Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

ANTIULCER DRUGS
antitussive effects and local anesthetic effects. The anticholinergic
action may in fact be the main mechanism
by which it is effective in motion sickness, as there are
muscarinic receptors in the vestibular system.
Formulations and dose rates
DOGS AND CATS
Diphenhydramine
• 2–4 mg/kg PO, IM q.8-12 h
Dimenhydrinate
• 4–8 mg/kg PO, IM q.8 h
Pharmacokinetics
The pharmacokinetics of these drugs have not been
studied in domestic species. In humans diphenhydramine
is well absorbed after oral administration but
systemic bioavailability is only 40–60% because of firstpass
metabolism. Diphenhydramine and dimenhydrinate
are metabolized in the liver and largely excreted as
metabolites in urine.
Adverse effects
● CNS depression (e.g. lethargy, somnolence,
paradoxical excitement – cats). The sedative effects
may diminish with time.
● Anticholinergic effects (e.g. dry mouth, urinary
retention).
● Gastrointestinal side effects (e.g. vomiting and
diarrhea) are uncommon, but have been reported.
● These drugs should be used with caution if pyloric
or proximal intestinal obstruction is suspected.
● Use with caution in patients with hyperthyroidism,
seizure disorders, cardiovascular disease,
hypertension and closed-angle glaucoma; signs of
ototoxicity may also be masked by these drugs.
Known drug interactions
Increased sedation can occur if antihistamines are combined
with other CNS-depressant drugs. Antihistamines
may counteract the anticoagulatory effects of heparin
or warfarin. Diphenhydramine may exacerbate the
effects of adrenaline (epinephrine).
ANTIULCER DRUGS
Clinical applications
Antiulcer drugs are useful in the specific management of
gastrointestinal ulceration and reflux esophagitis. They
are not usually needed for treatment of simple acute
gastritis.
Relevant pathophysiology
The protective barrier that prevents gastric mucosa from
being damaged by gastric acid includes the following
factors.
● Mucus, with bicarbonate incorporated into the
mucosal gel layer.
● High epithelial turnover (thus a high metabolic rate
and oxygen requirement).
● Tight junctions and lipoprotein layer of epithelial
cells.
● A rich vascular supply.
● Prostaglandins – PGE series and PGI 2 are
protective:
– inhibit gastric acid secretion
– maintain mucosal blood flow
– involved in secretion and composition of healthy
mucus
– may be intercellular messengers for stimulus of
mucosal cell turnover and migration.
Gastrointestinal ulceration may be associated with a
number of events.
● Drugs (aspirin, phenylbutazone, corticosteroids)
● Uremia (toxins, increased gastrin)
● Liver disease (cause not known)
● Stress
● Increased production of HCl (mast cell tumor at
any site, gastrin-producing tumor of the pancreas
(Zollinger–Ellison syndrome))
● Hypotension, e.g. during surgery,
hypoadrenocorticism
● Spinal cord disease
Interruption of the gastric mucosal barrier allows backdiffusion
of gastric acid into the submucosa, which
causes mast cell degranulation, resulting in histamine
release and subsequent further stimulation of acid
production by gastric parietal cells, which enhances
inflammation and edema in the submucosa. The aim of
antiulcer therapy is to repair the mucosal barrier directly,
reduce the amount of gastric acid produced or neutralize
its effect and hence stop the vicious cycle of gut
damage.
A number of classes of antiulcer drugs are available
and numerous agents are available within each class.
There are differences in mechanism of action amongst
groups and in potency amongst individual agents.
However, there is little information as to whether the
reported differences in potency relate to real differences
in clinical efficacy. An example is a recent study in
healthy laboratory dogs, which examined changes in
luminal pH after administration of four acid-blocking
drugs: ranitidine, famotidine, omeprazole and pantoprazole.
Famotidine, pantoprazole and omeprazole significantly
suppressed gastric acid secretion, compared
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