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Therapeutics 63
Side effects
Hypersensitivity reactions include urticaria, fever, rashes and anaphylaxis.
Individuals with a history of anaphylaxis, urticaria or rash immediately
after penicillin administration are at risk of immediate hypersensitivity to a
penicillin and should not receive a penicillin or cephalosporin (10% of penicillin-allergic patients are also allergic to cephalosporins). Encephalopathy
with fits results from excessively high doses or in patients with severe renal
failure. Diarrhoea and C. difficile infection (p. 40) can occur as a result of
disturbance of the normal colonic flora. Other effects are interstitial nephritis, hepatitis, cholestatic jaundice, reversible neutropenia and eosinophilia.
Aminopenicillins (e.g. amoxicillin) frequently produce a non-allergic maculopapular rash in patients with glandular fever.
Cautions/contraindications
Contraindicated in penicillin hypersensitivity (see above); macrolides are an
alternative in these patients.
Cephalosporins
Cephalosporins are often classified by ‘generations’ (e.g. first generation,
cefalexin; second generation, cefuroxime; third generation, cefotaxime).
The members within each generation share similar antibacterial activity.
Succeeding generations tend to have increased activity against Gram-negative
bacilli, usually at the expense of Gram-positive activity, and increased ability
to cross the blood–brain barrier.
Mechanism of action
Cephalosporins inhibit bacterial wall synthesis in a manner similar to the
penicillins.
Indications
Broad-spectrum antibiotics – used for treatment of septicaemia, pneumonia,
meningitis, biliary tract infections, peritonitis and urinary tract infections.
Side effects
Skin rashes, nausea and vomiting, diarrhoea (including C. difficile colitis),
hypersensitivity reactions (see penicillin).
Cautions/contraindications
Penicillin hypersensitivity other than with a minor rash only.
Aminoglycosides
Mechanism of action
Aminoglycosides (e.g. gentamicin, neomycin, streptomycin) inhibit protein
synthesis in bacteria by binding irreversibly to the 30 S ribosomal unit. This
inhibits translation from mRNA to protein. Aminoglycosides are bactericidal.
64 Infectious diseases
Indications
Aminoglycosides are active against many Gram-negative bacteria (including Pseudomonas species) and some Gram-positive bacteria but are
inactive against anaerobes. Aminoglycosides are often used for serious
Gram-negative infections when they have a complementary and synergistic
action with agents that disrupt cell wall synthesis (e.g. penicillins).
Side effects
Aminoglycosides require monitoring of serum concentrations (peak and
trough levels) in all patients with a dose reduction in renal impairment. Most
unwanted effects are dose related and are probably related to high trough
concentrations of the drug. Ototoxicity can lead to both vestibular and auditory dysfunction, which result in often irreversible disturbances of balance or
deafness. Other side effects are renal toxicity, acute neuromuscular blockade,
nausea, vomiting, rash and antibiotic-associated colitis.
Cautions/contraindications
Aminoglycosides are contraindicated in myasthenia gravis. Caution is necessary with dose reduction and frequent monitoring of serum concentrations in
patients with renal impairment.
Macrolides
Mechanism of action
Macrolides interfere with bacterial protein synthesis by binding reversibly to
the 50 S subunit of the bacterial ribosome. The action is primarily bacteriostatic unless at high concentrations.
Indications
Erythromycin has an antibacterial spectrum that is similar to that of penicillin;
it is thus an alternative in penicillin-allergic patients. Indications for erythromycin include respiratory infections, whooping cough, Legionnaires’ disease,
Chlamydia infections and Campylobacter enteritis. Erythromycin has poor
activity against H. influenzae. Clarithromycin is a derivative of erythromycin
with slightly greater activity. Azithromycin has slightly less activity than
erythromycin against Gram-positive bacteria but enhanced activity against
Gram-negative bacteria.
