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Urine Drug Testing -
What Do the Results Mean
and What Do I Tell the
Patient?
Andrea Trescot, MD, FIPP
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Disclosure
Andrea Trescot, MD, FIPP
Pain and Headache Center
Eagle River, AK
President, Alaska Society of Interventional
Pain Physicians
Medical Director: Pinnacle Lab Services
Urine toxicology and genetic testing
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Objectives
In this lecture, we will discuss:
Why do we test?
Who do we test?
When do we test?
How do we test?
What are the ethical issues involving testing?
What do I ask the patient?
What do I tell the patient?
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Actual PatientCurrent Medication List
DURAGESIC 100 mg q3d – days, 10, Ref: 0
METHADONE 10 mg 1 tid – days, 90, Ref: 0
OXYCONTIN 20 mg 1 bid 30 days, 50, Ref: 0
OXYCODONE 5 mg 2-4 tabs qid – days, 196, Ref: 0
OXYCODONE/APAP 10/325 1-2 tabs qid prn, 240, Ref: 0
LORCET 10/500 1 prn, 60 Ref: 0
ALPRAZOLAM 5 mg 1 bid – days, 60, Ref: 0
KLONOPIN 0.5 mg 1 tid – days, 90, Ref: 0
CARISOPRODOL 350 mg 1-2 tabs tid – days, 180, Ref: 0
AMBIEN 10 mg ½-1 hs prn, 30, Ref: 0
BACLOFEN 10 mg 1 tid – days, 90, Ref: 0
LIDODERM 5% 700 mg 1-3 pat – days, 60 Ref: 0
DICYCLOMINE 20 mg 1 qid prn, 30, Ref: 0
POTASSIUM 20 meq 2 qd – days, 60, Ref: 0
AXERT 12.5 mg – days, 12, Ref: 4
FLONASE 2 puffs qhs – days, 1, Ref: 5
Courtesy of: Dr. Manchikanti
UDT: Positive for Cocaine and Marijuana
Negative for ALL Controlled Substances listed above
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Urine Drug Testing in
Clinical Practice
Why do we test?
To evaluate patients
To support assessment & diagnosis
To monitor adherence
To identify use of undisclosed substances
To be a patient advocate
To uncover diversion
Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.
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Urine Drug Testing
To confirm the medicines prescribed are present Depends on timing and absorbsion
To identify the presence of medicines not prescribed Need to understand the metabolism of these
medicines
Toxicology confirmation
No different than following HbA1C for diabetes, LFTs and cholesterol levels for statins, or blood pressure for anti-hypertensives
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Federally Regulated Urine Drug
Testing
Most established use of urine testing
“Federal Five” marijuana (THC) cocaine (benzoylecgonine) opiates phencyclidine (PCP) amphetamine/methamphetamine
Mandated cutoff concentrations too high to be of value in clinical practice
Requirements of federally regulated testing not always applicable to clinical practice
Shults TF. Medical Review Officer Handbook. 8th ed. 2002. Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.
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Drug Detection Test in
Urine
Cutoff Level
(ng/mL)
Morphine 1 to 3 days (2 wks) 300
Methadone 2 to 4 days ( 2 wks) 300
Hydrocodone 2 to 4 days ( 2 wks) 50,000
Oxycodone 2 to 4 days ( 2 wks) 100
Benzodiazepines Up to 30 days 300
Barbiturates (short-acting) 2 to 4 days 300
Barbiturates (long-acting) Up to 30 days 300
Marijuana (chronic use) Up to 30 days 50
Cocaine (benzoylecgonine-cocaine metabolite) 1 to 3 days 300
Amphetamine or methamphetamine 2 to 4 days 1000
Typical Detection Times for Urine Testing of
Common Drugs of Abuse
Note that detection times can vary considerably, depending upon acute versus
chronic use, the particular drug used within a class, individual characteristics
of the patient, and the method used to test for a substance.
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Urine Drug Testing in
Clinical Practice
Who do we test?
New patients already on controlled substances
Any patient for whom you are considering
prescribing controlled substances
Patients who are resistant to full evaluation
Patients who display aberrant behavior
Patients in recovery
Patients who request a specific drug(s)
Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.
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“All of my patients take their
medication as prescribed…”
BMC Health Services: 32% of
patients in primary care practice
committed opioid misuse. Negative for prescribed opioid
Positive for controlled substances not prescribed
Multiple prescribers (doctor shopping)
Diversion of opioids
Prescription forgery
Cocaine and/or amphetamines in urine (40%)
Timothy J. Ives, etal. BMC Health Services Research 2006
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Urine Drug Testing in
Clinical Practice
When do we test?
Considering controlled substances treatment
Making major treatment changes
Support decision to refer
Treatment agreements
Any aberrant drug-related behavior
Third-party reports about aberrant drug-related
behaviors (family, friends, insurers, law enforcement,
etc)
Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.
