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PSY 320 - Ch 13 - Opioids

by: Elliana

PSY 320 - Ch 13 - Opioids PSY 320

Marketplace > University of Miami > Psychlogy > PSY 320 > PSY 320 Ch 13 Opioids
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Combined class lecture & textbook notes
Drugs & Behavior
Dr. Marc Gellman
Class Notes
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This 12 page Class Notes was uploaded by Elliana on Sunday March 27, 2016. The Class Notes belongs to PSY 320 at University of Miami taught by Dr. Marc Gellman in Spring 2015. Since its upload, it has received 20 views. For similar materials see Drugs & Behavior in Psychlogy at University of Miami.


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Date Created: 03/27/16
PSY 320 Drugs & Behavior Chapter 13 Opioids Opioids • Psychoac▯ve substances that elicit pharmacological effects by ac▯ng on opioid receptors in CNS & other parts of body ◦ Prescrip▯on pain medica▯ons & non medical use of heroin ◦ Highly effec▯ve pain-relieving medica▯ons ◦ Substances of abuse • Narco▯c: La▯n for "sleep inducing" ◦ Though opioids are used as analgesics rather than sleeping aids • Natural opioids - found in opium exudant from poppy plants ◦ Paver Somniferum ◦ Substances derived from opium poppy ◦ Primary naturally occurring opioids found in opium - Morpheme & Codeine • Semisynthe▯c opioids - synthesized from morphine or codeine ◦ Created from naturally occurring hydromorphine, hydrocodone, oxycodone, diacetyl morphine (heroin) • Fully synthe▯c opioids - not derived from any naturally occurring opioid ◦ Fentanyl, methadone History Ancient history • Opium - Raw plant substance containing morphine & codeine • One of the oldest discovered drugs • Sumerians in Mesopotamia were among first ppl iden▯fied to have cul▯vated poppy plant CB 00 43 dnuo◦r A ◦ Hul Gil - "The Joy Plant" ◦ Eaten to ease pain/suffering • 1500 BC Ancient Egyp▯an medical textbook described medical uses • Opium use eventually spread thru ancient world to every major civiliza▯on in Europe & Asia & was used to treat pain/ailments PSY 320 Drugs & Behavior • 400 - 300 BC Greece & Rome ◦ Hippocrates detailed sleep inducing & pain relieving effects of opium ◦ Galen also promoted beneficial effects for a range of ailments • 900 - 1100 AD Arabic world ◦ Arab physicians wrote widely about medical use ◦ Wrote about addic▯ons & medical prac▯ces ◦ Spread to India & China thru trade ◦ Used as social drug Opium Wars • 1644 Tobacco smoking banned in China • Contributed to increase in opium smoking • Opium smoking in combina▯on w/ tobacco gained popularity ◦ Rapid absorp▯on/onset of effects • 1729 Chinese law banned opium smoking, mandated opium shop owners be strangled • Smuggling business grew • Britain profited from trading w/ China & selling opium • 1839 - Opium Wars set off by Bri▯sh sailors killing a Chinese ci▯zen ◦ Britain won in 2 yrs • 1906 Britain passed a bill to end the opium trade by 1913 Pa▯erns of Abuse in the US • Transforma▯on of the prac▯ce of medicine ini▯ated tension btwn desire to make medicinal benefits available & recogni▯on of abuse & addic▯on • 2 benefits: ◦ Reduces diarrhea & subsequent dehydra▯on from dysentery, a leading cause of death in developing countries ◦ Relieves anxiety • 1803 morphine was extracted from opium by Friedrich Serturner in Germany • Dr. Charles Wood (Sco▯sh physician) invented hyperdermic needle to inject morphine to relieve pain from neuralgia • Dr. Eduard Livenstein (German physician) produced 1st accurate & comprehensive descrip▯on of addic▯on to morphine, including withdrawal symptoms & relapse ◦ Argued that craving for morphine was a physiological response • Diacetylmorphine (brand name Heroin) synthesized & briefly promoted as more effec▯ve & less addic▯ve than morphine • Early 1900s Heroin was legally marketed in pill form, used by young Americans to elicit euphoric high by crushing heroin pills into powder for inhala▯on or injec▯on • 3 types of dependence developed in the US in the late 1800s ◦ Oral intake increased as patent medicines spread ◦ Opium smoking increased a▯er 1850 • Chinese laborers arrived in the US ◦ Injec▯on of morphine - the most dangerous use • Number & propor▯on of Americans dependent on opioids peaked in the beginning of 1900s ◦ Possibly as high as 1% of the popula▯on • Dependence ini▯ally not viewed as a major social problem ◦ Opium smoking limited to certain groups ◦ Patent medicines socially acceptable PSY 320 Drugs & Behavior ◦ Opioid dependence viewed as a "vice of middle life" • Typical uses 30-50 y/old middle class white women wives/mothers • Drugs purchased legally in patent medicines • High levels in medicines made withdrawal symptoms severe & relieved only by consuming more 1914 Harrison Act • Revenue regula▯ons • Affected court decisions & enforcement prac▯ces • 1915 Supreme Court decided possession of smuggled opioids was a crime • 1920s opioid clinics were closed due to pressure from federal officials • Number of oral opioid users declined ◦ Remaining group primarily injected morphine or heroin • Increased prices of illicit heroin lead to increased use in lower-class city areas ◦ Heroin became associated w/ black & La▯no users • 1973 Rockefeller Drug Laws ◦ Mandated minimum prison sentences of 15 yrs-life for possession of heroin in New York ◦ 2009 reformed by Gvnr Pa▯erson to reduce harsh sentences Vietnam War • ~1960s/70s • 10-15% of soldiers dependent on heroin ◦ Most returning soldiers were not dependent ◦ Only 1-2% con▯nued use 8-12 months a▯er returning from Vietnam Current Trends • Popular prescrip▯on opioids: ◦ Hydrocodone (Vidocin, Lortab) ◦ Oxycodone (Oxycon▯n, Percocet) • Prevalence of use: ◦ 2012 - 2% / 12 million Americans reported past year use ◦ Routes of administra▯on include oral, insuffla▯on, injec▯on • Safety concerns: ◦ DAWN data: prescrip▯on opioids rank 3rd for ER visits & 1st for deaths ◦ Most opioid overdoses occur in combina▯on w/ other seda▯ves like alcohol • Special problem of Oxycon▯n (Schedule II drug) ◦ Illicit users crush capsules to obtain a high dose Prescrip▯on opioid abuse: A first step to heroin use? • Prescrip▯on opioid pain medica▯ons like Oxycon▯n & Vicodin have similar effects to heroin when taken in doses/other ways than prescribed ◦ Currently among most commonly abused drugs in the US • Research suggests abuse of these drugs may open the door to heroin abuse • In 3 recent survey studies: almost half of young ppl who inject heroin reported abusing prescrip▯on opioids before star▯ng to use heroin ◦ Some individuals reported taking up heroin b/c it's cheaper & easier to obtain than prescrip▯on opioids ◦ Many report that crushing prescrip▯on pills to snort or inject provided their ini▯a▯on to these methods of drug administra▯on PSY 320 Drugs & Behavior Treatment of Chronic Pa in During most of 1900s: • Widely held percep▯on among US professionals was long-term use of opioid therapy to treat chronic pain was contraindicated by risk of addic▯on ◦ Increased disability & lack of efficacy over ▯me During 1990s: • Major change driven by medical & nonmedical factors • Use of opioids for chronic pain increased • Substan▯al year-to-year rise that con▯nues today • Increased use for medical purposes accompanied by increase in prevalence of nonmedical use of prescrip▯on opioids • Inven▯on of PCA pump for pa▯ents to control morphine