Lecture 11 Opioids: Dependence, Overdoses, and Drug Interactions

De Blasio

*Administration launches comprehensive effort to reduce opioid misuse and OD deaths across the city -city to make naloxone, OD-reversing medication, available without a prescription at participating pharmacies in NYC "Last year, this city experienced the equivalent of more than one fatal opioid overdose a day," said Mayor Bill de Blasio. Unintentional opioid-involved overdose deaths have increased by 56 percent since 2010, as a result of the use of heroin and opioid analgesics, such as oxycodone and hydrocodone. 79 percent of drug overdose deaths in 2014 involved an opioid, including opioid analgesics (prescription painkillers) and heroin. The rate of heroin overdose deaths increased for four consecutive years by 100 percent. Staten Island recorded the highest rate of heroin involved overdose deaths (11.5 per 100,000 residents) and the highest rate of opioid analgesic-involved overdose deaths (7.8 deaths per 100,000 residents); however, more than half of overdose deaths involving heroin occurred among residents of the Bronx and Brooklyn.

Who is Dying from Overdoses Most

*Bias in Prescribing -Who has greater access to prescriptions? -Also painkillers & anti-depressants? *White women in small rural cities (even some men) are dying at much higher rates than in the 90s, while whites in the largest cities and suburbs have steady or declining death rates

Medication Assisted Treatment (MAT)

*Naloxone (narcan): safe medication that can reverse opioid OD -no effect on alcohol or other drugs -2-3 min to start working -may require more than 1 dose -effects last 30 to 90 min -may cause withdrawls -emergency use -greater affinity for u opioid receptor that opioids *Methadone: daily dosing -Full agonist *Buprenorphine: 3-4X a week -partial agonist *Naltrexone: once a month at ER -antagonist *decreases -opioid use -opioid-related overdose deaths -criminal activity -infectious disease transmission *increases -social functioning -retention in treatment *But MAT is hihghly underutilized -relapse rates are very high -have to be careful how you ween people off because they can still experience withdrawls *Naloxone (Narcan) has an end ethyl *Naltrexone has an end 3 member ring -Similar, but have very different functions

Biomarkers for Addiction

*OPRM1: encodes for target of opioids - and varies from person to person -can variants predict likelihood of addiction *OPRM1 variant -Affects specific receptor levels in brain -Associated with increased risk for addiction, overdose severity *Highlights precise, personalized nature of addiction

Mechanism of Opioid Action

*Opioids bind to u opioid receptor -A GPCR -Binds to extracellular surface -GPCR then active, can interact with G proteins -> analgesia -or GPCR can activate B-arrestin -> decreased respiration and GI function -Some drugs: fit into the receptor and give more analgesic relief by less of the bad side effects *Design of better drugs with pain relief but not respiratory suppression

Combining Opioids with other Drugs

*Pain Killers -Opioids (e.g.,oxycodone, hyrocodone, morphine) -Combined with: Benzodiazepines Treating anxiety, insomnia, seizure disorders, muscle spasms -Depress the CNS -> sleepiness, respiratory depression, coma, death -41% increase in patients prescribed both between 2002 -2014 (2.5 million patients!!!) -Rate of ER visits for this situation increased 2004 to 2011 and overdoses tripled. -1 out of 3 unintentional overdose deaths involve these two drug classes *"Black Box Warning" *Number 1 behavior that leads to overdoses: alcohol. -depresses breath rate -Alcohol acts as a solvent, so it is more active and can flow right across membrane. Changes solubility, distributions, etc

Pharma Settlement in 2007 for lying about the dangers of Oxycontin to the Public

*Purdue Pharma and officers will pay $634 million in fines *Cephalon is paying $444 million to settle long-running state and federal probes *INSYS therapeutics in trouble for fentanyl cocktail prescription for non-cancer patients *More overdoses (usage of naloxone) than fires

Vietnam Vets

*Sanjay Jupta-How do you turn a new routine into second nature, Vietnam Vets and heroin addiction 90% in Vietnam fell to 5% once they returned to 5%

