Cisapride.* Cisapride acts by stimulating serotonin
type 4 receptors in the myenteric plexus. It has
proved effective in the treatment of idiopathic gas-
troparesis, but has no antiemetic property.26 It is
also effective in the treatment of gastroesophageal
reflux disease,27 which can be aggravated by gastro-
paresis. Major side effects include abdominal
cramping, diarrhea, and headache. The coadminis-
tration of azole antifungal drugs, macrolides (includ-
ing erythromycin and clarithromycin), HIV protease
inhibitors and some antidepressants is contraindicat-
ed for fear of increasing serum level of cisapride
resulting in prolonged QT interval and torsade de
pointes. However, its limited side effects and overall
efficacy27 make it an attractive option for the long-
term treatment of gastroparesis. Standard dosage is
10 to 20 mg two to four times a day orally, 30 min-
utes before meals and at bedtime. If no effect is
seen with the tablet, the suspension should be used.
Metoclopramide. Metoclopramide is a dopamine
antagonist with a prokinetic and antiemetic proper-
ties. Major side effects such as tremors and Parkin-
son-like syndrome result from its antidopaminergic
activity in the central nervous system, and limit its
long-term use.28 It is particularly useful when given
intravenously (or subcutaneously in outpatient set-
ting), for acute exacerbation of nausea and vomit-
ing, with doses ranging from 5 to 20 mg, repeated
up to four times. For chronic use, oral administra-
tion of the tablet or elixir is available at doses of 10
to 20 mg, 30 minutes before meals and at bedtime.
Domperidone. Like metoclopramide, domperidone
is a dopamine receptor antagonist, with minimal
penetration of the blood-brain barrier that accounts
for absence of extrapyramidal side effects.29 It also
has prokinetic and antiemetic properties. Its fewer
central nervous system side effects, greater efficacy,
and better tolerance make it an attractive alterna-
tive to metoclopramide.29 Standard dosage is 10 to
30 mg orally 30 before meals and at bedtime. It is
available worldwide, and is expected to be
approved in the US in the near future.
ry setting (ranging from 1 to 19 months) was shown
effective but associated with high frequency of line
sepsis.32 Currently, erythromycin is most useful in
the short-term treatment of patients with gastro-
paresis, or in combination with other prokinetic
agents, with the exception of cisapride.
Recommended doses are 125 to 250 mg orally, up
to 4 times a day, 30 minutes before meals and at
bedtime (tablets or suspension form) or 100 to 250
mg intravenous bolus over 20 to 60 minutes.
Combination therapy. Treatment with more than a
single prokinetic may be necessary when
monotherapy fails. When combination therapy is
indicated, it is recommended that drugs with differ-
ent mechanisms of action be considered. The addi-
tion of metoclopramide to cisapride is particularly
effective,33 though metoclopramide and ery-
thromycin can also be used. When available, the
combination of cisapride and domperidone may be
particularly desirable.
Refractory patients. A limited number of options
are available for patients who fail to respond to
medical therapy, and particularly for those who sus-
tain weight loss. The insertion of a feeding jejunos-
tomy tube (endoscopic, laparoscopic, or open
surgery) was shown to improve symptoms,34 glu-
cose control, and gastric emptying.35 A gastrostomy
is rarely indicated. Gastric surgery, such as subtotal
gastrectomy, which may be effective in other types
of gastroparesis, has not been successful in patients
with diabetes.36 More recently, a novel technique of
pacing the stomach using electrodes attached to the
surface of the stomach has been reported to
improve gastric motility and symptoms in a few
patients with refractory diabetic gastropathy.37 The
clinical role of this interesting approach requires
further study. CT
R E F E R E N C E S
1. National Diabetes Data Group. Diabetes in America: Diabetes
Data Compiled 1984. Bethesda, MD: National Institutes of
Health, 1985. (NIH publication no. 85–1468.)
2. Bloomgarden ZT. American Diabetes Association Annual
Meeting 1998: Epidemiology and neuropathy. Diabetes Care.
1998;21:2023–2027.
3. Yahihashi S, Sima AAF. Diabetic autonomic neuropathy in
the BB rat. Ultrastructural and morphometric changes in
sympathetic nerves. Diabetes. 1985;34:558–564.
4. Yagihashi S, Sima AAF. Diabetic autonomic neuropathy in
BB rat. Ultrastructural and morphometric changes in sym-
pathetic nerves. Diabetes. 1986;35:733–743.
5. Monckton G, Pehowitch E. Autonomic neuropathy in the
streptozotocin diabetic rat. Can J Neurol Sci. 1980;7:135–
141.
6. Lincoln J, Bokor JT, Crowe R, Griffith SG, Haven AJ, Burn-
stock G. Myenteric plexus in streptozotocin-treated rats.
Neurochemical and histochemical evidence for diabetic neu-
Erythromycin. Macrolide antibiotics and their
nonantibacterial analogues enhance gastric and
small bowel motor function by binding to motilin
receptors in the gut.30 Erythromycin, given intra-
venously, is a potent stimulant for gastric emptying
in diabetic patients with gastroparesis. This effect is
markedly diminished when given orally.30 In addi-
tion, the overall therapeutic effect is also dimin-
ished over time when the drug is given orally.31
Long-term intravenous administration in ambulato-
*Since the submission of this manuscript, cisapride was removed from the US
market because of cardiac arrhythmias.
58
COMP THER. 2001;27(1)