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Urine Drug Testing in
Clinical Practice How do we test?
Hair
Blood Alcohol blood levels
Saliva No point of service, no metabolites
Urine Easy, less invasive
Point of service is available
Metabolite analysis is available
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Urine Drug Testing - UDS vs UDT
Urine drug screening (UDS)
Point of service (POS) or point of care (POC)
Immunoassay
Rapid, inexpensive
Table top analyzer
Chromotographic
Laboratory
Qualitative (positive or negative), no
metabolites
Multiple drug interactions
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Qualitative Testing
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Initial Drug Test Methods
EIA: Enzyme Immunoassay
KIMS: Kinetic Interaction Microparticulates in Solution
CEDIA: Cloned Enzyme Donor Immunoassay
FPIA : Fluorescence Polarization Immunoassay
RIA: Radioimmunoassay
ELISA: Microplate Enzyme-Linked Immunosorbent
TLC: Thin-Layer Chromatography
Baxter 2003
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Urine drug toxicology (UDT)
Quantitative evaluation
Gas chromatography (GC), or mass
spectrophotometry (MS)
Metabolites
Very accurate
Urine Drug Testing - UDS vs UDT
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Quantitative Testing/Toxicology
“No lower limit” allows for reporting of
results below a standard cut off
“Trough levels”
Evaluated metabolites and potential drug-
drug interactions
Can correlate with patient symptoms
Identifies “pill scraping”
Very expensive
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POC vs GC/LC/MS
Urine toxicology takes time, and POC is instant
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UDT Performance
Manchikanti L et al. Monitoring opioid adherence in chronic pain patients: tool, techniques,
and utility. Pain Physician 2008;11:S155-180
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Interpretation of Urine Testing
Results
Patient has
taken drug
Patient has
not taken
drug
Positive result True positive False positive
Negative
result
False
negativeTrue negative
Wolff K, et al. Addiction. 1999;94:1279-1298.Haddox 2005
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Detection of a particular drug by a drug-class
specific immunoassay depends on
The structural similarity of that drug or its metabolites
to the reference drug
The urine concentration of that drug
The ability of the assay to detect
semisynthetic/synthetic opioids differs among
the various assays
Pitfalls of Urine Drug Screening
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Opiate Screens
Natural
(from opium)
Semisynthetic
(opium-derived)
Synthetic
(man-made)
• codeine
• morphine
• thebaine
• hydrocodone
• oxycodone
• hydromorphone
• oxymorphone
• buprenorphine
• meperidine
• fentanyl
• sufentanil
• propoxyphene
• methadone
Most semisynthetic & synthetic opioids not reliably detected by commonly used screens
Shults TF. Medical Review Officer Handbook. 8th ed. 2002.
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Interpretation of Urine Drug
Testing Results
Requires that you know
How specimen is collected
What is prescribed
Metabolism of drugs
Alternative medical explanations
Scams
Laws, regulations, & guidelines
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Vuilleumier PH, Stamer UM, Landau R. Pharmacogenomic considerations in opioid
analgesia. Pharmgenomics Pers Med. 2012;5:73-87.
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Codeine
Codeine is
metabolized by
CYP2D6 to its
active
metabolite -
Morphine
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Morphine
Morphine is
metabolized by
UGT2B7 to
M6G
(analgesic) and
M3G
(hyperalgic)
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Hydrocodone
CYP2D6 CYP3A4
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Oxycodone
Oxycodone is
metabolized by
CYP2D6 to its
active
metabolite -
oxycodone
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Oxycodone
Oxycodone is
metabolized by
CYP3A4 to its
inactive metabolite -
noroxymorphone
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Tramadol
Tramadol is
metabolized by
CYP2D6 to its
active
metabolite – O-
desmethyl-
tramadol
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Fentanyl
Fentanyl is
metabolized by
CYP3A4 to its
inactive
metabolite -
norfentanyl
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1901
Any recent cough medication?
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Heroin
6-MAM
Heroin
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Methadone is metabolized by
CYP3A4 to the inactive EDDP.
Secondary metabolism by 2B6, 2D6
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Diazepam
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THC -- Marijuana
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THC Testing
Marinol (A synthetic THC) is prescribed for nausea
and weight gain- tests positive
Casamet ( a synthetic cannabinoid) is marketed in
Canada, tests NEGATIVE
Sativex (also Canada) contains THC—will test
positive.
CBD (now available OTC) may or may not contain
THC – depends on the source (marijuana vs hemp)
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Poppy Seeds Causing Morphine?