Side effects
Gastrointestinal upset (epigastric discomfort, nausea, vomiting and diarrhoea)
is common with the oral preparation of erythromycin; azithromycin and
clarithromycin are better tolerated. Skin rashes, cholestatic jaundice (with
erythromycin) and prolongation of the QT interval may occur. Erythromycin
and clarithromycin inhibit P450 drug-metabolizing enzymes and can elevate
Therapeutics 65
levels of drugs (e.g. carbamazepine and ciclosporin) requiring these enzymes
for metabolism (see National Formulary for list).
Metronidazole
Mechanism of action
A toxic metabolite inhibits bacterial DNA synthesis and breaks down existing
DNA. Only some anaerobes and some protozoa contain the enzyme (nitroreductase) that converts metronidazole to its toxic metabolite. It is bactericidal.
Indications
Anaerobic infections, protozoal infections, Helicobacter pylori eradication,
C.difficile colitis. Metronidazole is more commonly used than tinidazole.
Side effects
Nausea, vomiting, metallic taste, disulfiram-like reaction (unpleasant hangover symptoms) with alcohol, skin rashes, and abnormal liver biochemistry.
With prolonged therapy, peripheral neuropathy, transient epileptiform seizures
and leucopenia can occur.
Cautions/contraindications
Caution with alcohol ingestion; reduce dose in severe liver disease and avoid
in porphyria.
Quinolones
Mechanism of action
Quinolones (e.g. ciprofloxacin) inhibit replication of bacterial DNA. The effect
is bactericidal.
Indications
Ciprofloxacin has a broad spectrum of activity and is particularly active
against Gram-negative bacteria. It has only weak activity against streptococci, staphylococci and anaerobes.
Side effects
Gastrointestinal upset (nausea, vomiting, diarrhoea), CNS effects (dizziness,
headache, tremors, rarely convulsions), photosensitive skin rashes, tendon
damage (pain, inflammation, rupture).
Cautions/contraindications
Contraindicated in patients with a history of tendon disorders related to quinolone use; risk of tendon rupture is increased by corticosteroids. If tendonitis
is suspected, stop quinolone immediately.
Gastroenterology and
3
GASTROENTEROLOGY
Gastrointestinal (GI) symptoms are a common reason for attendance in primary care and hospital clinics. The differential for these symptoms is wide
and will differ between countries, but clinicians should be aware that 20% of
all cancers occur in the gastrointestinal tract. In developing countries infection is a more common diagnosis.
SYMPTOMS OF GASTROINTESTINAL DISEASE
Dyspepsia and indigestion
Dyspepsia is common and describes a range of upper gastrointestinal tract
symptoms, e.g. epigastric pain or burning, nausea, heartburn, fullness and
belching. Patients are likely to use the term ‘indigestion’ for these symptoms.
Dyspeptic symptoms are caused by disorders of the oesophagus, stomach,
pancreas or hepatobiliary system, but the most common cause is functional
dyspepsia. Other causes include peptic ulceration, gastro-oesophageal reflux
disease or rarely a gastro-oesophageal cancer. Investigation and management of dyspepsia is discussed on page 86.
Dysphagia
Dysphagia is difficulty in swallowing and suggests an abnormality in the
physical passage of liquids or solids from the oral cavity through the
oesophagus and into the stomach. The causes are listed in Table 3.1 and
investigation discussed on page 74.
nutrition
Vomiting
Vomiting occurs as a result of stimulation of the vomiting centres in the
medulla. This may result from stimulation of the chemoreceptor trigger zones
or from gut vagal afferents. Vomiting is associated with many gastrointestinal
conditions, but nausea and vomiting without abdominal pain are frequently
non-gastrointestinal in origin, e.g. due to central nervous system (CNS)
disease (e.g. raised intracranial pressure, migraine), excess alcohol, drugs
(especially chemotherapeutic agents), metabolic conditions (e.g. uraemia,
diabetic ketoacidosis) and pregnancy. Persistent nausea and vomiting without
any other symptoms may also be functional in origin (p. 118).
