Page 90 - JSOM Winter 2017

exposure for OpK9s include inhalation (through the respira- called first-pass metabolism. 40-42 As such, ingestion of a small
tory tract), transdermal (through the skin), oral (ingestion), amount of opioid tends to present a very low exposure risk for
and oral transmucosal (across the buccal membrane). Inha- OpK9s. Oral transmucosal (OTM) or transbuccal absorption
lation or respiratory exposure is the most likely exposure is possible in canines but is affected by factors such as the
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route, with transdermal exposure being the second most likely pH and formulation of the drug as well as the dwell or contact
route. 32–34 time within the buccal pouch. In canines, fentanyl has OTM
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bioavailabilities ranging from 20% to 50% depending on the
Illicit opioids are found as powders, blotter paper, liquids, na- pH of the solution. Although several OTM fentanyl formula-
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sal sprays, and pills. 10,33,34 During a raid or drug search, an tions are approved for use in humans, these products are not
OpK9 may accidentally bite and/or ingest whole bags of drugs currently used extra-label in canines. 28
that may rupture and induce a massive exposure ; they may
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lap up opioid solutions resulting in oral and oral transmucosal Opioid Exposure Risk in OpK9s
(buccal) exposures; or they may inhale small amounts of pow-
dered drug. A dry powder is the most likely and probably most Due to the wide array of pharmaceutical and illicitly manu-
hazardous form a first responder, and similarly an OpK9, may factured opioids available on the market, a large variation
encounter in the field. 33,34 Synthetic opioid powders have a in the levels of toxicity for each drug exists for animals.
particulate size ranging from 0.2 to 2.0 mm and are easily The minimum lethal dose reported for morphine is 110mg/
34
aerosolized when disturbed (e.g., “burping” sealed contain- kg intravenous (IV) and 210mg/kg subcutaneous (SC). For
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ers, deploying flash bangs); therefore, powders present a high heroin, the minimum lethal dose is 25mg/kg SC. At approxi-
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inhalation risk. When an OpK9 contaminated with an opioid mately 0.2mg/kg IV, heroin causes sedation and respiratory
powder “shakes” or brushes up against something, the pow- depression, whereas 0.58mg/kg IV led to increased duration
der residues are readily dispersed into the air. This presents a of effects, respiratory difficulty, and aggressive behavior with
significant inhalational exposure hazard to the canine as well clinical signs lasting up to 8 hours. 44
as any nearby personnel.
In conscious dogs, safety studies demonstrate that fentanyl has
a wide margin of safety. 28,30 Available scientific evidence and
Factors Affecting Drug Absorption and Relative
Exposure Risk professional clinical experience support the fact that canines
tend to have a higher tolerance (less susceptibility) for opioid-
The specific drug involved (heroin versus fentanyl versus induced respiratory depression than do people. IV doses up
30
carfentanil), the drug formulation (e.g., powder, liquid, aero- to 3mg⁄kg (approximately 600 times the recommended dose
sol), amount, concentration, and route of drug exposure en- 0.005mg⁄kg) invoked minimal effects on the cardiovascular and
countered determine the exposure risk. Absorption across respiratory systems. A single dose of a transdermal fentanyl
28
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the nasal mucosa via inhalation is rapid and may result in high solution, administered at 3 to 5 times the recommended dose
drug bioavailability depending on the drug formulation (e.g., in canines, did not result in any fatality and caused minimal
powder versus spray mist). 36-38 changes in respiratory rates, oxygen consumption, and blood
gas analysis. All dogs fully recovered from the transient nar-
30
Transdermal absorption requires direct skin contact of a large cotizing effects with only minimal supportive care and with-
or highly concentrated and localized amount of drug for a out naloxone reversal. In whole, the data collected from these
long duration. Absorption of opioid powders transdermally studies indicate that respiratory depression (hypoventilation)
tends not to present a significant exposure risk for OpK9s is a safety aspect of limited concern following fentanyl admin-
with intact, unbroken skin. In general, powders settle atop istration to dogs. 28,30 No data are currently available evaluat-
the OpK9’s hair coat, where a large proportion never actu- ing pharmacokinetics or the toxic or lethal dose of carfentanil
ally comes into direct contact with the skin. Subsequently, the or the other aforementioned novel synthetic opioids in canines
powder is either dispersed into the air when the OpK9 shakes (or humans).
or when the OpK9 brushes up against surrounding objects.
In addition, canines do not possess functional eccrine sweat To date, there are a few anecdotal reports of OpK9s becoming
glands dispersed throughout their body like people ; there- clinically effected by a “suspect” opioid exposure during law
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fore, this potential pathway for transdermal drug absorption enforcement activities ;the actual illicit agent (if any) involved
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is not a siginificant risk in canines. were not absolutely confirmed. A review of 652 canine single-
agent home exposures to fentanyl (ingestion of transdermal
Absorption of a powder through the paw pads is also an un- patches and lozenges) reported to the ASPCA Animal Poison
likely route of significant exposure in canines. Paw pads are Control Center (APCC) during 2009–2013 (personal com-
the thickest region of canine skin and are heavily keratinized, munication with Dr Tina Wismer, APCC, 13 August 2017)
providing an effective barrier. Although canines do possess revealed:
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eccrine sweat glands deep within the fat and fibrous tissues of
their digital pads, these tightly coiled, tubular glands are only • Approximately 84% (548/652) displayed signs of exposure.
approximately 25 to 35 μm in diameter. The small pore size • Most common clinical signs included lethargy/sedation
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of these eccrine glands, along with the minutely small propor- (60%), hypersalivation (drooling) (37%), hypothermia
tion of the canines total body surface area, limits the exposure (24%), ataxia (24%), and bradycardia (20%).
risk for transdermal drug absorption through the pads to that
of a dry drug powder. The APCC also reports an increase in heroin exposures in ca-
nines with four exposures reported in 2012 and 22 exposures
Most opioids have a very poor oral bioavailability (e.g., 15– reported in 2016 (personal communication with Dr Tina Wis-
17% for morphine, 33–50% for fentanyl) due to a process mer, APCC, 13 August 2017). Reported clinical manifestations

88 | JSOM Volume 17, Edition 4/Winter 2017