Clinical Pharmacology and Therapeutics

256 ALIMENTARY SYSTEM AND LIVER
IMMUNOSUPPRESSIVE DRUGS
Although the exact pathogenetic mechanisms involved in
inflammatory bowel disease remain unclear, there is abundant
evidence that the immune system (both cellular and humoral)
is activated in the intestine of patients with inflammatory
bowel disease. This forms the rationale for the use of immunosuppressive
agents in the group of patients who do not
respond to therapy with aminosalicylates or glucocorticosteroids.
General indications for their use include patients who
have been on steroids for more than six months despite efforts
to taper them off, those who have frequent relapses, those with
chronic continuous disease activity and those with Crohn’s
disease with recurrent fistulas. Patients with ulcerative colitis
may benefit from a short course of ciclosporin (unlicensed
indication). Patients with unresponsive or chronically active
inflammatory bowel disease may benefit from azathioprine or
mercaptopurine, or (in the case of Crohn’s disease) onceweekly
methotrexate (these are all unlicensed indications).
Infliximab, a monoclonal antibody that inhibits tumour
nerosis factor (see Chapters 16 and 26) is licensed for the
management of severe active Crohn’s disease and moderate to
severe ulcerative colitis in patients whose condition has not
responded adequately to treatment with a glucocorticosteroid
and a conventional immunosuppressant or who are intolerant
of them. Infliximab is also licensed for the management of
refractory fistulating Crohn’s disease. Maintenance therapy
with infliximab should be considered for patients who
respond to the initial induction course.
OTHER THERAPIES
Metronidazole may be beneficial for the treatment of active
Crohn’s disease with perianal involvement, possibly through
its antibacterial activity. It is usually given for a month, but no
longer than three months because of concerns about developing
peripheral neuropathy. Other antibacterials should be
given if specifically indicated (e.g. sepsis associated with fistulas
and perianal disease) and for managing bacterial overgrowth
in the small bowel.
Antimotility drugs such as codeine and loperamide (see
below) and antispasmodic drugs may precipitate paralytic
ileus and megacolon in active ulcerative colitis; treatment of
the inflammation is more logical. Laxatives may be required in
proctitis. Diarrhoea resulting from the loss of bile-salt absorption
(e.g. in terminal ileal disease or bowel resection) may
improve with colestyramine, which binds bile salts.
Key points
Inflammatory bowel disease
The cause is unknown.
There is local and sometimes systemic inflammation.
• Correct dehydration, nutritional and electrolyte imbalance.
• Drug therapy: aminosalicylates; glucocorticosteroids;
other immunosuppressive agents.
CONSTIPATION
When constipation occurs, it is important first to exclude both
local and systemic disease which may be responsible for the
symptoms. Also, it is important to remember that many drugs
can cause constipation (Table 34.4).
In general, patients with constipation present in two ways:
1. Long-standing constipation in otherwise healthy people
may be due to decreased colon motility or to dyschezia, or
to a combination of both. It is usually sufficient to reassure
the patient and to instruct them in the importance of reestablishing
a regular bowel habit. This should be
combined with an increased fluid intake and increased
bulk in the diet. Bran is cheap and often satisfactory. As an
alternative, non-absorbed bulk substances such as
methylcellulose, ispaghula or sterculia are helpful. The
other laxatives described below should only be tried if
these more ‘natural’ treatments fail.
2. Loaded colon or faecal impaction – sometimes it is
necessary to evacuate the bowel before it is possible to
start re-education, particularly in the elderly or those who
are ill. In these cases, a laxative such as senna combined
with glycerol suppositories is appropriate.
Table 34.4: Drugs that can cause constipation
Aluminium hydroxide
Amiodarone
Anticholinergics (older antihistamines)
Diltiazem
Disopyramide
Diuretics
Iron preparations
Opioids
Tricyclic antidepressants
Verapamil
LAXATIVES
Laxatives are still widely although often inappropriately used
by the public and in hospital. There is now a greater knowledge
of intestinal pathophysiology, and of outstanding importance
is the finding that the fibre content of the diet has a
marked regulatory action on gut transit time and motility and
on defecation performance.
As a general rule, laxatives should be avoided. They are
employed:
• if straining at stool will cause damage (e.g. postoperatively,
in patients with haemorrhoids or after
myocardial infarction);