Symptoms of Gastrointestinal Disease 67
Table 3.1 Causes of dysphagia
Disorders of the mouth and tongue Extrinsic pressure
E.g. tonsillitis Mediastinal glands
Neuromuscular disorders Goitre
Pharyngeal disorders
Bulbar palsy
Myasthenia gravis Intrinsic lesion
Oesophageal motility disorders Malignant stricture
Primary oesophageal disease
Achalasia
Other oesophageal dysmotility
Eosinophilic oesophagitis*
Systemic disease
Diabetes mellitus
Chagas’ disease
Scleroderma
*Increasingly apparent cause of dysphagia (? due to discoordination of longitudinal muscle
of the oesophagus), characterized by eosinophil infiltration of the oesophagus and diagnosed
on mucosal biopsies.
Enlarged left atrium
Benign stricture
Oesophageal web or ring
Foreign body
Pharyngeal pouch
Flatulence
Flatulence describes excessive wind, presenting as belching, abdominal distension and the passage of flatus per rectum. It is rarely indicative of serious
underlying disease.
Diarrhoea and constipation
These are common complaints and not usually due to serious disease.
Diarrhoea implies the passage of increased amounts of loose stool (stool weight
>250 g/24 h) (p. 117). This must be differentiated from the frequent passage
of small amounts of stool (that patients often refer to as diarrhoea), which is
commonly seen in functional bowel disorders. Investigation and management
are discussed on page 118. Constipation is difficult to define because there
is considerable individual variation, but it is usually taken to mean infrequent
passage of stool (< three times per week) or the difficult passage of hard stools.
Steatorrhoea
Steatorrhoea is the passage of pale, bulky stools that contain fat (>17 mmol or
6 g per day) and indicates fat malabsorption as a result of small bowel disease,
68 Gastroenterology and nutrition
pancreatic disease (resulting in lipase deficiency), or cholestatic liver/biliary
disease (resulting in intestinal bile salt deficiency). The stools are offensive,
often float because of increased air content and are difficult to flush away.
Abdominal pain
Table 3.2 lists the common causes of abdominal pain based on the usual site of pain.
Abdominal pain presenting as an acute abdomen is also discussed on page 121.
INVESTIGATION OF GASTROINTESTINAL DISEASE
Baseline routine blood tests, often including coeliac serology, should be performed in patients with gastrointestinal complaints. Additional investigations,
including endoscopy and radiological imaging, may be required depending
on the suspected underlying pathology. Faecal markers of intestinal inflammation and tissue damage, e.g. faecal calprotectin, are able to distinguish
inflammatory bowel disease from non-inflammatory functional disease
(e.g. irritable bowel syndrome) with high diagnostic accuracy.
Table 3.2 Causes of abdominal pain by location
Epigastric Lower abdomen
Peptic ulceration Functional pain
Functional dyspepsia Diverticulitis
Gastric cancer Appendicitis
Pancreatitis Gynaecological: salpingitis, ovarian cyst/
Pancreatic cancer Ectopic pregnancy
Upper abdomen Inflammatory bowel disease
Hepatitis
Hepatic congestion Diffuse or varied site
Pancreatitis
Biliary pain Mesenteric ischaemia
Subdiaphragmatic abscess Bowel obstruction
Functional pain Peritonitis
Splenic abscess or infarct Ruptured aortic aneurysm
Cardiac (myocarditis, ischaemia) Metabolic (DKA, porphyria)
Pneumonia Familial Mediterranean fever
DKA, Diabetic ketoacidosis.
cancer
Renal or urinary tract
Gastroenteritis
Herpes zoster (pain precedes the rash)
Investigation of Gastrointestinal Disease 69
Endoscopy
Video endoscopes relay colour images to a high-definition television monitor.
The tip of the endoscope can be angulated in all directions, and channels
in the instrument are used for air insufflation, water injection, suction,
and for the passage of accessories, such as biopsy forceps or brushes for
obtaining tissue, snares for polypectomy and needles for injection therapies.
