Postgraduate Medicine
`
`ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: https://www.tandfonline.com/loi/ipgm20
`
`OxyContin® Abuse and Overdose
`
`Christopher T. Aquina, Andreia Marques-Baptista, Patrick Bridgeman &
`Mark A. Merlin
`
`To cite this article: Christopher T. Aquina, Andreia Marques-Baptista, Patrick Bridgeman & Mark
`A. Merlin (2009) OxyContin® Abuse and Overdose, Postgraduate Medicine, 121:2, 163-167, DOI:
`10.3810/pgm.2009.03.1988
`To link to this article: https://doi.org/10.3810/pgm.2009.03.1988
`
`Published online: 13 Mar 2015.
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`OxyContin® Abuse and Overdose
`
`C L I N I C A L F E A T U R E S
`
`Christopher T. Aquina, BS1
`Andreia Marques-Baptista, MD2
`Patrick Bridgeman, PharmD3
`Mark A. Merlin, DO, EMT-P,
`FACEP2
`
`1University of Medicine and Dentistry
`of New Jersey-Robert Wood Johnson
`Medical School, Department
`of Medical Education, New Brunswick,
`NJ; 2University of Medicine and
`Dentistry of New Jersey-Robert
`Wood Johnson Medical School,
`Department of Emergency
`Medicine, New Brunswick, NJ; 3Ernest
`Mayo School of Pharmacy, Rutgers
`University, Piscataway, NJ
`
`Correspondence: Mark A. Merlin, DO,
`EMT-P, FACEP,
`Assistant Professor,
`Emergency Medicine and Pediatrics,
`UMDNJ-Robert Wood Johnson Medical
`School,
`Department of Emergency Medicine,
`51 French St., MEB 104,
`New Brunswick, NJ 08901.
`Tel: 732-235-8717
`Fax: 732-235-7379
`E-mail: merlinma@umdnj.edu
`
`Abstract
`Background: OxyContin® (controlled-release oxycodone hydrochloride) (Purdue Pharma,
`Stamford, CT) was approved in 1995 by the US Food and Drug Administration (FDA) for
`moderate-to-severe chronic pain. Crushing and snorting the delayed-release tablets results in
`a rapid release of the drug, increased absorption, and high peak serum concentrations. The
`propensity for addiction to OxyContin® and the trend of increased prescription drug abuse have
`made it imperative for physicians and health care providers to recognize the clinical presentation
`of overdose and know how to manage associated complications. Objectives: In this review of
`OxyContin®, we discuss current trends in its abuse and the clinical presentation of overdose.
`We review the specifi c effects of the drug on body systems and the recognition of symptoma-
`tology, differential diagnosis, and management. Discussion: Many of the clinical fi ndings
`in acute opioid overdoses are nonspecifi c, making diagnosis diffi cult. OxyContin® overdose
`presents with a typical opiate toxidrome, including decreased respirations, miosis, hypothermia,
`bradycardia, hypotension, and altered mental status. The presence of coingestants can cloud
`the clinical picture. If OxyContin® overdose is suspected, early ventilation and oxygenation
`should be administered, which is generally suffi cient to prevent death. Even in the absence of a
`confi rmation, cautious administration of naloxone—the opiate receptor antagonist and antidote
`for opioid overdoses—may have both diagnostic and therapeutic effects. Summary: With
`increasing rates of prescription drug abuse, OxyContin® will continue to present challenges to
`physicians and health care providers. Physicians should be aware of potential patients who are
`seeking OxyContin® for recreational use.
`
`Keywords: OxyContin®; addiction; substance abuse; overdose; opioid
`
`Introduction
`OxyContin® (controlled-release oxycodone hydrochloride) (Purdue Pharma, Stamford,
`CT) was approved in 1995 by the US Food and Drug Administration (FDA) to treat
`moderate-to-severe chronic pain.1 Oxycodone, the active ingredient in OxyContin®, is
`a schedule II analgesic that acts as a pure opioid agonist on both central and peripheral
`opiate receptors. It has a high bioavailability when administered orally, with a half-life
`of 4.5 hours, and is formulated as a sustained-release tablet. It is designed to provide
`pain relief over a 12-hour period.1,2 The controlled-release property of OxyContin® was
`thought to originally deter abuse when compared with other opioids. In fact, because
`of several preclinical and clinical fi ndings on drugs with slow onsets of action, the
`1997 Physicians’ Desk Reference and the package insert originally stated, “Delayed
`absorption, as provided by OxyContin® tablets, is believed to reduce the abuse liability
`of the drug.”3–7 More recently, US law enforcement offi cials have called OxyContin®
`abuse an “epidemic” and referred to the medication and similar formulation drugs as
`“killers.”8 Crushing and snorting the delayed-release tablets results in the rapid release
`of the drug, increased absorption, high peak serum concentrations, and may precipitate a
`
`© Postgraduate Medicine, Volume 121, Issue 2, March 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
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`Aquina et al
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`fatal overdose.9,10 The propensity for addiction to OxyContin®
`and the trend of increased abuse have made it imperative for
`physicians to recognize the clinical presentation and know
`how to manage complications associated with OxyContin®
`overdose.
