Page 431 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

398 SECTION | IV Drugs of Use and Abuse

VetBooks.ir for the stimulation of medullary respiratory centers in 1 3 h after ingestion, unless a sustained release product
Historically, amphetamines were used by veterinarians
Peak plasma concentrations of amphetamine occur
was ingested. Amphetamines are highly lipid soluble and
order to increase respiratory rate and depth in animals
(Adams, 2001). These drugs are not currently used in vet- readily cross the blood brain barrier (Volmer, 2005).
erinary medicine. Physicians have used amphetamines to Concentrations in the cerebral spinal fluid can be 80% of
control appetite in obese patients, to treat narcolepsy, those found in the plasma (Kisseberth and Trammel,
depression, alcoholism and, counter-intuitively, to control 1990). Methamphetamine has increased partitioning to the
hyperkinetic behavior in children. Most are sold as tablets CNS compared to other amphetamines (Rimsza and
or capsules, which may be sustained release (Kisseberth Moses, 2005). Amphetamine is also distributed to the kid-
and Tremmel, 1990). One study found that 5% of eighth neys, liver and lungs, with negligible storage in the adi-
grade students in the United States and 7% of high school pose tissue (Baggot and Davis, 1972).
students surveyed had used amphetamines over a 1 year There is significant hepatic metabolism of ampheta-
period (Latimer and Zur, 2010). mines. The two major pathways are hydroxylation and
Amphetamines on the illegal market are sold as “ben- deamination. Deaminated products can be oxidized and
nies,” “dex” or “dexies,” “speed,” or “uppers.” conjugated to glycine (Baggot and Davis, 1972). Active
Prescription products may find their way to the illegal metabolites are produced. Amphetamine and its metabo-
market, but many “designer” amphetamines such as meth- lites are excreted primarily in the urine and minimally in
amphetamine are created in clandestine laboratories. the bile. About 8% of an amphetamine sulfate dose is
Crystal methamphetamine, called “ice” or “glass,” may excreted unchanged in the urine in swine and 30% in
be smoked; powdered methamphetamine, termed “crank” dogs. The rate of excretion is significantly increased as
or “meth,” may be dosed intravenously, orally, or insuf- urine pH declines (Baggot and Davis, 1972; Kisseberth
flated (Rimsza and Moses, 2005; Anonymous, 2011). and Trammel, 1990; Volmer, 2005). Amphetamine is
“Yaba” contains methamphetamine and caffeine. A sur- almost completely eliminated within about 6 h in dogs
vey found that about 4% of US high-school students have with an average urinary pH of 7.5, and in 3.3 h if the uri-
used methamphetamine (Eaton et al., 2010). Other nary pH averages around 6.0.
“designer” amphetamines include 4-methylaminorex, sold
as “euphoria,” “U4EUH,” or “ice,” MDEA, sold as Mechanism of Action
“Eve,” methylcathinone (see Khat) and MDMA. Drug
Questions remain concerning the mechanism of action of
dealers may combine amphetamine with inert or other
amphetamines. Sympathetic central and peripheral effects
active ingredients or may substitute other drugs such as
are because of direct actions on α and β adrenergic recep-
heroin, cocaine, or phenylethylamine.
tors, increased release of catecholamines, particularly NE,
Accidental ingestion of prescription amphetamines is
inhibition of monoamine oxidase (MAO), and inhibition
the most likely exposure risk for companion animals, but
of catecholamine reuptake (Kisseberth and Trammel,
potential exists for exposure of companion animals to ille-
1990; Adams, 2001; Diniz et al., 2003; Volmer, 2005;
gal drugs. Illegal doping is a possible exposure risk for
Llera and Volmer, 2006). Amphetamines also promote
equine and canine athletes.
serotonin and dopamine release and act directly on dopa-
mine receptors.
Toxicity
Catravas et al. (1977) found that 10 mg/kg IV amphet- Clinical Signs
amine killed dogs within 3 h. LD 50 s for orally adminis-
Common clinical signs of amphetamine toxicosis in ani-
tered amphetamine sulfate and methamphetamine in dogs
mals include mydriasis, hyperactivity, restlessness, tre-
are 20 27 mg/kg and 9 100 mg/kg, respectively (Diniz
mors and seizures, circling and other stereotypic
et al., 2003; Volmer, 2005).
repetitive behaviors, and occasionally ataxia and depres-
sion. Hyperthermia can be secondary to seizures and
Toxicokinetics peripheral vasoconstriction. Tachycardia and ventricular
Absorption of amphetamines through the gastrointestinal premature contractions, hypertension, or occasionally
system is usually rapid, though it is slower with sustained hypotension, have all been observed. Other reported
release products (Dumonceaux and Beasley, 1990; symptoms are mydriasis, hypersalivation, vocalization,
Kisseberth and Trammel, 1990; Dumonceaux, 1995; bloody diarrhea, and petechiation of the abdominal skin
Volmer, 2005). Methamphetamine absorption is more (Fitzgerald and Bronstein, 2013).
rapid by insufflation, with onset of clinical signs in Reported causes of death in amphetamine overdosed
2 5 min; whereas, the onset after PO dosing is dogs include disseminated intravascular coagulation
15 20 min (Anonymous, 2011). (DIC) secondary to hyperthermia and respiratory failure