A Textbook of Clinical Pharmacology and Therapeutics

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 immuno-
suppressive agents in the group of patients who do not
respond to therapy with aminosalicylates or glucocorticos-
teroids. 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 azathioprineor
mercaptopurine, or (in the case of Crohn’s disease) once-
weeklymethotrexate(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. Infliximabis 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

Metronidazolemay 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 develop-
ing peripheral neuropathy. Other antibacterials should be
given if specifically indicated (e.g. sepsis associated with fis-
tulas and perianal disease) and for managing bacterial over-
growth in the small bowel.
Antimotility drugs such as codeineandloperamide(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 absorp-
tion (e.g. in terminal ileal disease or bowel resection) may
improve with colestyramine, which binds bile salts.

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 re-
   establishing 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,ispaghulaorsterculiaare 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 sennacombined
   withglycerol suppositoriesis appropriate.

256 ALIMENTARY SYSTEM ANDLIVER

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.

LAXATIVES

Laxatives are still widely although often inappropriately used

by the public and in hospital. There is now a greater know-

ledge of intestinal pathophysiology, and of outstanding import-

ance 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. post-
  operatively, in patients with haemorrhoids or after
  myocardial infarction);

Table 34.4:Drugs that can cause constipation

Aluminium hydroxide

Amiodarone

Anticholinergics (older antihistamines)

Diltiazem

Disopyramide

Diuretics

Iron preparations

Opioids

Tricyclic antidepressants

Verapamil