`
`Discussion
`Trends in Abuse
`The fi rst cases of OxyContin® abuse were recorded in rural
`areas, including Maryland, eastern Maine, eastern Ohio,
`the “rust-belt” regions of Pennsylvania, and the southern
`Appalachian areas of West Virginia, Virginia, and Kentucky.11
`Abuse continues to be concentrated in rural areas, as well as
`small- to medium-sized urban and suburban areas.7 The drug
`has become known as a “poor-man’s heroin” because of its
`comparatively lower street price than heroin.9 It is commonly
`known as “hillbilly heroin,” “Oxy,” “OC,” or “OxyCotton.”9
`Its abuse does not seem to be as prevalent in inner city urban
`areas where inexpensive heroin is available.7 Abusers often
`obtain the medication in clinics by reporting appropriate
`complaints of chronic pain or by “doctor shopping,” whereby
`they visit different medical practitioners to obtain several
`prescriptions and then get them fi lled at multiple pharma-
`cies to avoid getting caught.9 One study indicated that 70%
`of OxyContin® abusers obtained the drug via a physician’s
`prescription.7 Reports also indicate that some abusers will
`commit fraud and theft, and adolescent abusers will often
`steal the drug from their parents.12–13
`The US Department of Justice reported that 464 deaths
`were linked to OxyContin® overdoses in 2002 and the Drug
`Abuse Warning Network (DAWN) stated that there was
`an estimated 42 810 emergency department (ED) visits
`from oxycodone use in 2005.14–15 A study using a DAWN-
`based classifi cation scheme to analyze the numbers and
`demographics of drug abuse deaths involving oxycodone/
`OxyContin® from August 27, 1999 through January 17, 2002
`found that the average age of death was 39.7 (± 10.6) years
`(range, 9–88 years); 67.2% of the deaths were males. Of the
`reported deaths, 92.9% were white and 3.1% were black.16
`Similarly, an analysis of the demographics of OxyContin®
`abuse by Cicero et al found the average age of abuse to be
`34 years.7 Men were much more likely (⬎ 65%) to abuse
`the drug than women, and 91% of the users were white. Less
`than 5% were black and ⬍ 3% were Hispanic.7
`Oxycodone overdoses often involve polysubstance
`abuse.17 In one study, of the patients who died from
`OxyContin® abuse and overdose, 96.7% had taken multiple
`drugs.16 It was determined via toxicological testing that
`
`56.5% were using concomitant benzodiazepines, 40.1%
`were taking antidepressants, and 27.1% were abusing
`illicit drugs.16 Of those patients who presented to the ED
`for oxycodone abuse in 2002, 71% of the visits included
`the simultaneous use of other drugs.18 The most prevalent
`coingestions were ethyl alcohol (33%), benzodiazepines
`(21%), and cocaine (12%).18
`Several studies and surveys have indicated that OxyContin®
`abuse is increasing at an alarming rate.7,8,11,13,15,19 The
`“Monitoring the Future Study” by National Public Radio
`online and the University of Michigan published an alarming
`statistic that OxyContin® use by 12th graders went up 40%
`between 2002 and 2005, with 5.5% of 12th graders abusing
`the drug in 2005.19 The DAWN report concluded ED visits
`from nonmedical use of oxycodone increased nearly 15%
`between 2004 and 2005 while nonmedical use of pharmaceu-
`ticals in general increased 21% between those same 2 years.15
`These statistics, along with similar fi ndings in a study on the
`trends in OxyContin® abuse, indicate that OxyContin® abuse
`is substantial but seems to be following the general trend of
`increased prescription drug abuse.7,15 Additionally, ⬎ 87% of
`OxyContin® abusers in 1 study had current and past histories
`of substance abuse, signifying that few legitimate patients
`become addicted to the drug if used as prescribed.7
`
`Clinical Presentation of OxyContin®
`Abuse and Overdose
`Pure OxyContin® overdose presents with a typical opiate
`toxidrome, including decreased respirations, miosis, hypo-
`thermia, bradycardia, hypotension, and altered mental status.
`The presence of coingestants can cloud the clinical picture.
