1–2 hours before treatment, then 8 mg every 12 hours. Side-effects include constipation, headache and rash.

• Synthetic cannabinoid (nabilone 1 mg twice daily) is used for cytotoxic-induced vomiting refractory to other treatments. Side-effects include drowsiness, ataxia (these two can persist for 72 hours) and visual disturbance. Avoid in patients with a history of psychiatric disorder and in the elderly.

• Neurokinin receptor antagonist (aprepitant 125 mg 1 hour before chemotherapy, then 80 mg daily for 2 days) is used as an adjunct to dexamethasone and 5HT₃ treatment. Side-effects include gastrointestinal problems, headaches and dizziness. Do not use when the patient is breast-feeding.

Diarrhoea

Acute diarrhoea

Acute diarrhoea is very common and is usually due to dietary indiscretion, infectious agents, toxins or drugs, e.g. antibiotics, magnesium-containing antacids, or laxatives. It is usually self-limiting and ceases in 24–48 hours with no treatment.

• Watery diarrhoea. Viral infections with rotavirus, enteric adenovirus and norovirus are common and usually cause acute watery diarrhoea. Salmonella, Campylobacter and non-invasive Escherichia coli and Clostridium difficile may also cause watery diarrhoea.

• Bloody diarrhoea (dysentery). This can occur due to Shigella, Campylobacter, Salmonella, invasive E. coli subtypes and C. difficile.

• Investigations

• Stool culture. Salmonella, Shigella, Campylobacter and E. coli can all be detected on culture. Detection of viral particles requires electron microscopy, which is not performed routinely.

• Ova, cysts and parasites. Amoebiasis and giardiasis should be considered in returning travellers with diarrhoea.

• C. difficile toxin. C. difficile infection is associated with the use of broad-spectrum antibiotics and is a common cause of diarrhoea in hospitalized patients. It is diagnosed by the presence of toxin in stools.

• Flexible sigmoidoscopy. This may be useful in protracted cases to allow mucosal assessment and biopsy.

• Oral rehydration solutions (p. 59) containing glucose and electrolytes are useful to prevent dehydration. IV rehydration is generally required only in severe cases or in the very young and very old.

• Antidiarrhoeal drugs may impair clearance of the pathogen but can be given for symptomatic relief.

• Loperamide 2–4 mg 4 times daily is a non-absorbed opioid that stimulates receptors in the enteric nervous system to reduce peristalsis and fluid secretion. It has the advantage of being non-euphoria-inducing, has no antimuscarinic side-effects and dependence does not occur. Adverse effects include nausea.

• Codeine 30–60 mg oral 4 times daily acts in a similar way to loperamide but is systemically absorbed; opioid side-effects occur.

• Co-phenotrope 2 tablets 4 times daily contains an opioid (diphenoxylate) and an antimuscarinic agent (atropine) which reduces colonic motility. It has antimuscarinic side-effects (p. 134).

All produce constipation if given frequently.

• Specific therapy

• Antibiotic therapy. Most bacterial causes of diarrhoea are self-limiting (lasting only days) and antibiotics are not necessary. Quinolones (e.g. ciprofloxacin 500 mg twice daily) may decrease the severity and duration of symptoms.

• C. difficile. A course of 10–14 days of oral metronidazole 400 mg 3 times daily. Oral vancomycin 125 mg 4 times daily is used for resistant cases. Oral vancomycin and IV metronidazole are used in patients not responding to vancomycin and with life-threatening infections.

• Amoebiasis. Diagnosis is confirmed by the presence of trophozoites or cysts of Entamoeba histolytica in the stool, or by serum antibody tests. Treatment is with oral metronidazole 800 mg 3 times daily for 5–10 days or tinidazole oral 2 g daily for 2–3 days. Oral paromomycin 500 mg 3 times daily for 7 days or oral diloxanide furoate 500 mg 8-hourly for 10 days should be given to clear parasites from the bowel.

• Giardiasis. Diagnosis is clinical. Trophozoites of Giardia intestinalis in stool or duodenal aspirate are not usually found. Therapy consists of oral metronidazole 2 g a day for 3 consecutive days or tinidazole 2 g orally single dose.

Diarrhoea in patients with HIV infection

Chronic diarrhoea is a common symptom in patients with HIV infection (p. 96). Cryptosporidium is the commonest pathogen isolated. Other infective causes include cytomegalovirus, Mycobacterium avium and Giardia intestinalis. Stool culture with examination for ova, cysts and parasites should be performed, together with flexible sigmoidoscopy/colonoscopy and biopsy.

