Clinical Pharmacology and Therapeutics

258 ALIMENTARY SYSTEM AND LIVER
After prolonged use of stimulant laxatives, the colon
becomes dilated and atonic with diminished activity. The cause
is not clear, but this effect is perhaps due to damage to the
intrinsic nerve plexus of the colon. The disorder of bowel motility
may improve after withdrawing the laxative and using a
high-residue diet.
Some people, mainly women, take purgatives secretly. This
probably bears some relationship to disorders such as anorexia
nervosa that are concerned with weight loss, and is also associated
with self-induced vomiting and with diuretic abuse. The
clinical and biochemical features can closely mimic Bartter’s
syndrome and this possibility should always be investigated in
patients in whom the diagnosis of this rare disorder is entertained,
especially adults in whom true Bartter’s syndrome
almost never arises de novo. Features include:
• sodium depletion – hypotension, cramps, secondary
hyperaldosteronism;
• potassium depletion – weakness, polyuria and nocturia
and renal damage.
In addition, there may be features suggestive of enteropathy
and osteomalacia.
Diagnosis and treatment are difficult; melanosis coli may
provide a diagnostic clue. Urinary electrolyte determinations
may help, but can be confounded if the patient is also surreptitiously
taking diuretics.
Case history
A 70-year-old woman who was previously very active but
whose mobility has recently been limited by osteoarthritis
of the knees and hips sees her general practitioner because
of a recent change in bowel habit from once daily to once
every three days. Her current medication includes regular
co-codamol for her osteoarthritis, oxybutynin for urinary
frequency, aluminium hydroxide prn for dyspepsia, and
bendroflumethiazide and verapamil for hypertension.
Following bowel evacuation with a phosphate enema,
proctoscopy and colonoscopy are reported as normal.
Question
Which of this patient’s medications may have contributed
to her constipation?
Answer
• Co-codamol, which contains an opioid–codeine
phosphate.
• Aluminium hydroxide.
• Bendroflumethiazide.
• Verapamil.
• Oxybutynin (an anticholinergic).
preparations (such as Dioralyte ® or Electrolade ® ), which contain
electrolytes and glucose. Antibiotic treatment is indicated
for patients with systemic illness and evidence of bacterial
infection.
Adjunctive symptomatic treatment is sometimes indicated.
Two main types of drug may be employed, that either
decrease intestinal transit time or increase the bulk and viscosity
of the gut contents.
DRUGS THAT DECREASE INTESTINAL TRANSIT TIME
OPIOIDS
For more information on opioid use, see Chapter 25.
Codeine is widely used for this purpose in doses of
15–60 mg. Morphine is also given, usually as a kaolin and
morphine mixture. Diphenoxylate is related to pethidine and
also has structural similarities to anticholinergic drugs. It may
cause drug dependence and euphoria and is usually prescribed
as ‘Lomotil’ (diphenoxylate plus atropine). Overdose
with this drug in children causes features of both opioid and
atropine intoxication and may be fatal.
LOPERAMIDE
Loperamide is an effective, well-tolerated antidiarrhoeal
agent. It antagonizes peristalsis, possibly by antagonizing
acetylcholine release in the intramural nerve plexus of the gut,
although non-cholinergic effects may also be involved. It is
poorly absorbed and probably acts directly on the bowel. The
dose is 4 mg initially, followed by 2 mg after each loose stool
up to a total dose of 16 mg/day. Adverse effects are unusual,
but include dry mouth, dizziness, skin rashes and gastric disturbances.
Excessive use (especially in children) is to be
strongly discouraged.
DRUGS THAT INCREASE BULK AND VISCOSITY
OF GUT CONTENTS
Adsorbents, such as kaolin, are not recommended for diarrhoea.
Bulk-forming drugs, such as ispaghula, methylcellulose
and sterculia are useful in controlling faecal consistency
in ileostomy and colostomy, and in controlling diarrhoea associated
with diverticular disease.
TRAVELLERS’ DIARRHOEA
DIARRHOEA
The most important aspect of the treatment of acute diarrhoea
is the maintenance of fluid and electrolyte balance, particularly
in children and in the elderly. In non-pathogenic diarrhoea or
viral gastroenteritis, antibiotics and antidiarrhoeal drugs are
best avoided. Initial therapy should be with oral rehydration
This is a syndrome of acute watery diarrhoea lasting for one to
three days and associated with vomiting, abdominal cramps
and other non-specific symptoms, resulting from infection
by one of a number of enteropathogens, the most common
being enterotoxigenic Escherichia coli. It probably reflects colonization
of the bowel by ‘unfamiliar’ organisms. Because of the
variable nature of the pathogen, there is no specific treatment.