`Further, the route of administration infl uences the pharma-
`cokinetic and pharmacodynamic effects of the drug and
`ultimately the clinical presentation and hospital course.
`Opioid overdose causes respiratory depression via both
`reduced hypercarbic and hypoxic respiratory drive.20,21 By
`binding to μ
`2 receptors, opioids lower the sensitivity of
`medullary chemoreceptors to hypercapnea and blunt respi-
`ratory response to hypoxia.22 This 2-fold effect, reducing
`either respiratory rate or tidal volume, leads to apnea.20 The
`link between acute respiratory distress syndrome (ARDS)
`and opioids has been known since 1880, although the exact
`mechanism is still under dispute.23 The patient will usually
`regain normal ventilation following respiratory depression,
`either spontaneously or after administration of an opioid
`antagonist such as naloxone, and later develop hypoxemia
`and pulmonary edema over the course of the next few minutes
`or hours. Frothy, pink sputum may be present in the patient’s
`
`164
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`© Postgraduate Medicine, Volume 121, Issue 2, March 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
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`airway or in the endotracheal tube of an intubated patient as a
`result of sympathetic discharge.20 Convulsions and premature
`ventricular contractions (PVCs) can also occur as a result of
`hypoxia and subsequent acidemia.21
`Hypotension may also be present because of arteriolar
`and venous dilation caused by histamine release.24,25 Although
`the opioid receptor does not appear to be directly involved
`in histamine release, there may be some nonspecifi c ability
`of opioids to activate mast cell G proteins, which induce
`degranulation of histamine-containing vesicles.26
`Miosis, or pinpoint pupils, is also a sign of opioid overdose.21
`The mechanism remains controversial, with studies showing
`that morphine stimulates parasympathetic pupilloconstrictor
`neurons in the Edinger-Westphal nucleus and increases fi ring
`of pupilloconstrictor neurons to light.27 Oxycodone most likely
`induces miosis via mediation of inhibitory neurotransmission
`resulting in either hyperpolarization of sympathetic nerves or
`removal of inhibition in parasympathetic neurons.20
`Necrosis of intranasal structures, similar to the damage
`associated with chronic cocaine use, has been reported
`as a result of prolonged OxyContin® abuse by snorting
`crushed tablets. The findings included nasal collapse,
`septal perforation, palatal retraction, and pharyngeal wall
`ulceration, which can mimic sinusitis and rhinitis. These
`conditions are most likely a result of a post-infl ammatory
`response to the crushed powder.28
`Unlike normal-release oxycodone, OxyContin® exhibits
`a pharmacokinetic profile with 2 distinct serum peaks,
`allowing for rapid onset and a long duration of action
`(Table 1). Approximately 38% of an orally ingested dose
`is absorbed with a mean half-life of 37 minutes.29 Serum
`concentrations normally peak in approximately 3 hours with
`the oral ingestion of OxyContin®.17 In the case of a large
`oral ingestion, the toxicity may be prolonged secondary to
`slowed gastrointestinal motility and possible pharmaco-
`beazor formation. When OxyContin® is crushed and nasally
`insuffl ated, the controlled-release mechanism is lost, result-
`ing in the rapid rise of serum concentrations. These abuse and
`overdose scenarios ultimately result in altered pharmacoki-
`netic parameters and unpredictable clinical scenarios.
`
`OxyContin® Abuse and Overdose
`
`Differential Diagnosis and Treatment
`Many of the clinical fi ndings in acute opioid overdoses are non-
`specifi c, making diagnosis diffi cult. Hypoglycemia, hypoxia,
`hypothermia, stroke, head injury, and spinal cord injury may
`all mimic OxyContin® poisoning or may exist concomitantly.
`These conditions can be verifi ed by routinely available test-
`ing; however, if present, they do not necessarily exclude an
`OxyContin® overdose. Other overdose symptoms presenting
`similarly may include clonidine, phenylcyclohexylpiperidine
`(PCP), phenothiazines, and benzodiazepines. Each of these
`generally induce unique clues to exclude opioid toxicity,
`such as nystagmus associated with PCP, electrocardiogram
`(ECG) abnormalities with phenothiazines, and coma with
`nearly normal vital signs with benzodiazepines.20 Adding to
`the diffi culty in diagnosis is the low sensitivity and specifi city
`of immunoassay urine drug screens commonly used in the
`ED. The immunoassay drug screen for opiates is specifi c for
`morphine glucuronide and exhibits a 30% cross-reactivity with
`oxycodone. The cross-reactivity can vary between manufactur-
`ers and has been reported to be as low as 5% for some tests.20
`Taking this into consideration, a negative urine drug screen for
`opiates can not necessarily rule out oxycodone ingestion. A
`confi rmatory immunoassay specifi c for oxycodone should be
`ordered if the patient’s clinical picture remains unclear. Many
`OxyContin® overdose patients are simultaneously abusing
`other drugs, making diagnosis even more diffi cult if there is no
`defi nitive confi rmation of the patient’s abuse of the opioid.