flow a▯er surgery ◦ Found pa▯ents consumed less morphine when controlling it themselves Increases in prescrip▯on use: • Na▯onal Survey on Drug Use & Health reports # of first ▯me abuses of prescrip▯on opioids increased from 628,000 in 1990 to 2.4 million in 2004 • Emergency room visits involving prescrip▯on opioid abuse increased 45% from 2000 to 2002 • Treatment admissions for primary abuse of prescrip▯on opioids increased 186% from 1997 to 2002 • Opioid abuse indices rose most for 2 frequently prescribed opioids: ◦ Hydrocodone & controlled-release (CR) oxycodone Current public health crisis: • March 22, 2016: FDA announced enhanced warnings for immediate-release opioid pain medica▯on (oxycodone) ◦ Related to risk of misuse, abuse, addic▯on, OD, & death • "Opioid addic▯on & overdose have reached epidemic levels over the past decade" • FDA's ac▯ons one of the largest undertakings for informing prescribers of risks across opioid products Public health crisis background: • In any given year, approx. 100 million ppl in the US suffer chronic pain • 9-12 million have chronic/persistent pain, while the remainder have short-term pain from injuries, illnesses, or medical procedures • All should benefit from appropriate pain management: sen i c i dem d i o i po f o esu s uo i c i d◦ u J ◦ In conjunc▯on w/ other methods of treatment • In reality, physicians have been over-prescribing ◦ Short-term injury sufferers prescribed months worth of medica▯ons ◦ Seek prescrip▯ons from other doctors or illicit providers • Current crisis due to the devasta▯ng results of misuse/abuse • Leads to addic▯on of pa▯ents who've been prescribed opioids for pain treatment & increasingly diversion to ppl for whom the prescrip▯on was not wri▯en • # of annual opioid prescrip▯ons wri▯en in the US roughly equal to # of adults in the US • CDC: In 2014 there were 19,000 OD deaths in the US associated w/ prescrip▯on opioids • # of deaths from opioid overdoses now exceeds the # of deaths caused by motor vehicle accidents PSY 320 Drugs & Behavior • New FDA warnings (03/22/16) indicate b/c of extreme risks associated w/ use of IR opioids, they should be reserved for trea▯ng pain severe enough that alterna▯ve treatment op▯ons are inadequate • New boxed warning on IR opioid analgesics: ◦ Requires precau▯on against maternal use ◦ Use during pregnancy can result in neonatal opioid withdrawal syndrome (NOWS) ◦ Baby withdrawals may be fatal 3rd category of opioids: • Known as medica▯on-assisted treatment (MAT) • Drugs such as methadone & buprenorphine • Used as form of treatment for opioid addic▯on • In combina▯on w/ behavioral therapy & counseling Opium Characteris▯cs • Raw opium 10% morphine by weight • With added acetyl groups, heroin passes thru blood-brain barrier faster ◦ Makes heroin 2-3x more potent than morphine • Researchers have been searching for ways to separate analgesic & dependence-producing effects of opioids Pharmacology: Mechanism of Ac▯on • Opioids act on selec▯ve receptors in the CNS & gastrointes▯nal tract • Opioids ac▯vate: ◦ Enkephalins - Morphine-like neurotransmi▯ers found in the brain & adrenals • Released from adrenal gland ◦ Endorphins - Morphine-like neurotransmi▯ers found in the brain & pituitary gland • Released from pituitary in response to stress • Natural & synthe▯c opioid drugs & endogenous opioids act on mul▯ple types of opioid receptors in the brain • Body can naturally release its own morphine-like substances for survival: ◦ I.E. Soldiers ba▯ling thru injuries or women enduring natural child birth More on Mechanism of Ac▯on • Ac▯va▯on of peripheral nocicep▯ve fibers cause release of substance P & other pain-signaling neurotransmi▯ers from nerve