OPIOIDS Testing and Interpretation
TOPICS OF DISCUSSION Effects of Opioids Opiates vs. Opioids Drug Testing Recent Trends OPIOIDS: Testing and Interpretation 2018 2
EFFECTS OF OPIOIDS 3
Opioid Receptors µ (mu) receptor: produce central depression analgesia, respiratory depression, miosis, euphoria, reduced gastrointestinal motility, hypothermia, bradycardia, physical tolerance and dependence Κ (kappa) receptor: produce spinal analgesia, sedation, miosis, diuresis, mild respiratory depression and low addiction liability δ (delta) receptor: spinal analgesia, dysphoria, delusions, hallucinations, and respiratory and vasomotor stimulation OPIODS: Testing and Interpretation 2018 4
AGONIST AND ANTAGONIST Opioids are classified into three groups Full agonist : compounds that have an affinity for opioid receptors of a certain type Mixed agonist-antagonist: compounds with an agonistic effect at one class of receptor and an antagonistic effect at another Full antagonist: compounds that inhibit agonist binding of other compounds; have reduced analgesic effect and are primarily used for the treatment of opioid intoxication 5
EFFECTS Nervous Euphoria Analgesia Sedation Mental clouding and mood swings Pulmonary Respiratory Depression Decreased Responsiveness Gastrointestinal Nausea Vomiting Constipation Other Cough suppression Miosis Truncal rigidity Flushing and warming of the skin Sweating and itching OPIOIDS: Testing and Interpretation 2018 6
EFFECTS Human Performance Driving Slow driving Weaving Poor vehicle control Poor coordination Slow response to stimuli Delayed reactions Difficulty following instructions Falling asleep at the wheel OPIOIDS: Testing and Interpretation 2018 7
WARNING www.drugrehab.com 8
OPIATES VS. OPIOIDS Classification 9
DEFINITIONS Opiates alkaloids derived directly from the poppy plant Opioids broader class of drugs that are capable of either producing opium like effects or binding to opioid receptors Semisynthetic opioids created by the chemical modification of an opiate Synthetic opioids a chemical compounds not derived from an opiate, that are capable of binding to an opioid receptor and producing opioid effects clinically 10
OPIATES ALKALOIDS DERIVED DIRECTLY FROM THE POPPY PLANT Opium Morphine, Codeine, Thebaine, Papaverine, Noscapine, Oripavine Morphine Extracted from opium, 1806 Named after Morpheus, the god of dreams Strong µ agonist, weak δ and κ agonist Analgesic Potency = 1 Anesthetic supplement, injuries, musculoskeletal, pain management Schedule II/III 11
OPIATES ALKALOIDS DERIVED DIRECTLY FROM THE POPPY PLANT Codeine Extracted from opium, also derived from methylation of morphine Weak µ agonist, weak δ agonist Analgesic Potency = 0.1 Injuries, musculoskeletal, cough Schedule II/III Analgesic Potency 1.2 1 0.8 0.6 0.4 0.2 Analgesic Potency of Opiates/Opioids 0 Morphine Codeine 12
SEMISYNTHETIC OPIOIDS Hydrocodone Derived from Codeine µ agonist Analgesic Potency = 1-2 Injuries, musculoskeletal, pain management, cough Schedule II Hydromorphone Derived from Morphine Strong µ agonist Analgesic Potency = 7-10 Injuries, musculoskeletal, pain management Schedule II Analgesic Potency 9 8 7 6 5 4 3 2 1 0 Analgesic Potency of Opiates/Opioids 13
SEMISYNTHETIC OPIOIDS Oxycodone Derived from Thebaine µ agonist Analgesic Potency = 1-2 Injuries, musculoskeletal, pain management Schedule II Oxymorphone Derived from Thebaine Strong µ agonist Analgesic Potency = 8-15 Injuries, musculoskeletal, pain management Schedule II Analgesic Potency 12 10 8 6 4 2 0 Analgesic Potency of Opiates/Opioids 14
