A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition
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256 ALIMENTARY SYSTEM AND LIVER<br />
IMMUNOSUPPRESSIVE DRUGS<br />
Although the exact pathogenetic mechanisms involved in<br />
inflammatory bowel disease remain unclear, there is abundant<br />
evidence that the immune system (both cellular <strong>and</strong> humoral)<br />
is activated in the intestine <strong>of</strong> patients with inflammatory<br />
bowel disease. This forms the rationale for the use <strong>of</strong> immunosuppressive<br />
agents in the group <strong>of</strong> patients who do not<br />
respond to therapy with aminosalicylates or glucocorticosteroids.<br />
General indications for their use include patients who<br />
have been on steroids for more than six months despite efforts<br />
to taper them <strong>of</strong>f, those who have frequent relapses, those with<br />
chronic continuous disease activity <strong>and</strong> those with Crohn’s<br />
disease with recurrent fistulas. Patients with ulcerative colitis<br />
may benefit from a short course <strong>of</strong> ciclosporin (unlicensed<br />
indication). Patients with unresponsive or chronically active<br />
inflammatory bowel disease may benefit from azathioprine or<br />
mercaptopurine, or (in the case <strong>of</strong> Crohn’s disease) onceweekly<br />
methotrexate (these are all unlicensed indications).<br />
Infliximab, a monoclonal antibody that inhibits tumour<br />
nerosis factor (see Chapters 16 <strong>and</strong> 26) is licensed for the<br />
management <strong>of</strong> severe active Crohn’s disease <strong>and</strong> moderate to<br />
severe ulcerative colitis in patients whose condition has not<br />
responded adequately to treatment with a glucocorticosteroid<br />
<strong>and</strong> a conventional immunosuppressant or who are intolerant<br />
<strong>of</strong> them. Infliximab is also licensed for the management <strong>of</strong><br />
refractory fistulating Crohn’s disease. Maintenance therapy<br />
with infliximab should be considered for patients who<br />
respond to the initial induction course.<br />
OTHER THERAPIES<br />
Metronidazole may be beneficial for the treatment <strong>of</strong> active<br />
Crohn’s disease with perianal involvement, possibly through<br />
its antibacterial activity. It is usually given for a month, but no<br />
longer than three months because <strong>of</strong> concerns about developing<br />
peripheral neuropathy. Other antibacterials should be<br />
given if specifically indicated (e.g. sepsis associated with fistulas<br />
<strong>and</strong> perianal disease) <strong>and</strong> for managing bacterial overgrowth<br />
in the small bowel.<br />
Antimotility drugs such as codeine <strong>and</strong> loperamide (see<br />
below) <strong>and</strong> antispasmodic drugs may precipitate paralytic<br />
ileus <strong>and</strong> megacolon in active ulcerative colitis; treatment <strong>of</strong><br />
the inflammation is more logical. Laxatives may be required in<br />
proctitis. Diarrhoea resulting from the loss <strong>of</strong> bile-salt absorption<br />
(e.g. in terminal ileal disease or bowel resection) may<br />
improve with colestyramine, which binds bile salts.<br />
Key points<br />
Inflammatory bowel disease<br />
The cause is unknown.<br />
There is local <strong>and</strong> sometimes systemic inflammation.<br />
• Correct dehydration, nutritional <strong>and</strong> electrolyte imbalance.<br />
• Drug therapy: aminosalicylates; glucocorticosteroids;<br />
other immunosuppressive agents.<br />
CONSTIPATION<br />
When constipation occurs, it is important first to exclude both<br />
local <strong>and</strong> systemic disease which may be responsible for the<br />
symptoms. Also, it is important to remember that many drugs<br />
can cause constipation (Table 34.4).<br />
In general, patients with constipation present in two ways:<br />
1. Long-st<strong>and</strong>ing constipation in otherwise healthy people<br />
may be due to decreased colon motility or to dyschezia, or<br />
to a combination <strong>of</strong> both. It is usually sufficient to reassure<br />
the patient <strong>and</strong> to instruct them in the importance <strong>of</strong> reestablishing<br />
a regular bowel habit. This should be<br />
combined with an increased fluid intake <strong>and</strong> increased<br />
bulk in the diet. Bran is cheap <strong>and</strong> <strong>of</strong>ten satisfactory. As an<br />
alternative, non-absorbed bulk substances such as<br />
methylcellulose, ispaghula or sterculia are helpful. The<br />
other laxatives described below should only be tried if<br />
these more ‘natural’ treatments fail.<br />
2. Loaded colon or faecal impaction – sometimes it is<br />
necessary to evacuate the bowel before it is possible to<br />
start re-education, particularly in the elderly or those who<br />
are ill. In these cases, a laxative such as senna combined<br />
with glycerol suppositories is appropriate.<br />
Table 34.4: Drugs that can cause constipation<br />
Aluminium hydroxide<br />
Amiodarone<br />
Anticholinergics (older antihistamines)<br />
Diltiazem<br />
Disopyramide<br />
Diuretics<br />
Iron preparations<br />
Opioids<br />
Tricyclic antidepressants<br />
Verapamil<br />
LAXATIVES<br />
Laxatives are still widely although <strong>of</strong>ten inappropriately used<br />
by the public <strong>and</strong> in hospital. There is now a greater knowledge<br />
<strong>of</strong> intestinal pathophysiology, <strong>and</strong> <strong>of</strong> outst<strong>and</strong>ing importance<br />
is the finding that the fibre content <strong>of</strong> the diet has a<br />
marked regulatory action on gut transit time <strong>and</strong> motility <strong>and</strong><br />
on defecation performance.<br />
As a general rule, laxatives should be avoided. They are<br />
employed:<br />
• if straining at stool will cause damage (e.g. postoperatively,<br />
in patients with haemorrhoids or after<br />
myocardial infarction);