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UDS Cross Reactions
Manchikanti L et al. Monitoring opioid adherence in chronic pain patients: tool, techniques,
and utility. Pain Physician 2008;11:S155-180
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Additional Methadone False
Positives
Verapamil (Calan®)
Doxylamine (Unisom®)
Cyamemazine (Tercian®)
Alimemazine (Nedeltran®)
Levomepromazine (Nozinan®)
Thiordazine (Mellaril®)
Olanzapine (Zyprexia®)
Lancelin F et al. False positive results in the detection of methadone in urines of
patients treated with psychotropic substances. Clinical Chem 2005;51:2176-
2177
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UDT PCP Cross Reaction
Roche DAT Handbook 1.1
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UDT THC Cross Reaction
Roche DAT Handbook 1.1
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Amphetamine
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Medical Explanations for Positive
Results: Amphetamine/Methamphetamine
Prescription medication
Adderall®
Cross-reaction with structurally similar
prescription drugs for Parkinson’s disease &
OTC diet agents & decongestants
dopamine, isoxsuprine, ephedrine, phenmetrazine,
phentermine, fenfluramine, mephentermine
Drugs metabolized to amphetamine/
methamphetamine
Selegiline (for Parkinson’s), benzphetamine,
dimethylamphetamine, fenproporexShults TF. Medical Review Officer Handbook. 8th ed. 2002.
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Screen and Confirm
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Urine Results Reported as
“None Detected” May mean any of following
Patient Does not use drug
Has not recently used drug
Excretes drug/metabolite faster than normal
“Peak and trough” levels
Urine testing used was not sufficiently sensitive to detect drug at concentration present Ask for “no threshold” testing (GCMS)
Clerical error (wrong sample)
In adherence testing, may raise concerns about misuse/diversion
Wolff K, et al. Addiction. 1999;94:1279-98. Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph].
2004.
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Common Errors of Interpretation
Patient taking hydrocodone
Urine screen for opiates is listed as “morphine”; result reported as positive
Patient accused of not adhering to treatment plan & discharged
GC/MS confirms hydrocodone & hydromorphone
Solution: understand POC testing
Explaination: Some cups label “opiates” as “morphine”
Haddox 2005Added by Jordan
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Common Errors of Interpretation
Patient taking oxycodone
Urine screen for “opiates” reported as
“none detected”
GC/MS not performed
Patient accused of not adhering to
treatment plan & discharged
Solution: order GC/MS
GC/MS=gas chromatography/mass spectrometry
Von Seggern RL, et al. Headache. 2004;44:44-7.
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OXYCODONE
The “Federal Five” screen does NOT include oxycodone
Standard POCT immunoassay will NOT reliably detect oxycodone under the
OPIATE group
Specialized oxycodone immunooassay now available
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Urine Toxicology - Metabolites
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Urine Toxicology
- Stopped Taking Meds
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Methadone and Buprenorphine
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Other Testable Drugs
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Urine Drug Testing in
Clinical Practice
What are the ethical issues involved in urine drug testing?
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Ethical Perspectives
A false-negative or false-positive result
can have a significant impact on a
patient’s access to pain management.
Prescribing physicians should always be
cognizant of the limitations that urine drug
screens present.
The results of these tests should not be used
in isolation to diagnose addiction nor should
they dictate management decisions without
clinical context.
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Ethical Perspectives
The most common scenarios faced when
interpreting urine drug test results are 1) the urine sample is positive for prescribed drugs and
negative for all other prescribed or illicit drugs
2) the urine sample is positive for illicits or non-
prescribed opioids
3) the urine sample is negative for the prescribed
opioids
4) the urine is negative for the prescribed opioids and
positive for ilicits
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Ethical Perspectives
The immense magnitude of the revenue
streams associated with drug screens may
potentially influence prescribing physicians
to routinely incorporate screening into their
practice.
Diagnostic laboratories have benefited
from the growth in urine screens with
revenues purported to have surpassed $2
billion in 2013
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Pain Physicians, and Testing
Labs, Have Been at the Center
of the Increase in Urine Testing
Medicare data demonstrates that the total number of drug tests
reimbursed at physicians’ offices increased from 101 tests
performed in 2000 to over 3.2 million in 2009
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Urine Testing Costs are
Increasing and Threatening
Access
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Fraud Comes at a Steep Price
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Random Testing vs Routine Testing
No evidence to support either
First visit, any unexpected problems, dose
escalation, early refill request, periodic.
Patients at higher risk for abuse might
require more frequent screening.
Screening consistently helps to normalize
the routine nature of providing a specimen.
It makes the request less awkward during an
encounter that is complicated by subversion
and otherwise warrants a UA.
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How Often is Enough but Not
Too Much?
Some specialists recommend 3 random
screens (POC) within the first 12 – 15
months of therapy and once annually
afterwardsOwen GT, Burton AW, Schade CM, Passik S. Urine drug testing:
Current recommendations and best practices. Pain Physician 2012;
15:ES119-E133.
However, that does not assess “pill
scraping” and adulterated urines
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Deception Techniques
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How Often is Enough but Not
Too Much?
