DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1360 for the treatment of Crohn’s disease should have their doses reduced
before starting natalizumab treatment.
The role of anti- TNF therapies for steroid- refractory or
steroid- dependent ulcerative colitis is less clear. The rationale for
their use is based on finding elevated levels of TNFα in the mucosa
of patients. Large controlled clinical trials have demonstrated that
anti- TNF agents significantly reduce the severity of the inflammation.
The rates of clinical remission range from 26-34%, with endoscopic
healing in about half the treated patients. Unlike Crohn’s
disease, ulcerative colitis is cured with surgery; thus the cost and
serious adverse events associated with anti- TNF therapy need to be
balanced with the effectiveness of the drug at preventing the need
for colectomy. Currently, it is not known how effective anti- TNF
therapies are for prevention, as opposed to delay, of colectomy.
SECTION VI
DRUGS AFFECTING GASTROINTESTINAL FUNCTION
ANTIBIOTICS AND PROBIOTICS
An emerging concept is that a balance in the GI tract normally
exists among the mucosal epithelium, the normal
gut flora, and the immune response (Preidis &
Versalovic, 2009). Moreover, there are experimental and
clinical data that colonic bacteria may either initiate or
perpetuate the inflammation of IBD (Salzmann and
Bevins, 2008), and, as mentioned earlier (“Pathogenesis
of Inflammatory Bowel Disease”), recent studies have
implicated specific bacterial antigens in the pathogenesis
of Crohn’s disease. Thus, certain bacterial strains may
be either pro- (e.g., Bacteroides) or anti- inflammatory
(e.g., Lactobacillus), prompting attempts to manipulate
the colonic flora in patients with IBD. Traditionally,
antibiotics have been used to this end, most prominently
in Crohn’s disease. More recently, probiotics have been
used to treat specific clinical situations in IBD.
Antibiotics can be used as:
• adjunctive treatment along with other medications
for active IBD
• treatment for a specific complication of Crohn’s disease
• prophylaxis for recurrence in postoperative Crohn’s
disease
Metronidazole (Sutherland et al., 1991), ciprofloxacin (Arnold
et al., 2002), and clarithromycin are the antibiotics used most frequently.
They are more beneficial in Crohn’s disease involving the
colon than in disease restricted to the ileum. Specific Crohn’s disease-related
complications that may benefit from antibiotic therapy
include intra- abdominal abscess and inflammatory masses, perianal
disease (including fistulas and perirectal abscesses), small- bowel bacterial
overgrowth secondary to partial small- bowel obstruction, secondary
infections with organisms such as C. difficile, and post-operative
complications. Metronidazole may be particularly effective for the
treatment of perianal disease. Post-operatively, metronidazole and
related compounds have been shown to delay the recurrence of Crohn’s
disease. In one study, a 3-month course of metronidazole (20 mg/kg
per day) prolonged the time to both endoscopic and clinical recurrence
(Rutgeerts et al., 1995). The significant side effects of prolonged systemic
antibiotic use must be balanced against their potential benefits,
and definitive data to support their routine use are lacking.
Probiotics are mixtures of putatively beneficial
lyophilized bacteria given orally. Several studies have
provided evidence for beneficial effects of probiotics in
ulcerative colitis and pouchitis (Hedin et al., 2007).
However, the studies have involved relatively small
numbers of patients and the various studies had different
end points. Thus, the utility of probiotics as a primary
therapy for IBD remains unclear.
SUPPORTIVE THERAPY IN
INFLAMMATORY BOWEL DISEASE
Analgesic, anticholinergic, and antidiarrheal agents
play supportive roles in reducing symptoms and
improving quality of life. These drugs should be individualized
based on a patient’s symptoms and are supplementary
to anti- inflammatory medications. Oral
iron, folate, and vitamin B 12
should be administered as
indicated. Loperamide or diphenoxylate (Chapter 46)
can be used to reduce the frequency of bowel movements
and relieve rectal urgency in patients with mild
disease; these agents are contraindicated in patients
with severe disease because they may predispose to the
development of toxic megacolon. Cholestyramine can
be used to prevent bile salt–induced colonic secretion in
patients who have undergone limited ileocolic resections.
Anticholinergic agents (dicyclomine hydrochloride,
etc.; Chapter 9) are used to reduce abdominal
cramps, pain, and rectal urgency. As with the antidiarrheal
agents, they are contraindicated in severe disease
or when obstruction is suspected. Care should be
taken to differentiate exacerbation of IBD from symptoms
that may be related to coexistent functional bowel
disease (Chapter 46).
THERAPY OF INFLAMMATORY BOWEL
DISEASE DURING PREGNANCY
IBD is a chronic disease that affects women in their reproductive
years; thus, the issue of pregnancy often has a significant
impact on medical management. The effects of
IBD on pregnancy and the effects of pregnancy on IBD
are beyond the scope of this chapter. In general, decreased
disease activity increases fertility and improves pregnancy
outcomes. At the same time, limiting medication during
pregnancy is always desired but sometimes conflicts with
the goal of controlling the disease.