W12 - Opioids Notes.pdf

‘I’m 72 years old, a grandmother of five and a great-grandmother too, living alone since my husband passed away five years ago. Since my spinal stenosis surgery a year and a half ago, life is a nightmare. I have to say that OxyContin saved my life, even though I call it a “fake” life. I can do the l...

‘I’m 72 years old, a grandmother of five and a great-grandmother too, living alone since my husband passed away five years ago. Since my spinal stenosis surgery a year and a half ago, life is a nightmare. I have to say that OxyContin saved my life, even though I call it a “fake” life. I can do the little things sure, like doing the dishes, straightening up the house for a while, without letting people know that I’m crying inside. But the fact is that I’m 90 percent disabled and miserable all the time. I know it could be worse; if it was, I think I would end it all tomorrow. So please don’t take away my medicine. It’s keeping me around. Maybe I’m addicted, I don’t know. Maybe if the doctor took away my OxyContin, I would try to get it any way I could. I’d probably be out there with those people who hold up those drugstores.’ www.soberliving.com/blog. OPIOIDS PSY3142 HISTORY • Opium cultivated (6th millennium B.C.E) • Increase in British opium consumption (19th cent.) • Morphine (mid-1800s) • Heroin • Invented in 1898, modified morphine • US ban 1924 AGENDA • Source and use • Use • Pharmacology • Effects • Treatment 4 SOURCE AND USE 5 ORIGINS AND SOURCES OF OPIOIDS • Poppy (papaver somniferum) • Opium • Morphine (10%) • Codeine (.5%) • Thebaine (<.5%) LARGE GROUP OF DRUGS Opiates: Opium: morphine, codeine, thebaine Opiate Derivatives: heroin, hydromorphone (Dilaudid), oxymorphone (Numorphan), oxycodone (Percodan, Percocet, or the longer lasting oxycontin), hydrocondone (Vicodin, Hycodan) Synthetic opiates: methadone, meperidine (Demerol), propoxyphene (Darvocet), LAAM (Orlaam), tramadol (ultracet), buprenorphine (subutex), Fentanyl (Sublimaze), carfentanyl (Wildnil – lg animal tranq) 7 GLOBAL TRENDS 2021 8 November 13, 2021DOI:https://doi.org/10.1016/j.eclinm.2021.101198 SELF-REPORTED MEDICAL USE OF OPIOID PAIN RELIVER USE IN CANADA 9 SELF-REPORTED PAST YEAR NON -MEDICAL USE OF OPIOIDS IN CANDA 2019 DATA • 1% of Canadians 15+ used opioids for nonmedical purposes in the past year • The 2018–2019 Canadian Student Tobacco, Alcohol and Drug Survey (CSTADS) found that 1.8% of students in grades 7 to 9 in Canada (up from 1.2% in 2016–2017) and 4.7% of students in grades 10 to 12 (unchanged from 2016–2017) reported past-year use for medical purposes 10 • The 2019-2020 Canadian Postsecondary Alcohol and Drug Use Survey shows that 22.5% of students surveyed reported using pain relievers nonmedically Opioid Toxicity Deaths in Canada 11 PSYCHOPHARMACOLOGY PSYCHOPHARMACOLOGY 12 ROUTES OF ADMINISTRATION • Generally, opiate drugs are water soluble • Some are more fat soluble • These characteristics can impact which route works best Oral Intranasal Inhalation Parenteral (e.g. subcutaneous, IV) Table 11.1 Opioid Drug Formulations and Routes of Administration Opioid Drug Routes of Administration for Pharmaceutical Formulations Morphine Oral (tablet, capsule); Rectal (suppository); Injected, swallowed, smoked Parenteral (i.v., i.m., s.c. injectable solution) Heroin Parenteral (i.v., i.m., s.c.)* Injected, snorted, smoked Codeine Oral (tablet, capsule, syrup); Parenteral (i.m., s.c. injectable solution) Injected, swallowed (often mixed with soda or flavorings) Hydrocodone Oral (tablet, capsule, syrup) Injected, swallowed, snorted Common Recreational Routes of Administration DISTRIBUTION • Most opiates are slow in crossing Blood-Brain Barrier, but easily cross the placental barrier • Heroin is an exception = readily crosses BBB • Highly lipid soluble • Metabolized to Morphine • 10 time more potent than morphine • Codeine has little direct action on receptors • Brain eliminates opioids via active transport mechanism EXCRETION Opiates have variable ½ lives • About 10% of morphine is excreted in the urine unchanged. • Half-life morphine: 2 hrs; 90% of morphine eliminated within 24 hrs of administration • Half-life codeine: 3 to 6 hrs • Meperidine metabolized in liver. • Half-life meperidine: 3 ½ hrs • Methadone is not completely metabolized. • Half-life methadone: 10 to 25 hrs • Naloxone is completely metabolized in the liver. • Half-life naloxone: 1 ½ hrs Table 11.2 Opioid Pharmacokinetic Information Opioid pKa Time to Peak Bioavailability Blood Levels Half-Life Potency Compared to Oral Morphine 2.9–4.5 hr (oral); 1.5–4.5 hr (parenteral) 1.0 (oral); 2.0–3.0 (i.m.; s.c.) 8.21 15–40% (oral) 30–90 min (oral) Heroin 7.95 635% (oral); 53% (inhaled) 6–34 min (i.v.); 61 min (inhalation) 68 min (i.v.; inhalation) 2.5–3.0 (i.m.; s.c.) Codeine 8.21 90% (oral) 60 min (oral) 1.4–3.5 hr (oral) 0.10–0.15 (oral) Oxymorpho 8.17 ne 10% (oral) 90–120 min (oral) 7–11 hr (oral); 2 hr (i.v.) 3.0–7.0 (oral) Oxycodone 60–87% (oral) 30–120 min (oral) 3–6 hr (oral) 1.5–4.0 (oral) Morphine 8.28 Copyright © 2018, 2013, 2007 Pearson Education, Inc. All Rights Reserved NEUROPHYSIOLOGY: RECEPTORS AND OPIOID PEPTIDES Opiate Receptors • μ*, δ, κ, ORL1 • G-protein coupled receptors release second messengers • Activation postsynaptic = inhibitory • Activation presynaptically = inhibit release of other neurotransmitters Natural ligands: Endorphins, Enkephalins, Dynorphins, Endomorphins, Nociceptin OPIOID DRUGS • Agonists • Morphine – non-selective agonist • μ receptor full agonist • Kappa receptor partial agonist • with less affinity, full agonist at delta receptors • Heroin • Metabolites act as morphine in the brain • Codeine • selective full agonist, only at the μ receptor 19 NEUROPHYSIOLOGY: OPIOID ACTION Sites of Action in the CNS • Analgesia: Spinal Cord, Periaqueductal Gray • Reinforcement: Limbic System, VTA, NAC • Dependence: Periventricular Gray • Vital Life Functions (depresses 3 brainstem functions): Respiratory Center*, Vomiting Center, Cough Center EFFECTS EFFECTS OF OPIOIDS Peripheral NS/body • Nausea and vomiting Incereased parasympathetic NS activation • Pinpoint pupils • Sweating • Constipation • Problems with urination • Lowered sex hormones • Sexual problems in men and women On Sleep • Sleepy sensation, nodding off • Insomnia CNS EFFECTS • Hindbrain: decreased activity: reduced alertness, respiration, digestion • Midbrain: decreased activity: decreased motor activity, perception of pain • Forebrain: reward pathway activation: feelings of benefit to survival of individual or species (reward) * = strong + reinforcement supports dependence 23 EFFECTS ON HUMAN BEHAVIOUR AND PERFORMANCE • Subjective Effects • Visions/dreams occurring in nods • The rush • Mood effects • Performance • Slows down • Tolerance allows users to maintain productivity SELF-ADMINISTRATION NON MEDICINAL • Chipping- occasional usage, maintain normal lifestyle • Addiction- usually physically dependent, chasing the rush, avoiding withdrawal (needs 1 injection/day), daily focus is on obtaining the fix leaving little energy, time, resources for much else TOLERANCE • Rapid and extensive tolerance to most of opioid’s behavioural effects • Chronic Tolerance • When tolerance has developed to any opioid, there will be a tolerance to all other opioid. • Some degree of cross tolerance between opioids and alcohol TOLERANCE Daily intake of morphine and heroin in a human and a rhesus monkey, when allowed free access to the drug. In both species, intake slowly increases over time and there are no periods of abstinence or voluntary withdrawal. WITHDRAWAL • Not as dangerous as withdrawal from alcohol or barbiturates • Media creation • Sequence • • • • • • • First Signs: restlessness and agitation Yawning Chills and Sweating Goose Bumps Drowsy/Yen Sleep Cramps, Vomiting, Diarrhea Twitching of Extremities HARMFUL EFFECTS: ACUTE EFFECTS • High doses can cause respiratory distress and seizures • Comatose state with pinpoint pupils and severe depression of breathing leading to death (high doses) • High level of overdose non medical opioid users • Overdose caused by mixing with other drugs, loss of tolerance trying to recover, or in fact quinine poisoning • Opioid analgesic overdose the leading drug poisoning cause *see how to administer naloxone video posted under the lecture* HARMFUL EFFECTS: CHRONIC • Health • Constipation • Cancer promoter • Central Nervous System • Reduction in cerebral blood flow • Reproduction • Reduced levels of testosterone • Menstrual irregularities • Pregnancy complications and addicted babies • Lifestyle Effects • Expensive • Hepatitis and HIV/AIDS T REATMENT TREATMENT: DETOXIFICATION • Counselling, therapy to facilitate detoxification, mange relapse • Abrupt Approach (withdrawal initiation) • Abstinence or opioid antagonist (more intense but shorter overall) – sudden withdrawal in supportive environment • Tapering Procedure • Methadone, slow weaning to avoid of severe withdrawal and pharmacological support for symptoms • (10-28days) • Antagonist Therapies TREATMENT Maintenance Therapies • Methadone Maintenance – taken orally, prevents withdrawal symptoms for up to 24 hrs = 1x day admin, antagonizes heroin • Requires daily visits to a clinic • Buprenorphine • Newer drug, take orally by prescription • Does not require administration at a clinic • Suboxone • Buprenorphine + naloxone AGENDA • Source and use • Use • Pharmacology • Effects • Treatment 34