Making Prescribers Accountable

*Sending Drs letters saying that they prescribe more prescriptions than normal and one of their patients actually died from opioid addiction *NO GOVERNMENT —federal or state —can afford to ignore the nation's destructive opioid abuse epidemic, and Maryland's is no exception. The recently concluded General Assembly session resulted in a significant step forward, in the form ofa bill requiring that all prescribers of opioidsparticipatein the state's Prescription Drug Monitoring Program (PDMP) as a condition of their state licenses. In essence, a PDMP is a database that tracks patients' past access to prescription opioids, enabling physicians to confirm or deny suspicions that a particular patient might be "doctor shopping" to fuel an addiction. With appropriate privacy protections, the programs may also help authorities identify doctors who are engaged in inappropriate or even illegal practices. Previously, Maryland's PDMP had been voluntary, diminishing its practical impact;a General Assembly analysisshowed that only about 10percent of eligible doctors, pharmacists and other providers registered. In December, Gov. Larry Hogan's (R) heroin and opioid abuse task force recommended making it mandatory. The new law, which takes full effect July 1, 2018, mandates that physicians not only consult the PDMP database before prescribing opioids but also do so on a sustained basis throughout their treatment of particular patients. Mr. Hogan's signature on the bill, which passed both houses overwhelmingly, represents a promise kept for his administration. But while the legislature and the governor were taking this step forward, they were making another, more questionable move —albeit with little fanfare. Specifically, they abrogated a Maryland Board of Physicians rule, established in 2014 at the request of then-Gov. Martin O'Malley (D), that all doctors receive continuing medical education on the do's and do not's of pain management and opioid prescribing. Mr. O'Malley was responding toa surge in overdose deaths at the time. The requirement was in keeping with a wider national push for such required refresher courses, whichhave just been endorsedby a high-level advisory panel at the federal Food and Drug Administration.

leading Cause of Accidental Death in NYC

*opiod overdose is now the leading cause of accidental death in NYC and in the US, surpassing even motor vehicle accidents. overdose deaths are preventable, and with naloxone, you can save a life. *Opioid ODs are preventable -Most drug ODS involve opioids, including heroin and prescription pain killers -prescription painkillers such as oxycodone are growing cause of ODs -Naloxone is a mediation that reverses the effects of opioid ODs. it became legal to carry naloxone in NY in 2006 -Even though most people think that OD are immediate, most overdoses occur 1 to 3 hours after the drug is taken. Only ~1 in 8 ODs happen immediately after the drug was taken -Most ODs in NYC happen at home -Most ODs hare witnesses, meaning that someone else can call for help *Reduce your risk: -Avoid using alone -take care if you haven't used in a while -avoid mixing -don't be afraid to call 911 (law protects you from prosecution) -Get an OD rescue kit (naloxone)

John Oliver Shreds Pharmaceutical Industry Over America's Massive Opioid Crisis

*wti hmore than 250 millions Rx written each year, there are allegedly enough opioid painkillers going around to give a bottle to every american adult and still have plenty left over. And that has John Oliver fuming

Opioids for Chronic Pain

Campaign to destigmatize opioids was successful. -Over 10 years, per capita sales of opioid analgesics increased 600% in the U.S.

Opioid Epidemic in Americ

*2010 survey -An estimated 2.4 million Americans used prescription drugs non-medically for the first time within the past year, which averages to approximately 6,600 initiates per day.More than one-half were females and about a third were aged 12 to 17. -When asked how prescription opioids were obtained for nonmedical use, more than half of the 12th graders surveyed said they were given the drugs or bought them from a friend or relative. Interestingly, the number of students who purchased opioids over the Internet was negligible. -Persons aged 65 years and older comprise only 13 percent of the population, yet account for more than one-third of total outpatient spending on prescription medications in the United States. Older patients are more likely to be prescribed long term and multiple prescriptions, and some experience cognitive decline, which could lead to improper use of medications. *116 Million Americans struggle with chronic pain Long-term treatment -Tolerance, Hyperalgesia, Addiction • Antagonists -Naloxone • Pain relief, anesthesia, cough suppressants, suppressant of diarrhea • Bind opioid receptors in CNS, PNS and GI tract • Side effects -itchiness, sedation, nausea, respiratory depression, constipation, euphoria • Tolerance, Dependence and Withdrawl *On Wednesday afternoon, a police officer in East Liverpool, Ohio stopped a vehicle for driving erratically andmade a shocking discovery: The driver was barely conscious. A woman slumped acrossthe passenger seat next to him, turning blue. In the back of the vehicle, a 4-year-old boy sat restrained in a car seat, according to a police report. The officer called an ambulance, and when the EMTs arrived, they administered the life-saving drug Narcan--used to reverse opioid overdoses. Washington Post 9-9-16 Allen said authorities in East Liverpool, a city of 11,000 residents, are dealing with heroin-related cases on a daily basis. Other small cities are facing similar pressures. The city of Huntington, West Virginia (pop. 49,000) recently saw26 heroin overdose casesin a span of four hours. *The Charleston Gazette-Mail reports that police in Huntington, W.Va.,responded to 26 heroin overdose cases in a span of four hours on Monday evening. Huntington is a small city with a population of about 49,000 people, according to the Census Bureau. An overdose outbreak of similar magnitude in New York City (population 8.4 million) would affect more than 4,400 people. "Every ambulance in the city of Huntington went out in 10 minutes on these overdoses," Cabell County EMS director Gordon Merry told 13 News. He said all of the overdose victims were able to be revived using naloxone, a drug that reverses the effects of an overdose. *Heroin, in combination with other drugs, is now commonly causing overdoses. Opiate Cocktails -These combination overdoses, involving heroin and other powerful drugs such as the painkiller fentanylorthe sedative carfentanil, arebecoming more common. Nearly half of overdose death certificates included mentions of "unspecified" drugs in 2014. In nearly 20 percent of all overdose deaths, an "unspecified" drug is the only drug mentioned, meaning that authorities classified the death as an overdose but were not able to determine what drug caused it. The numbers underscore a key fact about buying drugs on the black market: Users often don't know exactly what they're going to get. Some users may seek out more powerful drugs like fentanyl and carfentanil for the more powerful high. But others may have no idea that these drugs may be included in the heroin they're getting from dealers. And dealers may not even know it themselves. *Carfentanil= 1000X than morphine *Fentanyl is 50 - 100X stronger than morphine

