Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 19 GASTROINTESTINAL DRUGS
reported to be incompatible in solution: amphotericin
B, ampicillin sodium, chloramphenicol sodium
succinate, dimenhydrinate, hydrocortisone sodium
succinate, penicillin G sodium, phenobarbital
sodium. Chlorothiazide sodium and methicillin are
also incompatible with chlorpromazine. In addition,
do not mix with other drugs or diluents containing
parabens as preservatives.
Metoclopramide
Clinical applications
Metoclopramide is indicated for control of vomiting
associated with:
● various emesis-inducing disorders involving either
stimulation of the CTZ or depressed
gastrointestinal motility
● cancer chemotherapy
● gastroesophageal reflux
● decreased gastric emptying associated with:
– inflammatory gastrointestinal disorders
– gastric ulcers
– gastric neoplasia
– autonomic neuropathy (diabetes mellitus)
– postoperative gastric dilation and volvulus
surgery/intervention
– abnormal gastric motility.
Although metoclopramide is sometimes recommended
for endoscopic procedures to facilitate passage of the
endoscope through the pylorus, this effect was not confirmed
in a well-controlled study of the effect of pharmacological
agents on the ease of endoscopic intubation
in dogs. In fact, increased antral motility caused by
metoclopramide makes endoscopic intubation more
difficult.
Mechanism of action
Centrally, metoclopramide antagonizes D 2 -dopaminergic
receptors and 5-HT 3 serotonergic receptors and has a
peripheral cholinergic effect. The antiemetic properties of
metoclopramide may be related to 5-HT 3 receptor antagonism
rather than D 2 -receptor antagonism, even though
it has been classified for many years as an antidopaminergic
drug. The evidence supporting reassessment of its
mode of action includes the observation that analogs of
metoclopramide have been developed that are effective
antiemetics but show little or no dopamine antagonism.
They are very specific 5-HT 3 antagonists and it is therefore
believed that the serotonin-antagonist effects of
metoclopramide account for a large part of its antiemetic
effects. However, antidopaminergic mechanisms are
still believed to play a role in the antiemetic action of
metoclopramide.
Metoclopramide is commonly believed to cause
increased gastric emptying, primarily through antagonism
of peripheral D 2 -receptors, although enhanced
cholinergic activity may also be involved. However,
there is evidence from some animal studies that the
gastrointestinal effects of metoclopramide may be disassociated
from its dopamine receptor-blocking action.
Intact vagal innervation is not necessary for enhanced
motility but anticholinergic drugs will negate its effects.
Metoclopramide has also been demonstrated to have
anticholinesterase effects and there are suggestions that
this drug sensitizes gastrointestinal smooth muscle to
the effects of acetylcholine.
Gastrointestinal effects include increased tone and
amplitude of gastric contractions, relaxation of the
pyloric sphincter and increased duodenal and jejunal
peristalsis. Gastric emptying and intestinal transit times
can be significantly reduced. There is little or no effect
on colonic motility.
A beneficial effect of metoclopramide could not be
demonstrated in dogs with gastric dilation and volvulus
and delayed gastric emptying treated with metoclopramide
postsurgically. However, as the study involved
use of liquids rather than solids, it might have been difficult
to demonstrate an effect even if gastric motility
was enhanced.
Metoclopramide will also increase lower esophageal
pressure and reduce gastroesophageal reflux. This effect
is abolished by diphenhydramine. The increased lower
esophageal pressure induced by metoclopramide is not
sufficient to prevent gastric reflux in anesthetized dogs,
although it does lower the risk.
Studies have indicated that metoclopramide has a
biphasic effect on ureteral motility, increasing motility
at low doses and inhibiting it at high doses. Semen
volume is reported to be reduced in dogs treated with
metoclopramide but sperm number was not significantly
affected.
Formulations and dose rates
Metoclopramide is available as a veterinary preparation in tablet and
injectable formulations in some countries (e.g. Australia) but only as
a human preparation in others (e.g. USA, UK). Metoclopramide is
photosensitive and should be stored in light-resistant containers at
room temperature.
DOGS AND CATS
• 0.2–0.5 mg/kg IM, SC, PO q.6–8 h
• 1–2 mg/kg IV infusion over 24 h
The effi cacy of metoclopramide is believed to be enhanced by administering
1–2 mg/kg/d by a constant-rate infusion instead of intermittent
boluses.
When used to treat disorders of gastric motility and esophageal
refl ux, metoclopramide should be administered at a dose of 0.2–
0.5 mg/kg PO 30 min before meals.
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