DRUG TEST ANALYSIS IN THE PAIN MANAGEMENT PROGRAM J. ELLIOTT BRIGGS, MT, CT(ASCP) FORENSIC TOXICOLOGIST (SAMHSA) TECHNICAL MANAGER PAML TOXICOLOGY

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1 DRUG TEST AALYSIS I THE PAI MAAGEMET PRGRAM J. ELLITT BRIGGS, MT, CT(ASCP) FRESIC TXICLGIST (SAMHSA) TECHICAL MAAGER PAML TXICLGY 1

2 Prescription Drug Abuse: Crisis in America "Drugs have had a devastating impact on American society for more than a century. The human toll of drug abuse- the lost talent And potential of those who have died in drug related incidents-is immeasurable." - Lost Promise Management Triangle Physician Pharmacist Patient 2

3 T MY JB? Management Triangle- ew Member? Physician Pharmacist Patient DEA! Government Problems: DEA In 2005, an estimated 6.4 million Americans age 12 and older reported past month use of prescription drugs for non-medical purposes. f these, 4.7 million used pain relievers non-medically. ationally, the misuse of prescription drugs was second only to marijuana in CY

4 Government Problems: DEA (Cont d) Typically, a traditional independent brick and mortar pharmacy will sell about 180 prescriptions per day. f these sales, only 11 percent will involve controlled substances. Conversely, the typical cyber pharmacy will sell around 450 prescriptions each day 425 of these, or 95 percent, will involve controlled substances Joseph T. Rannazzisi Deputy Assistant Administrator, DEA May 16, 2007 PATIET PRBLEMS VALID 1. Injury 2. ncology (Cancer) 3. Chronic Pain Illicit 1. Diversion (Sales) 2. Hoarding (Singular kick ) 3. Combinations (multiple pharmacies) PRESCRIBED PIIDS A SIGIFICAT SURCE F DRUGS Bought on internet 0.10% Drug dealer/ Stranger 3.90% More than one doctor 1.60% ne Doctor 19.10% Bought/ took from friend or relative 14.80% Free from friend or relative 55.70% ther 4.90% Bought on internet Drug dealer/ Stranger More than one doctor ne Doctor Source: ational Survey on Drug Abuse and Health, 2007 Bought/ took from friend or relative Free from friend or realative 4

5 Source Where Friend/ Relative btained More than one doctor 3.30% Free from friend or relative 7.30% Bought from Friend or relative 4.90% Drug dealer/ Stranger 1.60% ne Doctor 80.70% ther 2.20% More than one doctor Free from friend or relative Bought from Friend or relative Drug dealer/ Stranger ne Doctor ther Source: ational Survey on Drug Abuse and Health, 2007 Physicians Problems: Vulnerability William Hurwitz, M.D., 59 years old, was sentenced to a shockingly harsh term of 25 years in federal prison for a conviction based on his care of pain patients. This is effectively a life sentence and is being appealed. AAPS plans to file an amicus brief in support of his appeal, as will other groups. Dr. Harry Meyer Katz, 79 years old, was convicted in March of 176 felony counts of illegal distribution of controlled substances. He was sentenced to 16 months in prison and fined $75,000. Prosecutors called him Dr. Feelgood for his treatment of pain. Bernard Rottschaefer, M.D., was the latest victim of a disgruntled employee, some patients who were drug addicts, and an overzealous prosecution. Since his conviction on March 9th, six female addicts have sued him claiming that he is the one responsible for their addiction. Physicians Problems (Cont d) 1. Legitimacy of patient pain 2. Redundancy of patient care 3. Dose management 4. Adjunct illicit internet pharmaceutical support. 5. versight by government regulators DEA. 5

6 PAI MAAGEMET 1. ften for treatment of chronic pain, physicians prescribe one of several opioid drugs (e.g. oxycodone, fentanyl, methadone.)- These drugs have a high potential for addiction and abuse. 2. Physicians need to know if the patient is taking the medication as indicated and not diverting (selling), or hording (to make larger doses). 3. Also need to know if the patient is taking nonprescribed drugs during treatment. HW CA THE LAB HELP? Identify the compliant patient. 1. Successfully detect trace amounts of drug during trough stage. 2. Correctly identify metabolic products. 3. Identify esoteric drugs 4. Insure continued acceptance into program. HW CA THE LAB HELP? Identify the clandestine patient 1. Identify un-prescribed drugs 2. Identify patient deception 3. reveal non-compliance. 6