terminals in the dorsal horn of spinal cord • Release of pain-signaling neurotransmi▯ers is regulated by endogenous endorphins or by exogenous opoid agonists by ac▯ng presynap▯cally to inhibit substance P release, causing analgesia • Reduc▯on or inhibi▯on of neurotransmission due largely to opioid-induced presynap▯c inhibi▯on of neurotransmi▯er release • Involves changes in tansmembrane ion conductance ◦ Increase potassium conductance (hyperpolariza▯on) ◦ Inac▯va▯on of calcium channels • Opioid receptors: ◦ Mu-1 - Found throughout the brain, responsible for analgesia & euphoria ◦ Mu-2 - Found throughout the brain, responsible for respiratory depression ◦ Kappa - Located in the brain stem & spinal cord, responsible for contrac▯on of eye pupils & seda▯on PSY 320 Drugs & Behavior ◦ Sigma - Located in the amygdala, hippocampus, & limbic system, responsible for anxiety & hallucina▯ons ◦ Delta - Located in the limbic system, responsible for analgesia as well as reinforcing proper▯es • Opioids almost always operate on receptors: ◦ Mu ◦ Kappa ◦ Delta Pharmacological Effects • Pain Relief ◦ Diminish pa▯ent's awareness/response to pain • Primarily emo▯onal response to pain (suffering) ◦ O▯en used to reduce pain w/o inducing sleep, though many pa▯ents become drowsy • Seda▯on & anxiolysis ◦ Drowsiness & lethargy ◦ Apathy ◦ Cogni▯ve treatment ◦ Sense of tranquility • Some cogni▯ve impairment • Some memory loss • Depression of respira▯on ◦ Main cause of death from opioid overdose ◦ Combina▯on of opioids & alcohol especially dangerous • Cough suppression ◦ "An▯tussive" ◦ Opioids suppress "cough center" in the brain (medulla) ◦ At high doses, produces hallucinogenic effects by blocking a type of glutamate receptor • Pupillary constric▯on ◦ Pupillary constric▯on in the presence of analgesics characteris▯c of opioid use • Nausea & vomi▯ng ◦ S▯mula▯on of receptors in the medulla (chemoreceptor trigger zone) causes nausea & vomi▯ng ◦ Unpleasant, but not life threatening side effect • Gastrointes▯nal symptoms/disorders ◦ Relieve diarrhea due to direct ac▯ons on intes▯nes ◦ Counteracts diarrhea, prevents death by dysentery (severe intes▯nal infec▯ons) • Other effects: ◦ Opioids can release histamines causing itching or more severe allergic reac▯ons including bronchoconstric▯on ◦ Opioids can affect white blood cell func▯on & immune func▯on Marke▯ng Cul▯va▯on • Produced & available for collec▯on for only a few days of the plant's life ◦ Opium harvesters use sharp clawed tools to make shallow cuts in the unripe seedpods PSY 320 Drugs & Behavior ◦ Resinous substance oozes out of cuts & is collected ◦ Raw opium is the substance from which morphine is extracted & heroin is derived Current Opium Produc▯on • Worldwide opium produc▯on is increasing • Driven by a sharp rise in poppy cul▯va▯on in Afghanistan ◦ Afghanistan currently #1 producer of the drug • During Taliban rule: produc▯on significantly decreased • A▯er US toppled Taliban in 2001, produc▯on increased again • Opium exports make up large por▯on of Afghanistan's GDP • DEA Sta▯s▯cs: Afghanistan's produc▯on of oven-dried opium increased to 1,278 metric tons a▯er US's invasion in 2002 • DEA Sta▯s▯cs: Produc▯on more than doubled by 2003, doubled again in 2004 • UN considers Afghanistan accountable for 92% of world's opium supply • 2009 opium exports from Afghanistan valued at $2.8 billion Prescrip▯on Analgesics • Natural products: ◦ Morphine en i e◦o C • Semisynthe▯cs ◦ Heroin • Synthe▯cs ◦ Methadone ◦ Meperidine ◦ Oxycodone *popular e nohpro my◦x O ◦ Hydrocodone *popular ◦ Hydromorphone en i edo co rdyh◦i D ene hpyxopo◦r P ◦ Pentazocine ◦ Fentanyl • Opioid Antagonists - Drugs that block the ac▯on of