SEMISYNTHETIC OPIOIDS Heroin Derived from Morphine, 1874 Sold as a pharmaceutical until abuse became rampant Strong µ agonist Analgesic Potency = 4-5 6-AM metabolite is 4 times more potent than morphine Schedule I https://www.deamuseum.org/ccp/opium/history.html 15
SEMISYNTHETIC OPIOIDS Buprenorphine Derived from Thebaine Parital µ agonist, κ agonist High affinity to receptors producing longer-lasting morphine-like analgesia Analgesic Potency = 40 Detoxification and maintenance in heroin dependence, pain management Schedule III https://www.confirmbiosciences.com/knowledge/drug-facts/buprenorphine/ 16
ABSTINENCE SYNDROME 8-12 hours Watery eyes Yawning Mucus fills nasal cavity Perspiration 12-24 hours Irritability Goose flesh Restless sleep Weakness Pupil dilation Tremors Loss of appetite Muscle twitching 17
ABSTINENCE SYNDROME 48-72 hours Increased irritability Increased heart rate Insomnia Hypertension Loss of Appetite Hot and cold flashes Sneezing Alternating sweating and flushing Nausea and vomiting Piloerection Body temperature increases Rapid breathing Abdominal cramps Aching muscles Syndrome duration 7-10 days 18
SEMISYNTHETIC OPIOIDS Naloxone Derived from Oxymorphone Strong µ antagonist Reverse the effects of opioids, overdose treatment Not scheduled Naltrexone Derived from Oxymorphone Strong µ antagonist Reverse the effects of opioids, overdose treatment Not scheduled www.narcan.com 19
ANTAGONIST Stronger affinity to the opioid receptors Lasts for 30-90 minutes Allowing person to breathe again and reverse overdose https://www.northcarolinahealthnews.org/2017/07/12/naloxone-101-works-using/ 20
SYNTHETIC OPIOIDS Fentanyl Strong µ agonist Analgesic Potency = 100-200 Pre-/postoperative, anesthetic supplement, pain management Schedule II Methadone Strong µ agonist Analgesic Potency = 1 Detoxification, maintenance, pain management Schedule II Meperidine Strong µ agonist Analgesic Potency = 0.1 Injuries, postoperative pain, obstetrics Schedule II Propoxyphene µ agonist Analgesic Potency = <0.1 Schedule IV No longer sold in US, 2011 21
SYNTHETIC OPIOIDS Tramadol µ agonist Analgesic Potency = 0.1-0.2 Injuries, musculoskeletal, pain management Schedule IV Others Diphenoxylate treat diarrhea LAAM (levacetylmethadol) treat opiate addiction Loperamide treat diarrhea Tapentadol treat moderate to severe pain 22
DRUG TESTING OPIATES and OPIOIDS OPIOIDS: Testing and Interpretation 2018 23
PREFERRED MATRICES 24
URINE Detection time is 24-72 hours Pros Ability to split the sample for additional testing Industry standard Broad cost effective menu Cons Requires visually observed collection to avoid adulteration/substitution Potential for specimen dilution/adulteration in vivo and in vitro OPIOIDS: Testing and Interpretation 2018 25
ORAL FLUID Detection time is 12-36 hours Pros Samples may be collected in the field and does not require same gender collection. If collected correctly, it is difficult to adulterate Is recommended for clients that may be on certain medications or for medical reasons (Dialysis/catheter) Cons Short detection period Ineffective for THC Detection Moderate cost OPIOIDS: Testing and Interpretation 2018 26
HAIR FOLLICLE Detection time for head hair: 14-90 days prior Detection time for body hair: 30-365 days prior Pros Effective baseline test Unknown drug use history Adulteration difficult Cons Not useful for routine monitoring Limited test menu Head hair may not be available May not pick up a single drug use OPIOIDS: Testing and Interpretation 2018 27
DETECTION PERIODS Media Urine Oral Fluid Hair Approximate Detection Period 24-72 hours 12-36 hours Head hair: 14-90 days prior Body hair: 30-365 days prior OPIOIDS: Testing and Interpretation 2018 28