7 LAB SUPPRT FR PAI MAAGMET Lab Testing (specifically urine drug testing) plays an important role in Pain Management. Used to confirm patient compliance with treatment guidelines. Used for risk assessment and patient safety. -Minimize potential for abuse -Minimize potential for diversion -Minimize risks associated with specific drug combinations (e.g. methadone and benzodiazepines- multiple pharmacies.) Challenges in Pain Management Laboratory Support for pain management services can be very problematic Challenges include: - Lack of understanding by clinicians - Lack of assay specificity -An opiate screen does not necessarily contain all desired opiates - Concentration cutoffs for positive results ot the same as Workplace. Challenges in Pain Management Misunderstanding of results or wrong results can lead to discontinuation of treatment for patients with real pain. It is vital for the clinician to have an ongoing dialog with the laboratory and the pharmacy to interpret results. -Educate the physician on the limitations and appropriate testing practices this is not CSI 7

8 WHAT S AVAILABLE? What Works? PCT Kits will not provide necessary sensitivity or selectivity. For Many Labs, the only assay available for support is the opiate immunoassay not specific. -This is problematic does not discriminate between opiate types(will not effectively detect oxycodone.) ot inclusive. -There are some new screen assays for oxycodone, buprenorphine, meperidine, and tramadol but are expensive-may be non-specific. ot legally defensible. The alternative is to use a reference lab for esoteric testing. How Does Pain Management Testing Compare with Workplace Drug Testing? Lower cut off for pain meds (negative result is a red flag). Expanded panel of included drugs (fentanyl, buprenorphine, oxycodone, oxymorphone, etc) Quantitative results results should be relative to patient dosage. Specific Drug Directed. Concerns in the Pain Management Drug Screen - Collection/ Analysis 1. Verification of use 2. Validity of Test 3. Identification of Drug 4. Interpretation of Test 5. Selection of Correct Test 6. Sensitivity of Test V 2 I 2 S 2 8

9 VERIFICATI F USE: Collection Timing! 1. Insure that the collection is not expected; patient WILL anticipate. 2. Collection environment MAY foster cheating observed collection? 3. Attempt peak rather than trough timing. (Patient should be in a steady state mode, so may not be important.) 4. Collection on Monday morning will identify illicit weekend use. VALIDITY F TEST 1. Many drugs will not be identified on a routine drugs of abuse test. (Meperidine, fentanyl, buprenorphine, oxycodone, carisoprodol, cyclobenzeprine.) Many labs fail to provide specific, sensitive, tests to identify drugs present (often a GC/MS or LC/MS/MS is required too expensive for most labs.) Quality of the lab should be verified. Are they certified with a reputable agency? CAP-FUDT, SAMHSA? IDETIFICATI F DRUG: Are you looking for the right analyte? 1. When using urine testing, remember that you are looking for the metabolite of the drug. Absence of the metabolite identifies a nonmetabolizer (patient is not benefiting from the drug) R an illicitly spiked sample. Does the Lab Look for the Metabolite? - Codeine metabolizes to morphine - Hydrocodone metabolizes to hydromorphone. - xycodone metabolizes to oxymorphone. - Fentanyl metabolizes to nor-fentanyl 9

10 EW DEVELPMETS: piate Metabolism Codeine Heroin H H H 3C H H 3C Minor Hydrocodone 5-13% 100% H H 3C Morphine H 6-Monoacetylmorphine 100% H H H H PIATE METABLISM Hydrocodone H xycodone H H 3C Morphine H 3 C H 5% H H 13-14% Minor Hydromorphone H xymorphone H H H Managing The Pain Management Patient: ot All That Easy Avoid the Easy Answer 10

11 3 Patients prescribed Avinza, Urine testing Performed Patient #1- Morphine , Hydromorphone 70 ng/ml. Patient #2- Morphine 6000, Hydromorphone 450, Hydrocodone 600 ng/ml Patient #3 Morphine ng/ml. Who is compliant? 1. Patient #3 nly 2. Patient #1 and #3 3. one are compliant. Patient #1 and #3 Selection of the Correct Test: Is this a clinical or a forensic test? 1. Discuss your needs with the laboratory. 2. Be sure that they can accurately identify the patient s drug use. 3. The laboratory should have a menu of Drug Panels that will suit your needs. Patient is receiving Vicodin for pain. Which is the expected lab report? A. Hydrocodone 5,000 ng/ml. B. Hydrocodone 2,800 ng/ml, hydromorphone 800 ng/ml C. Hydrocodone 5,000 ng/ml, Hydromorphone 500 ng/ml, oxymorphone 75 ng/ml. D. B and C B The parent and metabolite 11