Krantom

*Kratom= Plant based opioid relief *According to DarshanSingh Mahinder, a professor at theCentre for Drug Research at the University of Science Malaysia, throughout Malaysia, the leaves of the kratomplant are traditionally crushed and made into a tea. It's used to "self-treat heroin/morphine dependence, or to reduce opiate withdrawal among illicit drug users," he said. It can also be used for pain relief. But in the United States, it's sold as a supplement, usually in the form of powder, pills, capsules or even energy drinks, and loosely regulated by the Food and Drug Administration. Christopher McCurdy, president-elect of theAmerican Association of Pharmaceutical Scientists, believes that kratomhas the potential to work for patients and even help solvethe opioid crisis. He believes that the success of the plant may lie in its two principal alkaloids, mitragynineand 7-hydroxymitragynine. These chemicals can bond to the body's opioid receptors and act very much like opioids do, providing some pain relief and causing a release of dopamine, but at a much more toneddown level than prescription pills or heroin. Users say there are mild, if any, withdrawal symptoms. McCurdy pointed out that his studies indicate that 7-hydroxymitragynine may have some addictive qualities, but when looked at in the entire plant, the ratio of that element is so little that the plant has very low abuse potential, one he likened to coffee. And unlike opiods, McCurdy said, kratomdoesn't slow breathing. And that's key. When people overdose on opioids, whether it is a legally prescribed oxycodone or illicit heroin, their body's respiratory system completely stops. *Incentive for Drug Development Low for Plant-based drugs (No patent) -Potential Scheduled I DEA Classification *Schedule I Drug List: Schedule I drugs are considered to have "no currently accepted medical use and a high potential for abuse -Heroin -LSD -Peyote -Marijuana -Ecstasy -THC -Fentanyl

Some headlines

*Investigation: The DEA slowed enforcement while the opioid epidemic grew out of control *How drugs intended for patients ended up in the hands of illegal users: 'No one was doing their job'

What is Fentanyl

Fentanyl is a powerful synthetic opioid analgesic that is similar to morphine but is 50 to 100 times more potent. It is a schedule II prescription drug, and it is typically used to treat patients with severe pain or to manage pain after surgery. It is also sometimes used to treat patients with chronic pain who are physically tolerant to other opioids. In its prescription form, fentanyl is known by such names as Actiq®, Duragesic®, and Sublimaze®. Street names for fentanyl or for fentanyl-laced heroin include Apache, China Girl, China White, Dance Fever, Friend, Goodfella, Jackpot, Murder 8, TNT, and Tango and Cash. *Overdose Prevention Resources for Providers -Overdose deaths from opioids, both opioid analgesics and heroin, are a public health crisis in New York City. These overdose deaths are preventable. -Naloxone, an opioid antagonist, can safely reverse an opioid overdose. In New York State, it's legal for anyone to carry and use it.