INITIAL SCREENING TESTS Immunoassay Point of Care Testing (POCT) Lab Based Fast Minimal sample prep False positives 29
OPIATES/OPIOIDS IN URINE Looking for: Codeine/Morphine/Hydrocodone/ Hydromorphone Oxycodone/Oxymorphone Heroin Methadone Buprenorphine Fentanyl Test for: Opiates Oxycodone Heroin (in conjunction with Opiate test) Methadone Buprenorphine Fentanyl 30
CONFIRMATION TESTING GC/MS LC/MS/MS Positive identification Quantitation Sample preparation required www.agilent.com 31
GC/MS RESULTS Morphine Codeine Oxymorphone Hydromorphone 6-MAM Oxycodone Hydrocodone 32
GCMS INTERPRETATION Drug Opiate Parent Drug/Metabolite Heroin Diacetylmorphine 6-MAM, Morphine, Codeine Tylenol #3, #4 Codeine Codeine, Morphine MS Contin, Roxanol Morphine Morphine, Hydromorphone Vicodin, Vicoprofen, Tussionex, H-C Tussive Hydrocodone Hydrocodone, Hydromorphone Dilaudid Hydromorphone Hydromorphone Oxycontin, Percodan, Percoset, Roxicet Oxycodone Oxycodone, Oxymorphone Opana Oxymorphone Oxymorphone OPIOIDS: Testing and Interpretation 2018 33
CASE #1 34
CASE #2 35
CASE #3 36
CASE #4 GCMS 6-MAM Negative 10 NG/ML GCMS URINE 37
EXAMINING THE EXCUSES - OPIATES I am positive for opiates because of my methadone. Synthetic Opioids will not test positive on the standard opiate screening test. Methadone Buprenorphine Tramadol Fentanyl Meperidine I tested positive because I ate a poppy seed bagel. Possible morphine in or on the seeds Problematic at the 300 ng/ml cutoff OPIOIDS: Testing and Interpretation 2018 38
CUTOFF LEVELS/COMPARING RESULTS Regulated standards observed by SAMHSA, CLIA, CAP Set to eliminate positive results due to incidental exposure Reports will indicate cutoff levels for screening and confirmation testing Results from different samples collected the same day may not correlate. Hair vs. Urine Oral Fluid vs. Urine OPIOIDS: Testing and Interpretation 2018 39
RECENT TRENDS OPIOIDS: Testing and Interpretation 2018 40
Embedded PowerPoint Video 42
LOPERAMIDE Imodium µ agonist in the myenteric plexus of the large intestine Excessive dosing (10+ times higher than recommended) At high concentrations loperamide can cross the blood-brain barrier Attempt to get high Treat opioid withdrawal symptoms Can fatally disrupt the heart s rhythm Insufflation may be attempted 42
FENTANYL Uses Pain 50-100 times more potent than morphine Actiq, Duragesic, Sublimaze Abuse Street names: China Girl, China White, Tango and Cash Patches Remove the gel and take the entire 3-day dose at one time Wear multiple patches 43
DEADLY SYNTHETIC OPIOIDS U-47700 PINK 8 times more potent than morphine Sold as a research chemical (China) No approved medical use Not approved for human consumption FDA DEA Schedule I ban November 2016 46 confirmed fatalities between October 2015-September 2016 Image from www.nydailynews.com 44
DEADLY SYNTHETIC OPIOIDS Non-Pharmaceutical Fentanyl Carfentanil (Wildnil) Schedule II 10,000 times more potent than morphine Intended for large-animal use DEA Issues public warning in September 2016 2 mg could be lethal Powder, blotter paper, tablets, spray Can be absorbed through skin or inhaled 45
DEADLY SYNTHETIC OPIOIDS Sufentanil 500-1000 times more potent than morphine Furanyl Fentanil 20 times more potent than morphine Acetylfentanyl 15 times more potent than morphine Many others with varying degrees of potency 46
KRATOM Mitragynine Extract from tropical tree Mitragyna speciosa, native to Southeast Asia Currently not scheduled At low doses produces stimulant effect Increased energy, sociability, alertness At high doses produces opioid effect Sedation, pleasure, decreased pain Image from www.kratomspot.com 47
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