Page 236 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Nervous System Toxicity Chapter | 12 203

VetBooks.ir effects opposite those of α 1 stimulation, namely hypoten- tranquilizers such as acepromazine and chlorpromazine
are the mainstay of sympathomimetic overdose therapy
sion. Stimulation of β 1 receptors, located predominantly
due to their postsynaptic blocking effects of dopamine as
in the heart but also in the kidney, adipose, skeletal mus-
cle, and eye, results most notably in an increase in the well as inhibition of its release and increase in its turnover
rate and force of cardiac contraction. The β 2 adrenergic in the CNS. Phenothiazines also block α adrenergic and
receptors (present in skeletal muscles, the smooth muscle cholinergic activity and are antihistaminic (Plumb, 2015;
of the bronchi, vasculature and uterus, and the liver) Means, 2004).
mediate vasodilation, bronchodilation, uterine relaxation,
and enhanced glycogenolysis in the liver (Landsberg and Serotonin
Young, 2001).
Examples of adrenergic toxicosis involving overstimu- Serotonin (5-hydroxytryptamine) synthesis involves
lation of the α 2 receptors include: accidental ingestion of the conversion of the amino acid tryptophan to 5-hydro-
brimonidine, the active ingredient in Alphagan eye drops xytryptophan (5-HTP) followed by the conversion of 5-
used in the treatment of glaucoma; ingestion of amitraz- HTP to 5-hydroxytryptamine. The various physiologic
containing Preventic collars; ingestion of clonidine, a roles of serotonin include regulation of sleep, mood, cog-
human medication used for hypertension and other indica- nition, appetite, and behavior (Spencer, 2000). Because of
tions; and overdosage of the sedative/analgesic xylazine. the popularity of selective serotonin reuptake inhibitors
Exposures involving Alphagan typically involve punctur- (SSRIs) in human and veterinary medicine and over-the-
ing of the bottle with sparing amounts actually ingested. counter supplements containing 5-HTP for the treatment
Clinical signs for all four toxicoses include profound of depression in humans, accidental overdoses are com-
hypotension and bradycardia, which can be specifically mon in veterinary medicine. Examples of SSRIs include
reversed with either of the α 2 antagonists, yohimbine or fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine
atipamezole (Antisedan). Patients should be closely moni- (Paxil) and sertraline (Zoloft) (Plumb, 2015). The seeds
tored for recurrence of signs once the effect of the antago- of the West African legume Griffonia simplicifolia con-
nist wears off. The half-life of atipamezole in dogs is tain 5-HTP. The clinical picture of serotonin excess,
longer than yohimbine and may require less frequent termed serotonin syndrome, includes tremors, seizures,
administration (Plumb, 2015; Mensching, 2011). hyperthermia, depression (rarely to the point of coma), dis-
An example of adrenergic toxicosis involving over- orientation, vocalization, hyperesthesia, ataxia, tachycardia,
stimulation of the β 2 adrenergic receptors involves the hypertension, agitation, vomiting, and diarrhea. Treatment
accidental puncture by chewing on a pressurized albuterol of the clinical patient is largely symptomatic and support-
inhaler. Albuterol is a β 2 adrenergic agonist used thera- ive, but the serotonin antagonist cyproheptadine specifi-
peutically to treat the bronchoconstriction associated with cally mediates the effects of serotonin syndrome. The drug
asthma. When excessive β 2 stimulation occurs, profound can be given orally or crushed, mixed with water or saline,
hypotension, a reflex tachycardia, and subsequent release and administered rectally at a dosage of 1.1 mg/kg in dogs
of catecholamines can occur. Clinical signs usually (Gwaltney-Brant, 2004a).
include tachycardia with possible ventricular premature
contractions, tachypnea, hyper- or hypotension (depend- Glycine
ing on the timeframe relative to exposure and the predo-
minating neurotransmitter effect), behavioral changes Glycine is an inhibitory neurotransmitter that is synthe-
including restlessness, agitation, anxiety, largely due to sized from serine. Glycine acts predominantly in inter-
secondary catecholamine release, weakness later in the neurons (Renshaw cells) of the brainstem and spinal cord
course, and hypokalemia, sometimes severe, because of as well as in spinal sensory, auditory, and visual path-
an intracellular potassium shift. Treatment is largely sup- ways. Two well-known toxicants, tetanus and strychnine,
portive with fluid therapy, management of severe tachy- act by inhibiting glycine’s inhibitory effects.
cardia with a β blocker such as propranolol, Tetanospasmin, a biotoxin produced by the anaerobic bac-
supplementation of potassium as needed, and diazepam to terium Clostridium tetani, is responsible for the preven-
address behavioral changes due to secondary norepineph- tion of glycine release (Roder, 2004b). The ubiquitous
rine release (Mensching and Volmer, 2007). bacterial spores typically enter through a puncture or
Sympathomimetics such as amphetamines, cocaine, other anaerobic wound. The lack of glycine inhibition
pseudoephedrine, phenylpropanolamine and ma huang results in unchecked muscle contraction, largely of the
mediate dopaminergic and norepinephrine-induced neuro- powerful extensor muscles of the limbs and the masseter
toxic effects including hypertension, hyperexcitability, muscles. The stereotypical sawhorse stance and “lockjaw”
tachycardia, tremors, seizures, mydriasis, hyperesthesia, result within 5 10 days of wound infection. Less severe
head-bobbing, piloerection, and death. Phenothiazine signs include elevation of the nictitating membrane,