CDC Statement

In March 2016, CDC Director Dr. Tom Friedenwrote in the New England Journal of Medicine that there still aren't enough data about long-term use of prescription opioids. But, he wrote, "We know of no other medication routinely used for a nonfatal condition that kills patients so frequently." Most trials have lasted six weeks or less, and the few that have been longer had "consistently poor results." In fact, several studies have showed that use of opioids for chronic pain may actually worsen pain and functioning, possibly by increasing pain perception. Opioid dependence may be as high as 26% for patients using opioids for chronic non-cancer pain. One out of every 550 patients started on opioid therapy died of opioid-related causes a median of 2.6 years after their first opioid prescription.

Opioids on Trial

"Mississippi Attorney General Jim Hood —aided by a phalanx of private plaintiffs' attorneys—can proceed with a suit against opioid manufacturers in which the companies stand accused of promoting the drugs by allegedly systematically understating their health risks and exaggerating their benefits, violating state law. The potential exists for a mega-case like the one that ultimately brought Big Tobacco to heel. At a minimum, pretrial discovery might force drug companies to do something they have heretofore fiercely resisted: produce their internal records, including any that show discrepancies between what they told doctors, regulators and the public about opioids, and what they knew or suspected privately. Eyeing billions in profits, opioid companies bombarded the marketplace's gatekeepers — medical societies, academics, state legislatures, Congress and, crucially, the Food and Drug Administration —with a consistent, seductive message: Chronic pain affects tens of millions of adults and is woefully undertreated; and it can be safely and effectively eased, on a continuous basis, with opioids, contrary to long-standing medical wisdom." **Groups suing makers of opioids -Didn't exist before, pharma behind the scene pushing these things, increasing promotion, ethically wrong to leave people in pain (cultural shift in the late 80s. Dr must do everything they can to alleviate pain). Pharma was saying it's not addictive, you can give them to patients *If you take pain away you learn less

President Obama

"New policies to reduce inappropriate prescribing of prescription opioids such as Oxycontinand Vicodin. Given the ongoing epidemic of addiction and death caused by opioid painkillers, this seems like sensible public-health policy, but some critics charge that tighter prescribing rulessimply cause prescription opioid users to switch to heroin, thereby feeding a second opioid epidemic. The prestigious New England Journal of Medicine recently published the firstsystematic analysis of this terrifying possibility. Heroin use and heroin-related emergency-room visits and hospitalizations were rising for years before the 2009-2011 period in which controls of prescription opioids expanded —for example, by strengthening of state prescription-monitoring programs, crackdowns on pill mills and the introduction of an abuse-deterrent formulation of Oxycontin. Evidence that Mexican heroin traffickers made special efforts to expand into communities with established prescription opioid problems. As users become tolerant to the effects of opioids, they often consume an increasing amount of the drug until they simply cannot afford to purchase the dozens of pills they want each day from legal or illegal sources. Heroin, which once may have seemed unthinkable, thus becomes attractive because of its affordability."

Mexican traffickers making New York a hub for lucrative —and deadly —fentanyl,

*"Most of the [213 pounds] —141 pounds —was pure fentanyl, a synthetic and supremely dangerous opioid 50 times more powerful than heroin. It was the largest fentanyl seizure in U.S. history. There was enough inside the apartment to kill 32 million people, according to the Drug Enforcement Administration." *"Although the opioid boom hasn't led to more violence in New York, it has produced a staggering amount of death. The city had nearly, 1400 fatal overdoses last year, a 46% increase from 2015. Fentanyl showed up in 44% of autopsies." *"...narcotics agents can no longer cut open packages to conduct field tests. The fentanyl is too dangerous; even a dusting of airborne powder can trigger an overdose."

History of Heroin

*1898 Bayer started producing heroin -cough suppressant, pain reliever *1900 Civil War veterans addicted to morphine from war injuries *1914 Harrison Narcotics Tax Act -tax on import or sale of opium derivative or coca leave derivative *1920s -Doctors aware of highly addictive nature of opium *1924 -Heroin became illegal WWII "turning point" *1950s to 1960s -Anesthesiologist opened up "nerve block clinics" Doctors taught not to prescribe highly addictive opioids *1970s -Gerald Ford's drug task force recommended focus on heroinepidemic Then Percocet (Endo Pharmaceuticals) and Vicodinentered the market *1980 NEJM Reversal by Jane Porter & Herschel Hicks -Opioids less risky for treating chronic pain (11,882 patients), 1% die Patients then started treatment for terminal illness and chronic pain. *1986 -Russell Porenoy (2/38 patients addiction) opioids can be humane way to treat chronic pain or avoid surgery *1990s -Focus on pain as the fifth vital sign *1996-Birth of Oxycontin(Purdue Pharma) -2-3 M, then jump to 8 M prescriptions per year, then 11 M *2007 Purdue charged with misbranding and downplaying addiction, $635M settlement *2001 -2009 Joint Commission promoted pain management with opioids *2010 Oxycontinreleases "abuse deterrent" form, which prevents snorting or injection; however, pushed users to heroin. *2011 -Portenoy recants his statements. *2016 FDA announced that immediate-release opioid painkillers such a oxycodone and fentanyl will now have to carry a "black box" warning about the risk of abuse, addiction, overdose and death.

