Cooking Meth and Doctor Shopping: The Challenges of Managing Prescription Therapeutics

Transcription

1 Cooking Meth and Doctor Shopping: The Challenges of Managing Prescription Therapeutics James H. Nichols, PhD, DABCC, FACB Professor of Pathology, Microbiology, and Immunology Medical Director, Clinical Chemistry Associate Medical Director of Clinical Operations Vanderbilt University School of Medicine Nashville, TN

2 Objectives Describe clinical cutoffs for screening and confirmation of DAU tests Identify methods patients use to fool drug testing Respond to common clinical questions regarding DAU test results

3 Case Physician calls regarding interpretation of DAU test results. Patient is on OxyIR (oxycodone intermediate release), #180/mo. Drug test results: opiate screen positive (>30,000 ng/ml reactivity), confirmed as morphine (50,000 ng/ml) and hydromorphone (120 ng/ml).

4 Audience Poll What interpretation should be given for the results of morphine and hydromorphone detected in a patient prescribed OxyIR? A. Consistent with OxyIR ingestion B. More consistent with hydromorphone ingestion C. More consistent with morphine ingestion alone D. Consistent with morphine and hydromorphone ingestion

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6 Laboratory Interpretation On review of results, screening immunoassay was positive (>30,000 ng/ml reactivity) to opiate class and negative for oxycodone reactivity. Confirmation by GC/MS demonstrated the presence of morphine (50,000 ng/ml) and hydromorphone (120 ng/ml). These results are more consistent with the use of morphine than oxycodone, as trace amounts of hydromorphone can be seen with higher concentrations of morphine. Please contact lab if further questions.

7 Discouraging Doctor Shopping

8 Urine Drug Testing Cutoffs (ng/ml) Initial Confirm Marijuana Cocaine Opiate Phencyclidine Amphetamines 500 Amp 250 Methamp 250 MDMA 250

9 Drug Detection Detection depends on: Amount ingested Single or chronic abuse Time since last dose Elimination kinetics renal/liver function Hydration status

10 Screen then Confirm screen large numbers of samples quickly and at low cost expect most samples to be negative include ALL positives exclude maximum number of false positives appropriate sensitivity robust to sample adulteration confirmation is slower and more expensive highly specific for individual compounds quantitative, reported qualitatively result amenable to peer review GCMS is method of choice (mandated by SAMHSA) identification based on retention time and fragmentation pattern

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12 The Anti Drug Testing Market Diuretics seeks to dilute the sample physiologically by producing more urine Additives attempt to block the initial screening test Substitution submission of another s urine or a urine substitute

13 Diuretics Urine Luck Pre Tox Capsules * Take all six Pre-Tox capsules hours before deadline with 16 oz. of water * Wait 15 minutes and consume another 16 oz. of water * After taking the capsules, individuals should be prepared to urinate frequently * Ingredients: Dandelion Root, Red Clover, Celery Seed, Chamomile, Sarsaparilla, Uva Ursa, Alfalfa, St. John Wort, Creatine

14 Lower Urine Drug Concentration Excessive water intake Diuretics especially loop these are banned substances in athletics testing programs Luceri et al., JAT 1997;21:244-5 Took 100 samples negative for DOA with low creatinine (range g/l) Concentrated under stream of N2 till creatinine in range g/l) Repeat DOA testing showed 27 positives: 14 morphine 1 cocaine 5 THC 2 amphetamines 5 benzodiazepines

15 Sample Substitution

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19 Adulterants 19

20 Adulteration Prevention Observed collection Test every urine for additives salt, water content, creatinine (natural metabolite) Measure temperature substitution Measure for specific contaminants acids, bases (ph), nitrites, pyridine, bleach, glutaraldehyde, soap.

21 Urine Adulteration Test Kit creatinine (dilution) nitrite (Klear, Whizzies) glutaraldehyde (UrinAid, Clear Choice) ph (vinegar, bleach, Amber-13) SG (dilution) Drug Detection Devices Ltd Oxidizing agents (bleach) pyridinium chlorochromate (Urine Luck) 21

22 Case 47 y/o female, Hx Wegener granulomatosis and vasculitis, extensive surgery resection of frontal nasal sinus cavity and septum. Receiving aggressive opiod pain management. Policy to randomly test all pain management patients 3 4x/yr for compliance and to exclude illicit abuse. On 10/31 patient tested positive for cocaine by FPIA. Denied abuse in past few months, claimed passive exposure to cocaine smoke from her upstairs apartment neighbor, a crack addict. Submitted second urine on 11/2, also positive. At this time patient claimed she uses an herbal medication, mugwort and produced some for the physician.

23 Audience Poll How can the laboratory assist the physician? A. Send the clinician the package insert which indicates mugwort has not been tested B. Believe the patient, as some herbal products can cross react with immunoassay screening tests C. Test a tea brewed from the patient s mugwort to determine if it is responsible for the positive result D. Compare the patient s mugwort with a sample of real mugwort obtained from an herbal shop

24 Clin Chem 2002; 48:958-9.

25 Audience Poll Clinician indicates that a patient proclaims her drug test is positive for THC due to marijuana smoke exposure, being in room with a smoker. What is your response? A. Yes, that could cause positive result, suggest the patient stay away from pot smoke B. Not possible, this is an old wives tale C. While it is possible to absorb trace amounts of THC from passive smoke, this will not be sufficient to generate a positive result D. Only passive smoke from methamphetamine could trigger a positive result in the patient (for amphetemines), THC needs a higher concentration