Consider intermittent toxicology
Initial assessment
When medications “stop working”
With “red flags”
Medical necessity
How will this change your treatment?
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“My Meds Stopped Working”
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Drug-Drug Interactions
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Diagnostic Dilemmas
Morphine > 6400
Norhydrocodone 36
Hydromorphone 57
Oxycodone >6400
Noroxycodone >6400
Oxymorphone 148
MSER 120mg TID
Oxycodone 30mg q 4 hrs pain score 9/10
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Morphine With Hydromorphone
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Drug Impurities
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Urine Drug Testing in
Clinical Practice
What do we ask the patient?
How well is the medication working? “How long before you notice an an effect?”
“How much relief do you get?” % improvement
“How long does it last?”
This helps to create a “dose/response curve”
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6 12 18 24
analgesia
toxicity
8
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Other Things to Ask…
What is going to be in your urine today?Establishes trust and allows for “on-the-spot” counseling
“Tell me about how you are taking the
medication”
“Tell me about times that you miss or don’t
take the medication”
“Tell me about how you secure the
medication and who has access to it.”
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Urine Drug Testing in
Clinical Practice
What do we tell the patient?
If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids.
If no metabolites, confront the patient (I offer a 30 second “amnesty” – tell me the truth, and there will not be any consequences)
If no active metabolites, consider changing medications
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Diagnostic Dilemmas
Morphine > 6400
Norhydrocodone 36
Hydromorphone 57
Oxycodone >6400
Noroxycodone >6400
Oxymorphone 148
MSER 120mg TID
Oxycodone 30mg q 4 hrs pain score 9/10
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Morphine >64000
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Urine Drug Testing in
Clinical Practice
What do we tell the patient?
If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids.
If no metabolites, confront the patient (I offer a 30 second “amnesty” – tell me the truth, and there will less consequences)
If no active metabolites, consider changing medications
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No Metabolites
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What Do You Do Now?
Discuss why they adulterated the urine.
Consider the risk of continued opioid
prescribing.
Closer monitoring
Consider buprenorphine
Based on the therapeutic relationship, an
alternative to immediate discharge may be
referring the patient to an addiction
specialist.
“A cry for help”
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Urine Drug Testing in
Clinical Practice
What do we tell the patient?
If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids.
If no metabolites, confront the patient (I offer a 30 second “amnesty” – tell me the truth, and there will be less consequences)
If no or low active metabolites, consider changing medications
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Diagnostic Dilemmas
Morphine > 6400
Norhydrocodone 36
Hydromorphone 57
Oxycodone >6400
Noroxycodone >6400
Oxymorphone 148
MSER 120mg TID
Oxycodone 30mg q 4 hrs pain score 9/10
Changed to oxymorphone
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Alcohol Toxicology – A Chance
to Discuss
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Acc VTA
FCXAMYG
VP
ABN
Raphé
LC
GLU
GABA
ENK OPIOID
GABAGABA
GABA
DYN
5HT
5HT
5HT
NE
HIPP
PAG
RETIC
To dorsal horn
END
DA
GLU
Opiates
ICSS
AmphetamineCocaineOpiatesCannabinoidsPhencyclidineKetamine
OpiatesEthanolBarbituratesBenzodiazepinesNicotineCannabinoids
OPIOID
HYPOTHALLAT-TEG
BNST
NE
CRF
OFT
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I would suggest quantitative UDT
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(or UDT)
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Consider addiction referral/discharge
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Continue opioids
Nonopioid treatment
Addictionology referral
Discharge
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Their Conclusion
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Summary:
Before You Order a UDT
Ask patient
Are you taking any prescribed, OTC, or
herbal drugs?
When was last dose? Quantity?
Drug misuse/addiction history
Let laboratory know what you are looking for
Illicit substance
Prescription drug misuse
Presence of prescribed medication
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Summary
Give the patient the benefit of the doubt
Minimize doubt through education and
collaboration, but understand that drug
testing remains an evolving field and there
are several aspects (specific metabolites,
metabolite concentrations, metabolite
ratios, assay limitations, interferences) that
are incompletely understood.
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Summary (continued)
False accusations of abuse or diversion
are unacceptable and may impact the
patients’ ability to receive appropriate
present and future care.
The diseases of abuse and addiction are
chronic and often progressive, and are
rarely (if ever) made on the basis of a
urine drug test.
Place drug testing data in the context of
the total clinical picture.
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Summary - Continued
Finally, have an action plan. What will you
do with the results?
Depending on the situation, this may entail
no special action; close observation;
challenges to change behavior; tightening
of treatment boundaries; consultation with
an addiction medicine specialist; or referral
to a drug treatment center.
Reisfield G. Pitfalls in urine drug test interpretation. The Pain
Practitioner 2009;19(3):16-24
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