Page 411 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

378 SECTION | IV Drugs of Use and Abuse

VetBooks.ir in blood pressure. Atropine can potentiate the anticholin- H 1 receptor antagonists (or H 1 -blockers) and less likely to
cross the BBB. Ranitidine is about 15% protein-bound.
ergic effects of antihistamines, and is best avoided.
Seizures can be treated cautiously with benzodiaze-
Cimetidine and ranitidine are metabolized predomi-
pines or short-acting barbiturates. The depressive effects nantly in the liver. Seventy-three percent of an oral dose
of antihistamines are additive with these sedatives, and of ranitidine undergoes hepatic metabolism in people,
can produce “rebound depression.” Although cholinergic compared to 40% in dogs. Unchanged cimetidine, famoti-
signs are sometimes present, treatment with physostig- dine, and nizatidine are excreted in the urine. The plasma
mine potentiates cardiovascular dysfunction and seizures, half-life for cimetidine is about 1 h, but can be prolonged
and is contraindicated. in individuals with renal or hepatic insufficiency. The
Animals overdosed with antihistamines usually elimination half-life of ranitidine is 2.5 h in humans and
improve within 24 h, although signs sometimes persist for 4 h in beagles (Boothe, 2001).
up to 3 days. Prognosis is dependent on the severity of
signs, and is guarded in animals presenting with seizures Mechanism of Action
or coma (Gwaltney-Brant, 2004). Tegzes et al. (2002)
H 2 receptor antagonists specifically bind to and block the
report recovery of a comatose dog due to hydroxyzine
actions of H 2 receptors by competitive inhibition. H 2
overdose, though the authors note that supportive care can
receptors are present in the enterochromaffin cells of the
be required for up to 2 weeks.
gastric mucosa. Histamine stimulates acid secretion and,
to a limited extent, pepsin secretion (Adams, 2001;
DRUGS USED TO TREAT Tegzes et al., 2002). High doses of histamine produce a
slow-onset, prolonged vasodilatory response. H 2 receptor
GASTROINTESTINAL SYMPTOMS
inhibitors decrease acid and pepsin secretion. They also
This classification includes antacids, laxatives, and antidi- block some of the cardiovascular effects of histamine
arrheal drugs. (Adams, 2001). Famotidine is nine times more potent as
an H 2 -blocker than ranitidine, which is 5 12 times more
potent than cimetidine. Famotidine also has the longest
Antacids duration of clinical effects (Boothe, 2001). Cimetidine
reduces hepatic blood flow by around 20% and inhibits
H 2 histamine receptor antagonists and mineral antacids are
microsomal cytochrome P450 enzymes, thus it interferes
used to increase gastric pH and reduce discomfort. Use of
with metabolism of other drugs.
these products to aide in healing of gastroduodenal ulcers
secondary to NSAID use is noted in a previous section.
Few adverse effects have been reported with these drugs, Clinical Signs
although contact dermatitis in a horse trainer associated There are no reports of adverse effects in domestic ani-
with ranitidine has been reported (Meani and Nixon, 2015). mals associated with these H 2 receptor antagonists.

Mineral Antacids
H 2 Histamine Receptor Antagonists
An incomplete list of active ingredients in mineral anta-
H 2 histamine receptor antagonists include cimetidine,
cids can be found in Table 21.4. Products may contain
famotidine, nizatidine, and ranitidine. Cimetidine impairs
more than one active ingredient. These products are com-
gastrointestinal absorption of some drugs and prolongs
mon in many households, and may be accidentally
the effects of others by inhibiting their metabolism by
ingested by pets or administered by pet owners. They are
microsomal enzymes.
used in veterinary medicine to decrease gastric hyperacid-
ity and treat peptic ulcers, uremic ulcers, reflux esophagi-
Pharmacokinetics tis, and rumen acidosis secondary to grain overload
Cimetidine is rapidly absorbed, and 70% of a given dose (Boothe, 2001). Few adverse effects are associated with
is bioavailable. Absorption can be slowed by the presence mineral antacids (Papich, 1990). Mineral antacids increase
of food in the stomach. The mean absorption time for gastric pH. Rebound acid secretion can occur when dos-
ranitidine was reported as approximately 1 h, and absorp- ing is discontinued.
tion was not impaired by the presence of food in the stom- Sodium bicarbonate is present in baking soda and in
ach. Ranitidine is 73% bioavailable in dogs and 27% effervescent antacid products. Sodium bicarbonate and cal-
available in horses after oral dosing. Famotidine is poorly cium carbonate are absorbed after ingestion. Transcutaneous
absorbed and only 37% bioavailable. Nizatidine is rapidly absorption of sodium bicarbonate across damaged skin can
and almost completely absorbed (Boothe, 2001). H 2 recep- occur (Gonzalez and Hogg, 1981). Carbon dioxide is pro-
tor antagonists (or H 2 -blockers) are less lipid soluble than duced rapidly when sodium bicarbonate is introduced to an