`If OxyContin® overdose is suspected, early ventilation
`and oxygenation should be administered, which is generally
`suffi cient to prevent death. However, even in the absence of a
`confi rmation, cautious administration of naloxone—the opiate
`receptor antagonist and antidote for opioid overdoses—may
`have both diagnostic and therapeutic effects.20 Studies have
`shown that high-dose naloxone therapy is safe in patients with
`nonopioid-related conditions, such as spinal cord injury or
`acute ischemic stroke.20,30 Although ventilation assistance may
`still be required because of a delayed response, a small dose
`of 0.05 mg of naloxone administered intravenously typically
`leads to a patient reaction. The goal of this treatment is not
`complete arousal but one of an increased respiratory drive and
`a return to adequate spontaneous ventilation. This approach
`of using a small dose is effective in avoiding endotracheal
`
`Table 1. Pharmacokinetic Profi le of Oxycodone
`Drug Type
`Pharmacokinetic Profi le
`
`Oxycodone Immediate Release (Oral)
`
`Monoexponential
`
`Oxycodone Extended Release (Oral)
`
`Biexponential
`
`Time to Peak
`1.4 ± 0.7 hours
`3.2 ± 2.2 hours
`
`Duration
`
`4–6 hours
`
`8–12 hours
`
`© Postgraduate Medicine, Volume 121, Issue 2, March 2009, ISSN – 0032-5481, e-ISSN – 1941-9260
`
`Half-Life
`
`2–3 hours
`
`4.5 hours
`
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`Aquina et al
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`intubation, enables timely classifi cation of nonopioid causes
`of the patient’s condition, and lowers the risk of acute opioid
`withdrawal.20 High-dose naloxone treatment or subcutaneous
`administration often leads to a faster response but may also
`increase withdrawal symptoms,20 most commonly including
`confusion, restlessness, and headache, and less often aggres-
`siveness, gastrointestinal complaints, tachycardia, shivering,
`seizures, sweating, and tremor.31
`The route of ingestion of oxycodone will infl uence the
`pharmacodynamics on the body. Nasal insuffl ation of oxy-
`codone will result in faster onset and acute toxicity. Small
`bolus doses of naloxone may be effective, as previously
`mentioned. We suggest a bolus of 0.05 to 0.2 mg until a
`desired effect of improving patient hypoventilation. This
`may be determined by hypoxia or elevated CO2 levels. When
`tablets are orally ingested, naloxone and oxygen therapy
`will have to be administered for a longer period of time. In a
`large acute ingestion, toxicity may be delayed and prolonged
`enough to necessitate the use of a naloxone infusion. The
`typical per-hour infusion rate to start with is 2/3 the dose
`required to stimulate the patient. For example, if 3 mg were
`required to maintain the patient’s ventilation status, the subse-
`quent infusion would start at 2 mg/hr. The titration endpoint
`for naloxone infusions is patient respiration.21
`Specific long-term management of OxyContin® abuse
`is treated by several medications. Methadone blocks
`the effects of opioids and if taken regularly prevents
`withdrawal symptoms. It has been used for decades
`to treat people addicted to opioids. Other medications
`include levo-alpha-acetylmethadol (LAAM), an alterna-
`tive to methadone that blocks the effects of opioids for up
`to 72 hours. Naltrexone is a long-acting opioid blocker but
`is not generally used in the acute setting. Other available
`long-term treatments are buprenorphine and suboxone,
`which is a combination of buprenorphine with naloxone.
`Treatment of long-term addiction is not the focus of
`this article; however, management of these patients also
`focuses on psychotherapy along with these medications.
`
`Conclusion
`With the increasing rates of prescription drug abuse,
`OxyContin® overdose will continue to be a challenge
`for physicians to identify and manage. Since the abuse
`is seen in all ages, all health care providers should be
`knowledgeable about this chronic pain agent. Increas-
`ing illegal purchasing and abuse should also prompt
`health care providers to be aware of patients who are
`seeking this drug for recreational use.
`
`Confl ict of Interest Statement
`Christopher T. Aquina BS, Andreia Marques-Baptista, MD,
`Patrick Bridgeman, PharmD, and Mark A. Merlin, DO,
`EMT-P, FACEP disclose no confl icts of interest.
`
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