Permanent photographic or video records of the procedure are obtained.
Mucosal biopsy is often an integral part of the examination; multiple biopsies
(8–10) are taken in suspected cancer to reduce sampling error and falsenegative results.
Oesophagogastroduodenoscopy (OGD, ‘gastroscopy’)
A flexible endoscope is passed through the mouth into the oesophagus, stomach and duodenum following the administration of local anaesthetic spray to
the pharynx and/or light sedation with intravenous midazolam. Patients fast
for 6 hours prior to the procedure and must not drive for 24 hours after intravenous sedation. OGD is used in the investigation of dyspepsia, dysphagia,
weight loss and iron deficiency anaemia. Duodenal biopsies can be obtained
to establish a diagnosis of coeliac disease, and therapeutic options include
arresting upper gastrointestinal bleeding, dilatation of oesophageal strictures
and stent insertion for palliation of oesophageal malignancy. The mortality for
diagnostic endoscopy is 0.001% with significant complications in 1:10 000,
usually when performed as an emergency (e.g. GI haemorrhage).
Sigmoidoscopy
This is performed with a rigid instrument to examine the rectum and distal
sigmoid, or with a flexible instrument to examine the whole of the left colon.
Bowel preparation is required prior to the procedure and patients are asked
to take one or two phosphate enemas. Sedation is rarely required for this
procedure.
Colonoscopy
This allows visualization of the entire colon and terminal ileum. Bowel cleansing solutions (p. 132) are given in advance of the procedure to clear the
bowel of solid contents. Intravenous analgesia (e.g. fentanyl) and sedation
(e.g. midazolam) may be required. Colonoscopy is useful for the investigation
of patients with altered bowel habit, rectal bleeding or as a screening tool
for colorectal cancer. Cancer, polyps and diverticular disease are the most
common significant findings. In addition to being an investigative procedure, colonoscopies provide therapeutic options, such as removal of polyps
(polypectomy) or diathermy of bleeding lesions, such as angiodysplasia.
Complications of colonoscopy (± polypectomy) are bowel perforation and
bleeding. Additional complications of respiratory depression and hypotension
may occur as a result of the sedation.
70 Gastroenterology and nutrition
Endoscopic retrograde cannulation of biliary and pancreatic duct
(ERCP) combines endoscopy and fluoroscopy to visualize the pancreatico-
biliary tree. Rather than a diagnostic test, it is used for interventions such
as gallstone extraction and stenting benign and malignant strictures in the
common bile duct. Complications include perforation, pancreatitis and sepsis.
Endoscopic ultrasound (EUS) is performed with a gastroscope
incorporating an ultrasound probe at the tip. It is used diagnostically for
lesions in the oesophageal or gastric wall, including the detailed TNM staging
(see Table 3.15) of oesophageal/gastric cancer and for the detection and
biopsy of pancreatic tumours and cysts.
Endoanal and endorectal ultrasonography are performed to define
the anatomy of the anal sphincters to detect perianal disease and stage
superficial rectal tumours.
Balloon enteroscopy allows a specially trained endoscopist to examine
the small bowel from the duodenum to the ileum from either an oral or rectal
approach.
Capsule endoscopy involves the patient swallowing a small wireless
pill-sized camera to allow visualization of the gastrointestinal mucosa. It is
used for the evaluation of obscure GI bleeding (after negative gastroscopy
and colonoscopy) and for the detection of small bowel tumours and occult
inflammatory bowel disease. It should be avoided if strictures are suspected.
Imaging
Plain X-rays of the chest and abdomen are used in the investigation of the
acute abdomen. They may show free gas with a perforated viscus, dilated
loops of bowel with intestinal obstruction and colonic dilatation in a patient
with severe ulcerative colitis (UC). Calcification in the pancreas (just to the
left of L1) indicates chronic pancreatitis, and faecal loading is seen with
constipation.
