Page 407 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

374 SECTION | IV Drugs of Use and Abuse

VetBooks.ir MAO inhibitors, halothane, and methylxanthines (Means, Stimulation of α-1 receptors causes vasoconstriction and
Sympathomimetic amines can interact with digoxin,
subsequent drying of the mucous membranes of the nasal
mucosa and sinuses. Ophthalmic solutions decrease eye
1999, 2005; Ooms and Khan, 2001). Certain conditions are
known to predispose animals to adverse reactions when redness by constriction of conjunctival and scleral vascu-
given sympathomimetic amines. These include diabetes, lature. Peripheral vasoconstriction leads to increased sys-
hypothyroidism, hyperthyroidism, cardiac disease, hyperten- temic vascular resistance and hypertension. Stimulation of
sion, seizure disorders, renal disease, and glaucoma. the α-1 receptor can cause vasospasm of the coronary
artery and myocardial necrosis. Other α-adrenergic effects
Toxicity may include appetite suppression, CNS stimulation, and
mydriasis. The effects of phenylephrine and oxymetazo-
Pseudoephedrine is used as a treatment for urinary inconti-
line are α-receptor-specific. Stimulation of α-receptors by
nence in dogs because it improves urethral sphincter. The
PPA causes release of endogenous catecholamines in the
dose is usually 1 2 mg every 12 h (Means, 2005). Clinical
brain and heart, and can inhibit MAO at high doses.
toxicosis has been reported in dogs given 5 6 mg/kg,
Stimulation of β-receptors is the cause of some of the
and death was documented in dogs given 10 12 mg/kg
cardiac effects attributed to decongestants, which include
(Means, 1999, 2005; Ooms and Khan, 2001).
increased contractility and output, increased heart rate,
Drugs containing ephedrine, in the form of ma huang,
and tachyarrhythmia. Reflex bradycardia is possible.
are often combined with caffeine, in the form of guarana.
Bronchodilation is also mediated through β-receptors.
This combination of drugs acts synergistically, enhancing
the toxicity of this product. Doses of 1.3 88.9 mg/kg ma
huang given concurrently with 4.4 296.2 mg/kg guarana Clinical Signs
have been associated with clinical toxicosis in dogs. One
CNS stimulation is the common presentation for animals
dog given a dose of 5.8 mg/kg ma huang and 19.1 mg/kg
with decongestant overdose. Hyperactivity, restlessness, agi-
guarana died. There seems to be great individual differ-
tation, pacing, and vocalization are reported (Papich, 1990;
ence in sensitivity to this combination of drugs, and prog-
Means, 1999, 2005). Hallucinatory behaviors in dogs include
nosis is also dependent on the time that elapses between
staring into a corner or at unseen objects, perhaps even bit-
exposure and treatment (Ooms and Khan, 2001).
ing at them. Tremors, seizures, and head-bobbing can be
The therapeutic dose of PPA for urinary incontinence
observed. Hyperthermia can be secondary to increased activ-
in dogs is 1.1 mg/kg (Crandell and Ware, 2005; Means,
ity, and DIC or rhabdomyolysis with associated renal failure
2005). Clinical signs of irritability, tachycardia, hyperten-
are possible outcomes. Cardiovascular changes include
sion, and urinary retention have been observed at the ther-
tachycardia, reflex bradycardia, and hypertension. Blood
apeutic dose (Ginn et al., 2013). Elevated blood pressure
pressure can remain elevated in dogs for 6 h. Animals can
was seen in beagles given 3.1 mg/kg PO every 8 h, and
die from cardiovascular collapse. Vomiting, diarrhea, dehy-
myocardial damage was noted in a dog given 48 mg/kg.
dration, and anorexia were reported in one dog with PPA
Pharmacokinetics toxicosis, along with ataxia, lethargy, tachycardia, and
tachypnea. Pupils were bilaterally dilated with loss of pupil-
Decongestants are rapidly absorbed by the gastrointestinal
lary light reflex and vertical nystagmus. This dog was not
tract (Papich, 1990; Means, 2005). Ephedrine is absorbed
hypertensive at presentation to the veterinarian 12 h after
within 2 h of ingestion (Ooms and Khan, 2001). The onset
ingestion (Crandell and Ware, 2005). Another dog was trea-
of action is usually within 30 min, although it is delayed up
ted for hypertension and tachycardia after ingesting a dose
to 8 h with extended-release products. Sympathomimetic
of PPA greater than 50 mg/kg (Ginn et al., 2013). The dog
amines are believed to cross the blood brain barrier
had a markedly elevated creatinine kinase indicating muscle
(BBB) and the placenta, and are known to be secreted into
damage, and cardiac troponin 1 indicating myocardial dam-
milk. Metabolism occurs primarily in the liver. Most of a
age, hypertensive retinopathy, retinal detachment, and devel-
dose of ephedrine is excreted unchanged in the urine, and
oped oral mucosal ulcers during hospitalization, which
other decongestants are excreted 55% 75% as the parent
resolved after recovery.
compound. The elimination half-life of pseudoephedrine is
Ooms and Khan (2001) studied dogs accidentally
2 21 h; 2 4 h for PPA. Urinary excretion is accelerated
overdosed with a combination of ma huang and guarana
with low urine pH (Ooms and Khan, 2001; Means, 2005).
herbal preparations, and found that the onset of clinical
signs could be as early as 30 min after ingestion, and was
Mechanism of Action usually within 8 h. Duration of signs ranged from 10 to
Adrenergic stimulation is responsible for the effects pro- 48 h. Vomiting was seen in 47% of dogs, 5% were
duced by decongestants (Papich, 1990; Means, 1999, anorexic, 30% were tachycardic, 6% were tachypneic,
2005; Ooms and Khan, 2001; Crandell and Ware, 2005). 21% had mydriasis, 27% had tremors, 6% had behavioral