26 Passive Marijuana Very unlikely a person can inhale enough marijuana smoke to have a positive urine test. Perez Reyes (1983) 3 experiments automobile and 2 in small room. Only 2 samples triggered EMIT positive with 20 ng/ml cutoff, one sample by GC/MS gave only 3.9 ng/ml. Law study in room (10x20x8 ft) 4 non smokers played cards over 3 hrs while 6 other males smoked, none of the samples exceeded 7 ng/ml Morland study, car with hashish and marijuana, none of the passive inhalers showed detectable levels, smoker levels ranged ng/ml Cone double blind studies with extreme exposure (subjects wore goggles to protect eyes) maximum urine GC/MS was 12 ng/ml. Mule study of 8 smokers and 3 nonsmokers in 10x10x8 ft room, no windows. Urines of passive smokers were consistently <10 ng/ml So improbable that non smokers could passively absorb enough THC to trigger a positive against SAMSHA cutoffs of 50 ng/ml screen with 15 ng/ml confirm. USDTL website 12/2014 references at end of presentation

27 Case 31 y/o male, Hx bipolar disorder and illicit drug and alcohol abuse. Clean for 3 mos. Found at home, naked, confused, and wandering around back yard. On presentation to ED, diaphoretic, confused, hallucinating, mydriasis, jerking movements of hands and feet, poor gag reflex and increased salivation. Differential considered seizure and drug intoxication. Probable Hx of recent mushroom ingestion. After patient stabilization, with sedation and intubation, a plastic bag containing 1.2 lbs dried mushroom found in patient s possession, labeled Washington Aminita muscaria.

28 Case Picture of Mushrooms

29 Audience Poll The clinicians would like to test for mushroom intoxication, what should the lab do? A. Run a full MS scan for mushroom toxins B. Analyze for psilocybin offered by reference lab C. Offer to send the sample to state lab for testing D. Indicate clinicians must treat symptomatically as no specific tests available

30 Summary The toxicology lab cannot test for everything. Drug testing is not fool proof, and there can be both false positives and false negative test results depends on concentration of analyte in sample Conscious patients may have motive to fool their testing and patients may not be truthful about Hx Laboratory interpretations should be based on fact, what is detected, not why or how that drug is in the sample, as the lab doesn t know the patient.

31 Review Questions A patient with Hx of illicit drug use on adderall for ADHD is positive for methamp (3500 ng/ml) and amphetamine (5500 ng/ml), what is the most appropriate interpretation of these results? A Adderall can cause both methamphetamine and amphetamine to be positive B Adderall will cause positive methamphetamine but not amphetamine C Adderall will cause positive amphetamine but not methamphetamine D Adderall will not cause either methamphetamine or amphetamine to be positive A patient is being prescribed morphine and OxyIR with a positive drug test for morphine (48,000 ng/ml), hydrocodone (5,000 ng/ml), hydromorphone (6,500 ng/ml), oxycodone (6,900 ng/ml), and oxymorphone (6,400 ng/ml). What is the most appropriate interpretation of these results? A Consistent with ingestion of morphine and OxyIR. B Consistent with ingestion of morphine and Oxy IR, but also shows presence of hydrocodone C Consistent with ingestion of OxyIR, but also indicates heroin use D Consistent with ingestion of morphine, but not OxyIR A patient is being prescribed morphine and OxyIR with a positive drug test for morphine (127,000 ng/ml), oxycodone (760 ng/ml) and oxymorphone (1,170 ng/ml). What is the most appropriate interpretation of these results? A Consistent with ingestion of morphine and OxyIR B Consistent with ingestion of morphine, but not OxyIR C Consistent with ingestion of OxyIR, but not morphine D Consistent with ingestion of morphine and OxyIR, but also numorphan (oxymorphone)

32 References A.P. Mason, M. Perez Reyes, A.J. McBay, and R.L. Foltz.Cannabinoid concentrations in plasma after passive inhalation of marijuana smoke. J. Anal. Toxicol. 7: (1983) M. Perez Reyes, S. DiGuiseppi, and K.H. Davis. Passive inhalation of marijuana smoke and urinary excretion of cannabinoids. J. Am. Med. Assoc. 249: 475 (1983) M. Perez Reyes, S. DiGuiseppi, A.P. Mason, and K.H. Davis. Passive inhalation of marijuana smoke and urinary excretion of cannabinoids. Clin. Pharmacol. Ther. 34: (1983) B. Law, P.A. Mason, A.C. Moffat, L.J. King, and V. Marks. Passive inhalation of cannabis smoke. J.Pharm. Pharmacol. 36: (1984) J. Morland, A. Bugge, B. Skuterud, A. Steen, G.H. Wethe, and T. Kjeldsen. Cannabinoids in blood and urine after passive inhalation of cannabis smoke. J. Forensic Sci. 30: (1985) E.J. Cone and R.E. Johnson. Contact highs and urinary cannabinoid excretion after passive exposure to marijuana smoke. Clin. Pharmacol. Ther. 40: (1986) E.J. Cone, R.E. Johnson, W.D. Darwin, D. Yousefnajad, L.D. Mell, B.D. Paul, and J. Mitchell. Passive inhalation of marijuana smoke; urinalysis and room air levels of delta 9 tetrahydrocannabinol. J. Anal. Toxicol. 11: (1987) E.J. Cone. Marijuana effects and urinalysis after passive inhalation and oral ingestion. In Research Finding on Smoking of Abused Substances.C.N. Chiang and R.L. Hawks, Eds. Natl. Inst. Drug Abuse Rs. Monogr. Ser 99: (1990) S.J. Mule, P. Lomax, and S.J. Gross. Active and realistic passive marijuana exposure tested by three immunoassays and GC/MS in urine. J. Anal. Toxicol. 12: (1988) Journal of Analytical Toxicology, Vol. 19, October 1995 pp