Synergistic Effects of Opiates and Psychotropics

*Additive effect on respiratory depression by benzodiazepines and opiates *Increased risk of serotonin syndrome and seizure when using tramadol with selective serotonin reuptake inhibitors or tricyclic antidepressants *Additive prolongation of the QTc interval by methadone when used with psychotropics known to prolong the QTc, such as ziprasidone. *Typically, Opioids should NOT be used with other substances that depress the CNS, such as alcohol, antihistamines, barbiturates, benzodiazepines, or general anesthetics, because these combinations increase the risk of life-threatening respiratory depression. *Psychotropic or Psychoactive drugs change brain function, mental activity, behavior or perception -"mood altering" *Opioids -all drugs with morphine-like effects (sedative, depressant, anesthetic, analgesic), including natural and synthetic and semi-synthetic Opiates *Anti-Psychotic drugs or Neuroleptics or Major Tranquilizers block dopamine receptors to treat psychosis (delusions, hallucinations, paranoia or disordered thoughts) in schizophrenia, biopolardisorder (lows and mania) *CNS Depressants -Sedatives and Tranquilizers -slow brain activity, by increasing the GABA (gamma aminobutyric acid) inhibitory neurotransmitter -> drowsy or calming effect. Often prescribed for anxiety and sleep disorders. Include Benzodiazepines (Valium or Xanax or Halcion or ProSom), Barbiturates (Nembutal), Non-Benzodiazepine sleep meds (Ambien, Lunesta, Sonata)

*CYP2D6

*CYP2D6 and codeine *Codeine to morphine: hydroxylate it (CYP2D6) (convert methyl ether (C) to alcohol(M)) -Codeine is not very good at pain relief, morphine is *CYP2D6 encodes a cytochrome P450 enzyme CYP2D6 that detoxifies drugs in the liver. CYP2D6 is responsible for metabolism and elimination of 25% of clinically used drugs. Also metabolizes hydroxytryptamine and neurosteroids. But it also is the primary cytochrome P450 enzyme that metabolizes codeine. -Codeine -> Morphine via CYP2D6 *Thus, genetic Variation in CYP2D6 leads to Codeine metabolism as follows: -UM (ultrarapid metabolizers, CNV) -> High Morphine levels (TOXICITY) -EM (extreme metabolizers, wildtype) -> Low Morphine levels (EFFICACY) -PM (poor metabolizers, variant) -> No Morphine levels (NO EFFICACY) *Ethnic Variability exists in CYP2D6 -> Clinical Variability in Drug Responsiveness and Dosing *Since Morphine has much stronger analgesic (pain relief) properties relative to codeine, PM patients do not find pain relief when taking codeine. *Mutations -WT: CYP2D6*1 -Increased Activity:CYP2D6*2 -Decreased Activity: CYP2D6*9, CYP2D6*10, CYP2D6*17 *Genetic difference: -Many UM in Greece, Italy, Spain (1% frequency) *Certain regions or groups that are more predisposed to have overdoses based on UM allele -Gene duplication / multi duplication: Ethiopians and Saudi Arabians: 10-16% *Codeine is well established and clear cut in literature, everything else isn't necessarily *Measuring 10,000-Fold Variation in CYP2D6 Activity in UM, EM and PM Patients *CYP2D6: codeine, hydrocodone, methadone, oxycodone (all also include other CYP metabolites such as 3A4 except for codeine)

People can become dependent on prescription painkillers and suffer serious problems

*Craving *Mixing drugs *Tolerance *Loss of control: difficulty stopping or cutting down even when taking the medication is causing health, money, or legal problems *Withdrawl: feeling sick when medication is stopped *Blackouts: forgetting all or part of what happens when using *preoccupation: thinking a lot about getting and using a medication; neglecting family, friends, work, or school

