Clinical Pharmacology and Therapeutics

PANCREATIC INSUFFICIENCY 259
Ciprofloxacin is occasionally used for prophylaxis against
travellers’ diarrhoea, but routine use is not recommended
due to consequent encouragement of bacterial resistance.
Lactobacillus preparations have not been shown to be effective.
Early treatment of diarrhoea with ciprofloxacin will control
the great majority of cases and this, together with oral
replacement of salts and water, is the currently preferred
approach.
PSEUDOMEMBRANOUS COLITIS
Broad-spectrum antibacterial drug therapy is sometimes associated
with superinfection of the intestine with toxin-producing
Clostridium difficile. Debilitated and immunosuppressed
patients are at particular risk. The infection can be transmitted
from person to person. Withdrawal of the antibacterial drug
and the introduction of oral metronidazole or vancomycin
should be instituted.
IRRITABLE BOWEL SYNDROME
This motility disorder of the gut affects approximately 10% of
the population. Although the symptoms are mostly colonic,
patients with the syndrome have abnormal motility throughout
the gut and this may be precipitated by dietary items, such
as alcohol or wheat flour. The important management principles
are first to exclude a serious cause for the symptoms
and then to determine whether exclusion of certain foods or
alcohol would be worthwhile. An increase in dietary fibre
over the course of several weeks may also reduce the symptoms.
Psychological factors may be important precipitants
and counselling may be helpful. Drug treatment is symptomatic
and often disappointing.
• Anticholinergic drugs, such as hyoscine, have been
used for many years, although evidence of their
efficacy is lacking. The oral use of better absorbed
anticholinergics, such as atropine, is limited by their side
effects.
• Mebeverine (135 mg before meals three times daily)
directly relaxes intestinal smooth muscle without
anticholinergic effects. Its efficacy is marginal.
• Peppermint oil relaxes intestinal smooth muscle and is
given in an enteric-coated capsule which releases its
contents in the distal small bowel. It is given before meals
three times daily.
• Antidiarrhoeal drugs, such as loperamide, reduce
associated diarrhoea.
• Psychotropic drugs, such as antipsychotics and
antidepressants with anticholinergic properties, have also
been effective in some patients. In general, however, they
should be avoided for such a chronic and benign
condition because of their serious adverse effects (see
Chapters 19 and 20).
PANCREATIC INSUFFICIENCY
It is important to remember that, amongst the many causes of
pancreatitis, certain drugs can very occasionally be an aetiological
factor (Table 34.5).
Exocrine pancreatic insufficiency is an important cause of
steatorrhoea. The pancreas has a large functional reserve and
malabsorption does not usually occur until enzyme output is
reduced to 10% or less of normal. This type of malabsorption
is usually treated by replacement therapy with pancreatic
extracts (usually of porcine origin). Unfortunately, although
useful, these preparations rarely abolish steatorrhoea. A number
of preparations are available, but the enzyme activity
varies between preparations – one with a high lipase activity
is most likely to reduce steatorrhoea. Unfortunately, less
than 10% of the lipase activity and 25% of the tryptic activity
is recoverable from the duodenum regardless of the dose
schedule. This limited effectiveness of oral enzymes is
partly due to acid–peptic inactivation in the stomach and
duodenum. H 2 -antagonists decrease both acidity and volume
of secretion and retard the inactivation of exogenous
pancreatic enzymes. They are given as an adjunct to these
preparations.
Supplements of pancreatin are given to compensate
for reduced or absent exocrine secretion in cystic fibrosis,
pancreatectomy, total gastrectomy and chronic pancreatitis.
Pancreatin is inactivated by gastric acid and therefore preparations
are best taken with or immediately before or after food.
Gastric acid secretion can be reduced by giving an H 2 -blocker
about one hour beforehand, or antacids may be given concurrently
to reduce acidity.
Pancreatin is inactivated by heat and, if mixed with liquids
or food, excessive heat should be avoided. The dose is
adjusted according to size, number and consistency of stools
such that the patient thrives.
Pancreatin can irritate the perioral skin and buccal mucosa
if it is retained in the mouth and excessive doses can cause
perianal irritation. The most frequent side effects are gastrointestinal
ones including nausea, vomiting and abdominal
discomfort. Hyperuricaemia and hyperuricuria have been
associated with very high doses of the drug.
Table 34.5: Drugs that are associated with pancreatitis (this is uncommon)
Asparaginase
Azathioprine
Corticosteroids
Dideoxyinosine (DDI)
Ethanol
Oestrogens
Pentamidine
Sodium valporate
Sulphonamides and
sulfasalazine
Tetracycline
Thiazides