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

1348 options. For patients with gastroparesis, first-line therapy
consists of metoclopramide, which accelerates gastric
emptying and also has anti-emetic effects.
Erythromycin, a motilin agonist, also has been
employed, but is most effective for short-term use. For
patients with small-bowel dysmotility, the choices are
even more limited: Metoclopramide and erythromycin
generally do not work; therapy with octreotide may
benefit a subset of patients.
Constipation. Although many choices exist for this
condition, most therapies are empirical and non-specific.
Constipation often can be addressed by simple measures
such as increasing fiber intake, avoiding constipating
medications, and the judicious use of osmotic
laxatives on an as-needed basis. For more persistent
symptoms, a specific prokinetic 5-HT 4
receptor agonist
or Cl − channel agonist may be effective in some
patients. Stimulant laxatives, although effective, should
be avoided for long-term use. Patients with chronic constipation
who do not respond to simple measures should
undergo further testing to discover uncommon but specific
disorders of colonic or anorectal motility.
Diarrhea. In most cases, an attempt should be made to
find the underlying cause and to target it specifically. If
no such cause is found, chronic diarrhea can be treated
empirically, with the simplest approach being bulkforming
and hygroscopic agents, followed by opioids
such as loperamide for diarrhea associated with inflammatory
bowel disease or diphenoxylate/difenoxin can
be used to manage acute exacerbations of chronic functional
diarrhea.
SECTION VI
DRUGS AFFECTING GASTROINTESTINAL FUNCTION
Irritable Bowel Syndrome. IBS consists of abdominal pain
and discomfort associated with diarrhea, constipation, or
alternating bouts of diarrhea and constipation. This common
syndrome requires a combination of pharmacological
and behavioral approaches that include dietary
modifications and psychological counseling. No one therapy
will work for all patients and currently there are no
therapies focused on IBS that treat both the pain and GI
symptoms. Anti-spasmodics are useful by themselves in
mild cases and as adjuncts in a regimen that includes tricyclic
anti-depressants for more persistent pain.
Nausea and Vomiting. The development of the 5-HT 3
receptor antagonists has led to a major advances in the
treatment of nausea and vomiting, especially in the
post-chemotherapy and post-operative settings.
Anticholinergics are most effective in motion sickness.
Antihistamines and related drugs still are useful for
empirical treatment of nausea from a variety of causes.
Dronabinol or nabilone may be an effective agent for
some refractory cases. The clinical utility of newer
agents such as aprepitant in situations other than postchemotherapy
nausea will be tested in coming years.
BIBLIOGRAPHY
Borowitz D, Baker RD, Stallings V. Consensus report on nutrition
for pediatric patients with cystic fibrosis. J Pediatr
Gastroenterol Nutr, 2002, 35:246–259.
De Giorgio R, Barbara G, Furness JB, Tonini M. Novel therapeutic
targets for enteric nervous system disorders. Trends
Pharmacol Sci, 2007, 28:473–481.
Eutamene H, Bradesi S, Larauche M, et al. Guanylate cyclase
C-mediated antinociceptive effects of linaclotide in rodent
models of visceral pain. Neurogastroenterol Motil, 2009
August 25 (Epub ahead of print).
Furness JB. The Enteric Nervous System. Wiley-Blackwell,
Oxford, 2006, pp 286.
Gale JD. The use of novel promotility and prosecretory agents
for the treatment of chronic idiopathic constipation and irritable
bowel syndrome with constipation. Adv Ther, 2009,
26:519–530.
Gershon MD, Tack J. The serotonin signalling system: From
basic understanding to drug development for functional GI disorders.
Gastroenterology, 2007, 132:397–414.
Grunberg SM, Hesketh PJ. Control of chemotherapy-induced
emesis. N Engl J Med, 1993, 329:1790–1796.
Grundy D, Al-Chaer ED, Aziz Q, et al. Fundamentals of neurogastroenterology:
Basic science. Gastroenterology, 2006,
130:1391–1411.
Hornby PJ. Central neurocircuitry associated with emesis. Am J
Med, 2001, 111(suppl 8A):106S–112S.
Holzer P. Opioid receptors in the gastrointestinal tract. Reg
Peptides, 2009, 155:11–17.
Izzo AA, Gaginella TS, Mascolo N, Capasso F. Recent findings
on the mode of action of laxatives: The role of platelet activating
factor and nitric oxide. Trends Pharmacol Sci, 1998,
19:403–405.
Joyce J. Ulysses (1922). The Gabler edition, Random House, NY,
1986, p. 56.
Kreek MJ. Constipation syndromes. In: A Pharmacological
Approach to Gastrointestinal Disorders. (Lewis JH, ed.),
Williams & Wilkins, Baltimore, 1994, pp. 179–208.
Kunze WA, Furness JB. The enteric nervous system and regulation
of intestinal motility. Annu Rev Physiol, 1999, 61:
117–142.
Mertz HR. Drug therapy: Irritable bowel syndrome. N Engl J
Med, 2003, 349:2136–2146.
Moitinho E, Planas R, Banares R, et al. Multicenter randomized
controlled trial comparing different schedules of somatostatin
in the treatment of acute variceal bleeding. J Hepatol, 2001,
35:712–718.
Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical
implications of the brain-gut-enteric microbiota axis. Nat Rev
Gastroenterol Hepatol, 2009, 6:306–314.
Sanger GJ. Motilin, ghrelin and related neuropeptides as targets
for the treatment of GI diseases. Drug Disc Today, 2008,
13:234–239.