morphine, heroin, or other opioid agonists Morphine - the primary ac▯ve agent in opium • 1806 ac▯ve ingredient in opium isolated ◦ 10x as potent as opium • Named morphium a▯er Morpheus, god of dreams • 150 years a▯er commercial introduc▯on, morphine con▯nues to be most valuable postsurgical analgesia available • Sympoma▯c relief of moderate to severe pain • Relief of certain types of labored breathing • Suppression of severe cough • Suppression of severe diarrhea • 1853 hypodermic syringe invented to deliver morphine directly to the blood/▯ssue ◦ Believed that injec▯ng reduced risk of cravings - disproved • Injec▯ons used on soldiers in the American Civil War, Prussian-Austrian War, & Franco-Prussian War PSY 320 Drugs & Behavior ◦ Relieved pain & dysentery ◦ Returning veterans were dependent ◦ "Soldier's disease" or "Army disease" Codeine - the secondary ac▯ve agent in opium • Isolated alkaloid discovered in 1832 • Highly effec▯ve cough suppressant & moderate analgesic • Once available OTC, now requires prescrip▯on Heroin - diacetylmorphine, a potent deriva▯ve of morphine • Heroin = Diacetylmorphine ◦ 1874 - 2 acetyl groups were a▯ached to morphine ◦ 1989 - marketed as Heroin (brand name) by Bayer • 3x as potent as morphine ◦ Due to increased lipid solubility of the heroin molecule ◦ Lipid contents of brain hold morphine ◦ Faster absorp▯on & onset • Originally marketed as non-addic▯ve cough suppressant ◦ Replacement for codeine & morphine ecnedneped o t dekn i l r e t◦ a L • Produc▯on & Purity: ◦ Most heroin used in the US is derived from poppies grown in Mexico & Colombia ◦ Purity of heroin has increased drama▯cally in recent years • Mid-70s: purity 5% • 1980s: 25% • Currently: 20-40% ◦ Heroin: 0.2% of Americans report past year use Oxycon▯n • Opium derivate available by prescrip▯on • Extremely potent & addic▯ve analgesic • Prescribed to cancer pa▯ents & chronic pain sufferers • Comes in ▯me release tablets designed to be swallowed whole • Abusers can crush pills to snort or inject powder ◦ Rapid absorp▯on Fentanyl • Pharmacokine▯cs: ◦ Routes of administra▯on - Oral, transdermal, possibly intravenous ◦ Highly lipophilic ◦ Latency to onset - 7-15 min oral, 12-17 hrs transdermal ◦ Dura▯on of ac▯on - 1-2 hrs oral, 72 transdermal ◦ 80-85% plasma protein bound ◦ 90% metabolized in the liver to inac▯ve metabolites • 80x the analgesic potency of morphine • 10x analgesic potency of hydromorphone • High efficacy for MU 1 receptors • Most effec▯ve opiate analgesic Dependence Poten▯al PSY 320 Drugs & Behavior Tolerance • Tolerance develops to most effects from both medical & recrea▯onal usage ◦ Higher doses needed to maintain effects • Cross-tolerance exists among all opioids • Psychological processes play key role in tolerance ◦ Dependent individuals develop a condi▯oned reflex response to the s▯muli associated w/ taking the drugs ◦ Animal experiments show that placebo injec▯ons produce body changes opposite to those produced by morphine ◦ Shows the body counteracts an▯cipated effects of the drug • Behavioral tolerance: ◦ Rats adjusted to high consump▯on of heroin injec▯ons ◦ Rats given the same amount in a new environment mostly died ◦ Showed that tolerance reflexes are environment-specific ◦ Condi▯oning is very crucial to tolerance Physical Dependence • Symptoms of withdrawal appear in sequence following the ▯ming of the most recent dose & the individual's history of use • Opioid withdrawal is unpleasant, but rarely life-threatening ◦ Not necessary to be medically supervised during withdrawals ◦ Withdrawals feel similar to the flu (vomi▯ng, diarrhea, aches, pains, etc.) • Methadone: ◦ Long-las▯ng synthe▯c opioid ◦ Produces withdrawal symptoms that appear