Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CLASSES OF ANTIULCER DRUGS
Famotidine
Famotidine is not completely absorbed after oral administration
but hepatic first-pass metabolism is minimal.
In humans, the oral bioavailability is approximately
40–50%.
Nizatidine
In dogs, oral absorption is rapid and almost complete
and there is minimal hepatic first-pass metabolism.
Although food improves oral bioavailability, the difference
is not thought to be clinically relevant. Nizatidine
is metabolized in the liver to a number of metabolites
and at least one of these may have activity.
Adverse effects
● In animals, adverse effects appear rare at the doses
commonly used.
● In humans, side effects of cimetidine such as gynecomastia
and antiandrogenic activity and CNS signs
(mental confusion, lethargy and seizures) have been
reported.
● Occasionally, agranulocytosis may occur.
● Transient cardiac arrhythmias may occur if cimetidine,
ranitidine or famotidine are given
intravenously.
● Long-term used of H 2 -antagonists could cause hypoacidity
and bacterial overgrowth in the stomach but
there is no clinical evidence that this is a serious
concern. There is no evidence that rebound hypersecretion
occurs after stopping therapy with cimetidine
or ranitidine.
● Cimetidine has been reported to cause a cutaneous
drug eruption in a cat.
● The dose of the H 2 -antagonists should be reduced by
50% in patients with impaired renal function.
Known drug interactions
● Cimetidine can decrease hepatic microsomal enzyme
systems and thus theoretically can decrease hepatic
metabolism of various drugs, including benzodiazepines,
barbiturates, propranolol, calcium channel
blockers, metronidazole, phenytoin, quinidine, theophylline
and warfarin. This has been demonstrated
in the dog in a study of the pharmacokinetics of
verapamil when cimetidine was administered concurrently.
The clinical significance of this effect has
not been established, although there are anecdotal
reports of cimetidine therapy adversely affecting
dogs receiving phenobarbital. Ranitidine inhibits microsomal
enzyme systems to a much lesser (5–10-fold)
degree.
● Cimetidine and ranitidine may decrease the renal
excretion of procainamide.
● Famotidine may exacerbate leukopenias if given
concurrently with other bone marrow-suppressing
agents.
● Nizatidine may increase salicylate levels in patients
taking high doses of aspirin.
● Anticholinergic agents (e.g. atropine and propantheline)
may negate the prokinetic effects of ranitidine
and nizatidine.
● The increased intragastric pH associated with H 2 -
antagonist administration may reduce the absorption
of drugs that require an acid medium for dissolution
and absorption, such as ketoconazole.
● It is recommended that at least 2 h elapses between
dosing with cimetidine and giving antacids, metoclopramide,
digoxin or ketoconazole.
Sucralfate
Clinical applications
Sucralfate is indicated for the symptomatic treatment
of gastric ulceration from various causes. In humans,
sucralfate is as effective as antacids or H 2 -receptor
antagonists in healing ulcers. It does not appear to be
successful, however, in preventing corticosteroid-induced
ulceration in dogs subjected to spinal surgery. Its efficacy
in preventing NSAID-induced ulcers is unproven
in the dog. Sucralfate has also been used to treat oral
and esophageal ulcers and esophagitis.
Mechanism of action
Sucralfate is composed of sucrose octasulfate and aluminum
hydroxide, which dissociate in the acid environment
of the stomach. Minimal systemic absorption
of either compound occurs. Sucralfate is structurally
related to heparin but does not possess any appreciable
anticoagulant activity. It is also structurally related to
sucrose but is not used as a sugar by the body.
When given orally, sucrose octasulfate reacts with
hydrochloric acid and is polymerized to a viscous sticky
substance that binds to the proteinaceous exudate
usually found at ulcer sites. Because of electrostatic
charges, sucralfate preferentially adheres to ulcerated
tissues. It protects the ulcer against hydrogen ion backdiffusion,
pepsin and bile and therefore promotes ulcer
healing. The aluminum hydroxide theoretically neutralizes
gastric acid but this antacid activity is not believed
to be clinically important.
It was believed that the formation of a physical protective
barrier was the major mechanism by which
sucralfate assisted ulcer healing. However, it is now
believed that the major drug actions of sucralfate are
related to stimulation of mucosal defense and reparative
mechanisms, possibly related to stimulation of local
PGE 2 and PGI 2 production. Sucralfate also inactivates
pepsin, adsorbs bile acids and is believed to be
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