12 Interpretation of the Test Results Certifying Scientist Review Certifying Scientist Review 1. Review of Initial Analysis Data SVT testing. 2. Verification of Equipment Function 3. Review of Mass Spectrometer Data 4. Review of all controls. 5. Review of Chain of Custody 6. Sole accountability for Report 7. Expert Reference for Interpretation Sensitivity and accuracy of the Analysis Important that the laboratory CA identify the drug at the low nanogram level to avoid dropping the critical need patient from the program. ften only possible with expensive mass spectrometer equipment (e.g fentanyl, buprenorphine.) 12

13 Case History #3 A patient is tested to verify morphine use. A workplace drug test is ordered with the following result: Screen negative for drugs of abuse. Creatinine level is 18 ng/ml, specific gravity is ph is 6.8. o adulterants were found Should this patient be eliminated from the program?! Case Study #4: The Patient is being prescribed xycontin for chronic back pain. A drug screen is ordered and the opiates came back negative. A. The physician should review what the test included. B. The physician should look to see what the creatinine level was. C. The patient is non-compliant. D. A and B. D. A and B Compliance Testing: LD DRUG RDER CDE LD Buprenorphine CPBUP 2.5 ng/ml Codeine CPP6 75 ng/ml Fentanyl FETU 1.0 ng/ml Hydrocodone CPP6 75 ng/ml Hydromorphone CPP6 75 ng/ml Methadone CPMETD 90 ng/ml Morphine CPP6 75 ng/ml xycodone CPP6 75 ng/ml xymorphone CPP6 75 ng/ml Propoxyphene CPPRP 45 ng/ml 13

14 ew Developments on the Horizon!! ew World Approach to Medicine Answers the Question: Why do people respond to drugs as they do? Identifies the drug response BEFRE the dose. Pharmacogenomics Identify how the individual will respond to the medication. How? Identification of Single-nucleotide polymorphisms (SP s) Genetic identification of expected immune response. 14

15 Single ucleotide Polymorphisms Definition: A condition where the ucleotide sequence at one Specific location is changed, inserted, or deleted. Lets Look At The Past! Individual Succumbs to Disease Treat the symptoms!!!!! Revolutionary Idea!!! Let s Immunize the Individual so that they don t get the disease in the first place. Why Bother? Between 1997 and 2001 thirteen drugs were removed from the market due to adverse reactions in SME MEMBERS F THE PPULATI Adverse drug response is the fourth leading cause of mortality in the United States. 15

16 Why Is Genetics Important? 1. Many drugs/ substances are handled differently by different people. (Ethanol in Indians, codeine in some people.) 2. ften ethnically associated. 3. Prime area of interest is in polymorphism in the Cytochrome 450 2D6 system of the body. 4. CYP2D6 is a drug metabolizing enzyme whose activity affects the metabolism of one in five commonly prescribed drugs. Drug Metabolizing Enzymes with Genetic Polymorphism Enzyme Representative Therapeutic Substrates Cytochrome P4502D6 -acetyltransferase Cytochrome P4501A2 Cytochrome P4502C19 Cytochrome 4502C9 UDP-glucuronosyl transferase Dihydroprimidine dehydrogenase Desipramine Procainamide Theophyline meprazole Phenytoin Irinotecan 5-Flouroucil Example -Herceptin: A personalized Cancer Drug 1. Human epidermal growth factor receptor 2 gene (HER-2) 2. HER-2 protein is overexpressed in 25-30% of women positive for breast cancer. 3. This protein appears to enhance cell growth and division strongly contributing to tumor progression 16

17 Herceptin 1. Binds to protein produced by HER-2 gene 2. Significantly reduces the metastatic action of the cancer.. 3. Via immunoassay, the clinician can determine IF the patient has HER-2 gene expression AD IF the treatment with Herceptin is warranted. Drugs Metabolized by CYP2D6 Beta Blockers Antiarrhythmics Tricyclic Antidepressants eroleptics ther Drugs Bufuralol Amiodarone Amitriptyline Perphenazine Amifamine Metaprolol Encainide Clomipramine Thioridazine Codeine Propranolol Flecanide Desipramine Debrisquine Timolol Mexilitine Imipramine Detromethorphan - propylamaline Propafenone ortrityline Ethylmorphine Guanoxan Sparteine 4-Hydroxyamphetamine Indoramin Methoxyohenamine Phenformin Final ote The Best Interpretation is born from documented history And medical knowledge of the Patient + = 17

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