• Treatment should be directed at individual causes. Some suggest empiric therapy with metronidazole for Giardia. Non-infective causes of diarrhoea associated with HIV disease include a specific enteropathy, lymphoma and Kaposi’s sarcoma. All these conditions are less common with highly active anti-retroviral treatment (HAART).

Chronic diarrhoea

Chronic diarrhoea refers to diarrhoea of more than 4 weeks’ duration. It can be due to a variety of causes (usually non-infective) including inflammation (inflammatory bowel disease), drugs (metformin, statins), functional factors, malabsorption or cancer (change in bowel habit), the treatments for which are described elsewhere.

• Clinical features

• Steatorrhoea suggests excessive fat in the stool and is due to malabsorption and pancreatic disease.

• Bloody diarrhoea suggests active colonic inflammation and is most commonly due to inflammatory bowel disease.

• Watery diarrhoea is the most common presentation and encompasses the broadest range of diagnoses. When standard investigations have proved unhelpful, a 72-hour assessment of stool weights may be helpful. The stool weights per day are not normally performed but in general: < 250 g is normal (frequency of defecation is often interpreted as diarrhoea by patients with, for example, irritable bowel syndrome); between 300 and ∼800–900 g is probably organic (Crohn’s disease); > 1000 g may be due to laxative abuse or a neuroendocrine tumour, e.g. VIPoma, causing profuse watery diarrhoea.

• Investigations. These include rectal examination, sigmoidoscopy, stool culture and ova, cysts and parasites, followed by a colonoscopy or barium follow-through, depending on type of diarrhoea. Small bowel MRI is replacing barium follow-throughs.

• Treatment. Treatment is usually directed at the cause, but symptomatic treatment as above is appropriate whilst investigations are ongoing or when specific therapy has failed to provide relief.

Constipation

This term is used for the infrequent passage of stool (< 2 per week), straining > 25% of the time or passage of hard stools and incomplete evacuation. Headache, malaise, halitosis, abdominal bloating and discomfort are often attributed to constipation without any factual evidence.

Constipation can come on acutely and, in the older patient, may indicate an organic disorder. Chronic constipation lasting years is usually functional.

Local anal diseases, e.g. fissures or haemorrhoids, are associated with constipation, as are some drugs, e.g. opiates, antimuscarinics, calcium channel blockers (such as verapamil), antidepressants and iron, and systemic disorders, e.g. hypothyroidism, hypercalcaemia and diabetes mellitus.

Rectal examination, flexible sigmoidoscopy/colonoscopy or CT pneumocolon (barium enema is being used less) may be necessary to rule out structural diseases in recent-onset constipation.

Treatment

• Lifestyle changes. Lifestyle changes, including a high fluid intake and regular exercise, help. Dietary fibre is mainly non-starch polysaccharides (NSP), which are soluble or insoluble. Soluble fibre (e.g. psyllium, ispaghula, calcium polycarbophil — found in the flesh of fruits, vegetables and grains) is broken down and fermented by colonic bacteria, increasing stool bulk. Insoluble fibre (wheat bran, corn) also increases the bulk of stools but can sometimes make symptoms worse, e.g. wind. Dietary fibre should be increased to up to 30 g a day. This is achieved by increasing consumption of bread, potatoes, fruit and vegetables and reducing sugar intake in order to avoid an increase in total calories. Unprocessed bran added to food increases fibre but many find it unpalatable. Bulk-forming laxatives increase faecal mass, which stimulates peristalsis, and are of use in those individuals with small hard stools where dietary fibre cannot be sufficiently increased. Ispaghula husk 3.5 g twice daily or methylcellulose 1.5–3 g twice daily is used.

• Laxatives (Box 5.2)

• Osmotic laxatives are non-absorbable salts or carbohydrates that increase the amount of water retained in the large bowel and should be used as first-line drugs. Lactulose 15 mL twice daily is a semi-synthetic non-absorbed disaccharide. As a side-effect it can cause cramps and flatulence. Macrogols, inert polymers of ethylene glycol (1–3 sachets daily), are not fermented so gas is not formed and distension does not occur. Magnesium salts 5–10 g daily are dissolved in a glass of hot water before breakfast; they work in 2–4 hours.

• Stimulant laxatives increase intestinal motility and can consequently cause abdominal cramps. They are contraindicated in intestinal obstruction. Benign pigmentation of the colon (melanosis coli), colonic atony due to smooth muscle atrophy and damage to the myenteric plexus occur and so these drugs should not be used long-term. Bisacodyl 5–10 mg at night (tablets or suppositories), or dantron –co-danthrusate 1–2 capsules at night is indicated only in terminally ill patients (because of evidence of carcinogenicity in animal studies). Senna is given as 15–30 mg at night and increasing gradually.

