Page 429 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

396 SECTION | IV Drugs of Use and Abuse

VetBooks.ir Common street names for cocaine HCl include “bernies,” Volmer, 2005). Up to 20% of a dose of cocaine is
excreted unchanged in the urine. Benzoylecgonine and
“blow,” “C” or “big c,” “coke,” “girl” or “white girl,”
ecgonine methyl ester are the primary metabolites
“gold dust” or “star dust,” “her,” “lady” or “white lady,”
“nose candy,” “snow,” or “toot.” excreted in the urine of most mammals in both conjugated
Cocaine HCl is converted to the free alkaloid by dis- and unconjugated forms (Kollias-Baker et al., 2003).
solving it in a basic solution, which is then boiled to pre- Other metabolites include norcocaine, benzoylecgonine,
cipitate the alkaloid. The dry precipitate is broken into norecgonine, and ecgonine. Kollias-Baker et al. (2003)
“rocks” which are 75% 90% pure, and often subse- found cocaine in the urine for up to 24 h when horses
quently diluted with inert ingredients or active compounds were dosed sublingually with 2.5 mg. Larger doses are
such as procaine, lidocaine, amphetamines, heroin, caf- detectable for a few days.
feine, phencyclidine, ergot alkaloids, and strychnine. The
free base readily vaporizes with heat and the smoke is Mechanism of Action
inhaled, though it may be taken orally. This form of
Cocaine increases release of catecholamines and blocks
cocaine is termed “crack” because of the sound produced
reuptake of NE, serotonin, and dopamine, leading to
when it is heated, but it is sometimes called “bedrock,”
increased neurotransmitter concentrations at synaptic
“beamers,” “BJ’s,” “bolo,” “crank,” “crystal,” “flake,”
junctions (Kisseberth and Trammel, 1990; Volmer, 1995;
“ice,” “jelly beans,” “rock,” “rooster,” “space,” “tornado,”
Queiroz-Neto et al., 2002; Vroegop et al., 2009). NE reg-
or “24/7.”
ulates thalamic effects on appetite, body temperature, and
Exposure to illicit cocaine is most likely to affect
sleep. Cocaine also influences the endogenous opiate sys-
dogs, particularly police dogs, but it’s also been used in
tem. Local anesthetic actions occur through inhibition of
racing greyhounds. Athletic horses are also sometimes
membrane sodium ion channels.
dosed with cocaine to improve performance
Cardiac effects are often associated with IV dosing of
(Dumonceaux and Beasley, 1990; Kisseberth and
cocaine (Kabas et al., 1990; Kisseberth and Trammel,
Trammel, 1990; Frazier et al., 1998; Queiroz-Neto et al.,
1990). Cocaine acts directly on myocardium by blocking
2002; Kollias-Baker et al., 2003; Volmer, 2005). A clini-
sodium ion channels, thus causing conduction distur-
cal study found that 8 of 19 dogs that presented for
bances and prolonged R waves. Cocaine increases cal-
cocaine toxicosis were also exposed to THC (Thomas
cium concentrations within cardiac myocytes and can
et al., 2014).
promote depolarization during the diastolic interval lead-
ing to ventricular fibrillation. Cocaine slows conductance
Toxicity at the bundle of His. Oxygen demand is increased within
The LD 50 for cocaine in dogs is 3 mg/kg IV, and the the myocardium but constriction of the coronary vascula-
LD 99 is 20 mg/kg IV. Dogs can tolerate two to four times ture leads to hypoxia and infarction (Kabas et al., 1990;
the above doses if it is given PO. The minimum lethal Volmer, 2005; Vroegop et al., 2009).
dose in cats is approximately 7.5 mg/kg IV or 16 mg/kg
SC. Horses given 50 mg of cocaine IV showed no clinical Clinical Signs
signs, but performance was enhanced at 200 mg (Kollias-
Clinical signs of cocaine toxicosis are associated with
Baker et al., 2003).
CNS stimulation, sometimes followed by depression
(Kisseberth and Trammel, 1990). Clinical signs described
Toxicokinetics in dogs admitted to an emergency clinic for cocaine toxi-
Cocaine is highly lipophilic and readily absorbed from all cosis include muscle tremors (7/19), ataxia (4/19), and
mucosal surfaces, including those of the nose, oral cavity, hyperesthesia or hyperexcitability (3/19). Other com-
gastrointestinal tract, and alveoli. Approximately 20% of plaints included altered mentation, seizures, licking,
an ingested dose is absorbed. Peak plasma concentrations vocalization, hypersalivation, vomiting, and nystagmus.
appear between 15 min and 2 h after ingestion and Mydriasis (11/19), tachcardia (10/19), obtundation (6/19),
cocaine readily crosses the blood brain barrier. The neu- hypertension (4/19), seizures (2/19), anisocoria, ptosis,
rological effects of cocaine and crack last for 15 20 min and blindness were noted on physical examination or dur-
after insufflation or 5 10 min after smoking recreational ing hospitalization of affected dogs (Thomas et al., 2014).
doses. Cardiac changes are consistently reported. Dogs dosed IV
Cocaine undergoes hydrolysis by plasma esterases to with cocaine had increased heart rate, cardiac output, and
water soluble metabolites benzoylecgonine, ecgonine mean arterial pressure (Catravas and Waters, 1981).
methyl ester, and others (Queiroz-Neto et al., 2002). Electrocardiographic changes were absent in the clinical
Hepatic esterases and demethylating enzymes play a role study but have been described to include increased dura-
in cocaine metabolism (Kisseberth and Trammel, 1990; tion of QRS complexes and P-wave abnormalities (Llera