Page 410 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Over-the-Counter Drugs Chapter | 21 377

VetBooks.ir Mechanism of Action effects include dry mucous membranes, fixed and dilated
pupils, tachycardia, and arrhythmia, and animals can be
Antihistamines act by competitive inhibition of histamine
either hypertensive or hypotensive. Cardiac abnormalities
at H 1 receptors (Papich, 1990; Gwaltney-Brant, 2004).
Binding is reversible, but can become irreversible or slow were documented in humans and dogs that ingested terfe-
to dissociate at high doses, as with terfenadine (Otto and nadine (Otto and Greentree, 1994; Gwaltney-Brant,
Greentree, 1994; Gwaltney-Brant, 2004). H 1 receptors are 2004). Animals can have allergic reactions to topical or
found in a variety of tissues, including the mast cells of oral antihistamines. A list of associated clinical signs
includes dermatitis, pyrexia, and photosensitization
the skin, the smooth muscle of airways, gastrointestinal
(Gwaltney-Brant, 2004). Teratogenic effects have been
tract, urogenital tract, and cardiovascular system, the
detected in experimental animals treated with piperazine.
endothelial cells and lymphocytes, and the mammalian
Metabolic acidosis and electrolyte abnormalities have
CNS. Histamine produces dermal itching and allergic
been documented based on serum chemistry of
responses in the skin and contraction of smooth muscle in
antihistamine-overdosed animals, but overall changes are
the bronchial tree and intestine. Low doses of histamine
nonspecific. Changes reported on postmortem examina-
produce a rapid onset of vascular dilation. The wheal-
tion also tend to be nonspecific. Rhabdomyolysis, and
and-flair reaction associated with histamine release is due
associated renal lesions, or DIC are possible complica-
to increased vascular permeability. Histamine in the CNS
tions of antihistamine toxicosis.
modulates sleep/wake cycles.
Antihistamines are used to block allergic response and
reduce itching. Antihistamines block smooth muscle Management
contraction, reducing bronchoconstriction, and affecting
Diagnosis of antihistamine toxicosis is usually based on
vascular and uterine smooth muscle. Effects on intestinal
history and clinical signs. Laboratory testing of urine or
smooth muscle can cause gastrointestinal disturbances.
plasma can be helpful to confirm exposure, but results
Antihistamines also prevent increased vascular permeability
will be delayed for hours or days, and quantitation is
associated with histamine release. CNS effects produced by
unlikely to be of value.
antihistamines can include sedation or excitement.
Emetics are appropriate to promote gastric emptying
Muscarinic stimulation is believed to be involved in
in asymptomatic animals after large, recent ingestions of
motion sickness-induced vomiting. The antimuscarinic
actions of antihistamines decrease nausea and vomiting antihistamines, but caution is advised because onset of
(Papich, 1990). Gastrointestinal motility is decreased, and clinical signs can be rapid. Gastric lavage of the anesthe-
respiratory suppression is sometimes seen with antihista- tized, intubated animal is more appropriate in symptom-
mines. Phenothiazine-type antihistamines also block atic patients. Activated charcoal and a cathartic can be
α-adrenergic receptors. Allergic reactions to antihista- instilled after lavage, or given to the stable patient.
mines have been noted. Multiple doses of activated charcoal have been recom-
mended to interrupt enterohepatic cycling.
Drugs such as penicillin G and NSAIDs have been
Clinical Signs recommended to reduce protein binding and enhance
Clinical signs of antihistamine overdose are usually evi- excretion (Tegzes et al., 2002). However, in the short
dent within 30 min of dosing. Signs of CNS depression term, this can worsen clinical signs.
can occur with therapeutic doses of first-generation anti- Serum chemistry should be assessed and monitored for
histamines, and include sedation, ataxia, and drowsiness. hydration, electrolyte balance, acid base status, and liver
More severe clinical signs, such as profound depression, and kidney function. Animals with poor hepatic or renal
coma, respiratory suppression, convulsions, and myocar- function can eliminate antihistamine more slowly
dial depression, can lead to death (Buchweitz et al., (Gwaltney-Brant, 2004). Cardiac function, blood pressure,
2014). A dog with hydroxyzine toxicosis presented with and body temperature should be monitored, and respiratory
tachycardia and weakness progressing to stupor, coma, function should be closely monitored, because intubation is
loss of gag reflex, and apnea (Tegzes et al., 2002). Higher sometimes required to support the comatose patient.
doses of antihistamines can have a stimulatory effect on Fluid therapy is useful to maintain hydration for car-
the CNS, particularly in children and young animals. diac support, diuresis, and correction of pH and electro-
These effects are less common in adults. Overdosed lyte imbalances. Animals rarely require treatment for
young individuals appear to experience hallucinations, hypotension or mild-to-moderate cardiac arrhythmias,
lack of coordination, disorientation, irritability, anxiety, which usually respond to fluid therapy. Epinephrine
aggression, seizures, and pyrexia. should not be used in promethazine overdose (Staley and
Salivation, vomiting, and diarrhea have been associ- Staley, 1995). Promethazine inhibits adrenergic receptors,
ated with first-generation antihistamines. Anticholinergic and addition of epinephrine can lead to further decrease