• Lubiprostone is a bicyclic fatty acid, which opens chloride channels, increasing intestinal water secretion. It is used in the irritable bowel syndrome with constipation.

• Methylnaltrexone is an opioid antagonist and is effective in opioid-induced constipation without reducing the analgesic effect. It is given subcutaneously.

• Faecal softeners (e.g. liquid paraffin) can be given and arachis oil per rectum helps to soften impacted faeces.

• Bowel-cleansing solutions are used as pre-operative or pre-procedural regimens to empty the bowel. They should not be used routinely as laxatives. They are used in combination with a low-residue diet for the 48 hours prior to the procedure. They include sodium picosulphate 10 mg sachets; 2 sachets on the day before the procedure; a mixture of macrogols, sodium sulphate and bicarbonate 4 L 4–6 hours before the procedure; and magnesium carbonate mixture 2 sachets on the day before the procedure. Very elderly patients must be observed to avoid dehydration.

• Prucalopride is now used for resistant constipation.

• Biofeedback. For some patients chronic constipation is due to a failure of coordination of the process of defecation. Biofeedback has been shown to be of benefit in these patients and is used in some specialized centres.

Gastro-oesophageal reflux disease

Reflux is extremely common in the general population, causing mild indigestion and heartburn.

Heartburn is the major feature and is mainly due to direct stimulation of the hypersensitive oesophageal mucosa, but also partly caused by spasm of the distal oesophageal muscle. It is aggravated by bending, stooping or lying down and may be relieved by antacids. The patient may complain of a burning pain on drinking hot liquids or alcohol.

Regurgitation of food and ‘acid’ into the mouth occurs, particularly when the patient is bending or lying flat. Aspiration into the lungs, producing pneumonia, is unusual without an accompanying stricture, but cough and nocturnal asthma from regurgitation and aspiration can occur. The differential diagnosis of the retrosternal pain from angina can be difficult; 20% of cases admitted to a coronary care unit have gastro-oesophageal reflux disease (GORD).

• Prokinetic agents metoclopramide 10 mg 3 times daily and domperidone 10 mg 3 times daily are dopamine antagonists (for side-effects, see p. 644). They are occasionally helpful, as they enhance peristalsis and speed gastric emptying. Cisapride has been withdrawn because it increases the Q–T_c interval and the risk of arrhythmias.

• Surgery. Surgery should never be performed for a hiatus hernia alone. The properly selected case with severe reflux symptoms confirmed by pH monitoring and with oesophagitis on oesophagoscopy responds well to surgery. Repair of the hernia and additional antireflux surgery (e.g. a modified Nissen fundoplication) is performed laparoscopically. Results show an improvement in symptoms in up to 80% of cases. The indications for surgery are not always clear, as medical therapy with PPIs is so effective; a young patient requiring years of drug treatment is one common indication. Patients with oesophageal dysmotility unrelated to acid reflux do less well than those with proven reflux.

Non-erosive reflux disease (NERD)

These cases include patients with reflux symptoms. They often do not respond to a PPI. Patients are usually female and often the symptoms are functional (p. 167).

Complications

• Peptic stricture usually occurs in patients over the age of 60. The symptoms are those of dysphagia over a long period preceded by severe heartburn. Treatment is by dilatation of the stricture and a PPI is given to achieve anacidity. Occasionally, surgery for continued reflux is required. Intermittent dysphagia is more classical of a Schatzki ring than a peptic stricture.

• Barrett’s oesophagus. This occurs as a result of longstanding reflux (Fig. 5.1). It consists of columnar epithelium with intestinal metaplasia extending upwards into the lower oesophagus and replacing normal squamous epithelium. Barrett’s oesophagus (even short segment < 3 cm) is pre-malignant for adenocarcinoma. Risk factors for progression are male sex, age > 45 years, length of segment > 8 cm, early age of onset and duration of symptoms of GORD, the presence of ulceration and stricture and a family history. Dysplasia is patchy and biopsies from all four quadrants (every 2 cm) of the Barrett’s segment must be performed. There is some evidence that anti-reflux surgery leads to Barrett’s regression. Patients without dysplasia do not require surveillance. Low-grade dysplasia requires regular endoscopic surveillance. High-grade dysplasia is now treated with radiofrequency ablation using the HALO system or local endomucosal resection. Endoscopic ablation therapy with photodynamic therapy or laser is also used.

• Adenocarcinoma. Patients with weekly reflux symptoms were nearly 8 times more likely to develop adenocarcinoma than those without symptoms in one study. The greater the frequency, severity and the duration of reflux symptoms, the greater the risk.