Ultrasound
Transabdominal ultrasound is useful for visualization of the liver, gall
bladder and biliary tree, and kidneys. This non-invasive test is commonly
used for investigation of abnormal liver blood tests, hepatomegaly and for
characterization of abdominal masses. It is also used for the detection of
bowel wall thickening and determining the extent of involved segments in
Crohn’s disease, although is not disease specific. It is used to guide needle
placement for biopsies of the liver and solid mass lesions and for drainage of
ascites and inflammatory collections.
Computed tomography (CT) scan
CT scanning (p. 823) is frequently used in the investigation of gastrointestinal
disease, particularly in the staging of intra-abdominal malignancy and in the
investigation and assessment of the acute abdomen (demonstrating perfo-
Investigation of Gastrointestinal Disease 71
(Ai)
(Aii)
(Aiii) (B)
rated viscus, inflammation, e.g. appendicitis, the site and cause of intestinal
obstruction and renal calculi). CT colonography/CT pneumocolon (virtual
colonoscopy) provides a computer-simulated intraluminal view of the air-filled
colon. Like conventional colonoscopy it requires full bowel preparation (p. 132)
and air distension of the colon. The images obtained can visualize colonic
polyps (Fig. 3.1) and cancer, but biopsies cannot be taken nor polyps removed.
It is mainly used where conventional colonoscopy cannot be performed
because of patient intolerance or technical difficulties. Unprepared abdominal
and pelvic CT scanning is a good test for colon cancer in the frail or elderly
patient who may not tolerate the necessary bowel preparation for conventional
or CT colonography.
Risks associated with CT scanning include allergy to intravenous contrast
and exposure to radiation. The effective radiation dose from abdominal and
pelvic CT scan or CT colonography is 10 mSv and equivalent to about 3 years’
natural background radiation. Multiple CT scans in an individual may increase
cancer risk as a result of radiation exposure.
Fig. 3.1 Colon polyps seen at (Ai–Aiii) colonoscopy and (B) computed tomography
(CT) colonography. Aii is after endoscopic resection of the polyps in Ai.
72 Gastroenterology and nutrition
Magnetic resonance imaging (MRI)
MRI uses no radiation and is particularly useful in the evaluation of rectal cancers and abscesses and fistulae in the perianal region. It is also useful in small
bowel disease (MR enteroclysis) and in hepatobiliary and pancreatic disease.
Positron emission tomography (PET)
PET scanning relies on detection of the metabolism of fluorodeoxyglucose.
It is used for staging oesophageal, gastric and colorectal cancer and in the
detection of metastatic and recurrent disease.
Contrast studies
Ingestion of barium followed by X-ray imaging allows examination of the
oesophagus (barium swallow), stomach and duodenum (barium meal) and
small intestine (barium follow-through). These techniques are less sensitive than endoscopy, particularly for small mucosal lesions. However, unlike
endoscopy, barium swallow will demonstrate motility problems in the investigation of dysphagia. MRI of the small bowel is being used more frequently
as it does not involve radiation.
Oesophageal physiology testing
Insertion of probes into the lower oesophagus via the nose allows continual
measurement over 24 hours of acid (pH monitoring) and volume (by impedance testing) reflux of gastric contents. Data are captured on a small device
worn on a belt and transferred to a computer at the end of the 24-hour
period. These methods record the frequency and duration of reflux episodes
and correlation with symptoms. They are performed prior to surgical treatment of reflux or in difficult diagnostic cases.
Oesophageal manometry involves the passage of a small tube containing
several pressure transducers into the oesophagus via the nose. Oesophageal
peristalsis and pressure are assessed on swallowing. Manometry is used
in the investigation of suspected oesophageal motility disorders in patients
with dysphagia.
THE MOUTH
Problems in the mouth are common and, although often trivial, they can
cause severe symptoms.
Mouth ulcers
Non-infective
• Recurrent aphthous ulceration is common and affects at least 20% of the
population; in most cases the aetiology is unknown. There are recurrent