Page 89 - JSOM Winter 2017

The clandestine manufacturing and illict trade and use of un- (e.g., W-series, U-series) represent the greatest threat to the ris-
regulated novel synthetic opioids represent a significant chal- ing opioid crisis. 16–21
lenge to public health. Many of these novel synthetic opioids
22
never reached the human market and, therefore, most of these Opioid Receptors and Comparative Potency
drugs do not have any pharmacokinetic or pharmacodynamic
data for use in humans. 11,14,22 As such, the potency and poten- Three main opioid receptors exist in the body: mu (μ), kappa
tial adverse effects of these agents remain unkown. 14,22 Ana- (κ), and delta (δ). The psychoactive effects of opioids result
23
lytical methods for detecting and monitoring these novel drugs from binding and activation of endogenous μ opioid recep-
also remain lacking. 14,22 Standard immunoassay urine toxicol- tors (MOPs) located primarily throughout the brain. 1,23 Opi-
ogy screening in the clinical setting does not detect synthetic oids that primarily bind to, activate, and cause a maximal
opioids. US Food and Drug Administration (FDA)-approved functional response at the MOP are referred to as µ-agonists
opiate immunoassays do not cross-react with the synthetic (e.g., morphine, fentanyl, carfentanil). 1,14,23 As a whole, novel
opioids, and few clinical laboratories offer fentanyl testing in synthetic opioids are highly selective for the MOP receptor.
14
real time. Most often, the only way the use of one of these MOP receptor activation leads to analgesia but also sedation,
14
novel drugs is detected is from an experienced recreational euphoria, respiratory depression, bradycardia, nausea, vomit-
drug user reporting that his or her present drug exposure was ing, and decreased gastrointestinal motility. 23
significantly different from previous accounts using the same
“drug” and same amount. 11,22 All of these facts together pres- Potency is the amount (concentration or dose [mg/kg, μg/kg])
ent a challenge to emergency medical services (EMS) providers of drug required to produce an effect of given intensity. In
28
as well as emergency physicians in regard to early detection of comparison to the natural opiate morphine, the following are
and provision of timely treatment for potential lethal opioid reported comparative potencies :
14
exposures.
• Heroin is 2 to 4 times as potent as morphine. 14
• Fentanyl is about 50 to 100 times more potent than mor-
History of Opioids and Terminology
phine and 30 to 50 times more potent than heroin. 28
Opium is the archetypal compound from which all medicinal • Carfentanil is 10,000 times more potent than morphine
and illicit opioid drugs are either derived from or synthesized and about 100 times more potent than fentanyl. 14
to mimic. 1,23 It is obtained by collecting and drying the milky
juice or latex sap (aka poppy tears, Lachryma papaveris) The potency and clinical effects of illicitly manufactured opi-
that comes from the seed pods of the poppy plant Papaver oids encountered in the field may vary greatly depending on
somniferum. 23,24 For centuries, opium has been used for its the purity of the manufactured opioid-related substances. Be-
euphoric, analgesic, and antianxiety effects. 1,5,24 The pharma- cause many novel synthetic opioids have not been evaluated in
cologically active principles of opium lie within the several people or canines, estimates of relative potency of these drugs
naturally occurring alkaloids found within the opium latex. 1,24 are not completely known.
The major psychoactive alkaloids include morphine (approxi-
mately one-tenth the volume of the opium latex), codeine, and Clinical Signs of Opioid Toxicity in OpK9s
thebaine. 23,24 The term opiate refers to all naturally occurring
alkaloids obtained from the opium sap. 25 Opioid toxicity may include dose-related respiratory, central
nervous system, and cardiovascular depression. The greatest
First used in the 1950s, the term opioid, originated from adverse risk is severe respiratory depression leading to respira-
combining the words “opium” + “-oid” (Greek derivations: tory arrest, coma, and death. Canines tend to have a higher
“opium” = opioin [poppy juice] + “-oid” = eidos [form]). tolerance (less susceptible) for opioid-induced respiratory de-
26
Originally, opioid referred only to the semisynthetic and syn- pression than do humans. 28–30 Opioid-induced dysphoria (rest-
thetic drugs manufactured to provide opium-like effects. 25,27 lessness, howling, whining, panting) is a commonly reported
As a modern-day term, opioid defines a class of drugs that side effect in canines and may serve as the first clinical indi-
are either directly derived from (e.g., opium alkaloids) or syn- cation of exposure. Opioid toxicity in canines is primarily
31
thetically manufactured to act like opium by binding to opioid manifested clinically by 28–30 :
receptors in the body. 25–27 In a broader sense, opioid applies to
“any substance, endogenous or synthetic, peptidic or nonpep- • Low heart rate (bradycardia)
tidic, that produces morphine-like effects through action on • Low blood pressure (hypotension)
opioid receptors.” 9,25 • Pinpoint pupils (miosis)
• Hypothermia
From the opium alkaloids, various semisynthetic and synthetic • Progressive respiratory depression (slow to absent breath-
drugs with similar psychoactive properties have been manu- ing) and hypoventilation
factured or synthesized for medicinal and/or illicit recreational • Altered mental status (continuum of mild sedation to
use. 9,14,16,23 Semisynthetic and synthetic opioid drugs are com- comatose)
pounds not found in nature. Semisynthetic drugs, such as hy-
dromorphone, oxymorphone, hydrocodone, and oxycodone, Routes and Formulations of Exposure
are produced by combining an opium alkaloid with a syn-
thetic compound. Synthetic opioid drugs (e.g., fentanyl, fen- OpK9s are at particular risk for encountering illict opioids
tanyl analogues, oxycontin, the U-series opioids, methadone, during routine activities such as drug raids and search war-
and others) possess opium-like effects but do not contain any rants. Drugs may be found lying out in the open (on a table or
opium; they are synthesized in a laboratory setting purely counter) or concealed in innocuous devices such as eye drop-
from chemicals. 14,23 As mentioned, novel synthetic opioids pers and hair spray containers. Possible routes of accidental

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