SCREENING PATIENTS TO IDENTIFY UNUSUAL PAIN RELIEF REQUESTS

*Cytochrome P450 Testing In High-dose Opioid Patients *"A major reason to perform CYP450 genetic testing is to identify pain patients who legitimately require a high-dose, or unusual, opioid regimen.2,22 This includes patients who continually complain of inadequate pain relief despite standard opioid dosages, identify drugs that are more effective, or describe medicines that do not work well. Patients with a daily morphine equivalent dosage requirement of more than 150 mg per day should be tested to help validate that a high opioid dosage is needed. Caution must be exercised, however. All too often, these patients may be erroneously labeled as drug seekers or addicts." *If CYP450 deficiencies present, then utilize hydromorphone, oxymorphone, or tapentadol as these opioids are primarily metabolized by glucuronidation, the alternate opioid metabolism system.

Opiate Advertisement, People who died

*Easy home guide to overcoming addiction, *Heroin - Hydrochloride: cough relief *A designer thought this pill-themed high fashion line was clever. Drug counselors begged to differ, Wash Post -To New York magazine it was a winking reference to the "Valley of the Dolls." Even the slogan, "just say Moschino," was an echo of the '80s, remixing the famous words of war-on-drugs crusader first lady Nancy Reagan -phone case, purse, shirt *Jim Carroll, Prince, Janis Joplin, Kurt Koban

The Black and White of Heroin -The poisoning of America

*Heroin is cheaper than Prescription Pain Killers Mexican Black Tar Heroin *Average age 24 years old in US Experimented with pain killers, moved on to heroin *$10 / bag of heroin *Shift in law enforcement -> drug treatment programs for addicts *Racial divide between jail time vs. drug treatment *1/6 inmates at Cook County Jail used heroin in days before arrest *Blacks are 8X more likely to be stopped and frisked, so drugs will be found more often and then less likely to be offered a drug treatment option

Politico Explains: Opioids

*How did we get here -Pain is the 5th vital sign (1996) -Drs overprescribe opioids -Pharma pushing -Minimized addiction potential -patients relief on quick fix -Reimbursement of Drs $$ for pain killer Rx -Switch from painkiller Rx to street illegal opioids *How can we solve it -Less and weaker Rx written -Physical therapy and counseling -Insurance must cover $$ treatments -Medical staff retraining (will take 10 years for new training to make it into a majority of practices_ -Prevent Dr shopping -FDA stronger label warnings -patients with a slower healing process *How can we help addicts -Convert jail time to clinical support -Competitors that are not addictive -Prevent overdose - naloxone -Federal $$ -> treatment centers -Pharma and Drs need t change policy

Opiates and Opioids, Definitions and Derivations

*In the opium poppy: From L-tyrosine -> 9 enzymatic reactions -> (5)-reticuline (has other methylated derivatives) -> 7 enzymatic steps -> morphinone and codeinone -Later becomes morphine and codeine *Figure 1: In aerial parts of the opium poppy, including unripe seed capsules (background), the analgesic alkaloids morphine and codeine are synthesized from the amino acid tyrosine via multiple enzymatic steps, with reticuline as an intermediate. Blocking a terminal biosynthesis step leads to complete loss of all morphine-type alkaloids from the poppy latex, and to accumulation of reticuline and methylated reticuline derivatives, which normally do not occur at appreciable levels. *Opiates are a subset of opioids *Opoiods -Opiates -Synthetic opiates (Vicodin, percocent, oxycodone, fentanyl) *Opiates (derived from poppy) -opium -Morhpine -Heroin -Codeine *Derivatives of morphine -codeine -oxycontin (oxycodone) -fentanyl -heroin (diacetylmorphine) -methadone -carfentanil

Overdose Death Rates

*Increased drastically since 1999 -worse: SW but not california, right under great lakes but slightly east *In 2011, 4 M Americans recreationally use opioids. *In 2013, 28 -38 M used illicit opioids worldwide. *Heroin overdose deaths have risen drastically in recent years, according to the CDC. -The drug killed over 10,000 people in 2014 -Over 12,990 heroin overdose deaths in 2015, *20,101 prescription drug (opioid) overdose deaths. Surpassed gun homicides in 2016. -23% of Heroin users develop opioid addiction *Global estimates of illegal drug users in 2014 (in millions of users) World Drug Reports 2016 -UN -Opioids: 33.12 -Opiates: 17.4