later & are less severe than those from heroin • May last longer Reinforcing Effects • Subjec▯ve effects occur during 4 phases: ◦ Rush - ini▯al/rapid onset of euphoria ◦ High - feelings of joy/goodwill ◦ Nod - calm, disinterest, unawareness of surroundings ◦ Straight - period of normalcy • Subjec▯ve effects of opioids readily pair w/ environmental s▯muli ◦ Condi▯oned place preference procedures are used to study reinforcing effects of opioids like heroin Psychological Dependence • Posi▯ve reinforcement - posi▯ve effects reliably follow use of the drug (rapid onset of effects) • Nega▯ve reinforcement - use of the drug removes withdrawal symptoms ◦ Appearance of early withdrawal symptoms just hours a▯er injec▯on typically leads to stronger dependence • Fast-ac▯ng injectable opioids are most likely to lead to dependence • Needle habit: ◦ Each heroin administra▯on is followed by: • A decrease in discomfort • An increase in pleasure deno▯ i dnoc em oc eb s r e◦s U PSY 320 Drugs & Behavior ◦ Process of using heroin becomes rewarding in itself PSY 320 Drugs & Behavior Toxicity Poten▯ al Acute Toxicity • Opioids depress respiratory centers in the brain ◦ Breathing becomes slower & shallower • Respiratory depression is the primary cause of death from OD • Opioid overdose triad: ◦ Coma no▯a r i pse r des se rp ◦e D ◦ Pinpoint pupils • Clouding of consciousness Chronic Toxicity • Associated w/ injec▯on method • Infec▯ons & spread of blood-borne diseases (HIV, hepa▯▯s) • Constant pain suppression may conceal early symptoms of illnesses like pneumonia • Lack of money & food may cause malnutri▯on ◦ Increased suscep▯bility to diseases Misconcep▯ons & Preconcep▯ons • Not all users experience euphoria from ini▯al dose • Many experience nausea/discomfort • Tolerance to nega▯ve effects may develop more rapidly than tolerance to posi▯ve effects • Withdrawal o▯en similar to mild case of intes▯nal flu • Ppl don't become dependent a▯er 1 dose, takes ▯me & persistence Trea▯ng Opioid Addic▯on • Pharmacological treatments for opioid addic▯on include: ◦ Detoxifica▯on - Process that uses an opioid agonist or antagonist to reduce withdrawal symptoms ◦ Management of comorbid disorders • Opioid Antagonists: ◦ Drugs that block the ac▯on of opioids ◦ Examples: Naloxone, nalorphine ◦ Effects: • Reverse depressed respira▯on from opioid OD • Precipitate withdrawal syndrome • Prevent dependent individuals from experiencing a high from subsequent opioid use • Naltrexone ◦ Use of injectable, intranasal, & intramuscular efforts to develop new ways of administering drug to save lives ◦ Carried by doctors, first-responders, police, etc. for emergencies ◦ Can be used to stop overdoses ◦ 3/23/16 - Canada decided Naloxone can be available w/o prescrip▯on • EVZIO - FDA approved Naloxone auto-injector • All examples of medicinal responses to abuse/OD rates ◦ Pharmacokine▯cs: • Latency to onset - oral tablet 15-30 min • Dura▯on of ac▯on - 24-72 hrs • Peak effect - 6-2 hrs PSY 320 Drugs & Behavior ◦ Structural dis▯nc▯on: • Differs from Naloxone since the allyl group on nitrogen atom is supplanted by cyclopromethyl group ◦ Effects: • Reverses psychotomime▯c effects of opiate agonists • Reverses hypotension & cardiovascular instability secondary to endogenous endorphins (potent vasodilators) • Inhibits Mu, Delta, Kappa receptors • Clonidine ◦ Alpha-adrenergic agonist • Alpha-adrenergic receptors found together w/ opioid receptors in the brain ◦ Treats high blood pressure ◦ Can diminish severity of withdrawal symptoms • DEA released documentary aimed at educa▯ng students & young adults about dangers of addic▯on - "Chasing the Dragon"


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