MEDICAL TOXICOLOGYANDOPIOID ABUSE

Fred Harchelroad, MD FACEP, FAAEM, FACMT

Westmoreland Emergency Medicine Specialists

Excela Health System

DISCLOSURE

I am an emergency medicine physician working

for more than three decades. My reality is biased

by all those patients with whom I have interacted.

OBJECTIVES

• Better understanding of the history of opioids.

• Compare and contrast an opiate and an opioid.

• Discuss the utility of commonly used urine drug screens.

• Critique the efforts to manage opioid abuse in your area.

• Differentiate the different opioid detox/rehab options.

POPPY LANCING

OPIOIDS THROUGH-OUT HISTORY

• Sumarians (4000 B.C.) “hul gil” = joy plant = poppy

• Ebers papyrus (1500 B.C.) milk of poppy helped infants sleep

• Theophrastus (300 B.C.) written reference of opium.

• Paracelsus (1493–1541) compounded laudanum (tincture of opium; alcohol-based 10% opium by weight).

• 1600 – 1700: gradual increase in opium use until tobacco smoking concept exported from North America to China.

OPIOIDS THROUGH-OUT HISTORY

• 1729 : China - 28,000 lbs. imported; edict prohibited opium use.

• 1800 : China - 630,000 lbs. imported.

• 1803 : Morphine isolated from opium.

• 1832 : Codeine isolated from opium.

• 1838 : China - 5,600,000 lbs. imported.

• 1839 – 1842 : First Opium War

OPIOIDS THROUGH-OUT HISTORY

• California Gold Rush/Hypodermic needle/Civil War/Continental RR

• 1874 : Charles Wright synthesized heroin from morphine

• 1898 : Bayer marketed heroin as anti-tussive.

• 1908 : Pres. T. Roosevelt appoints Dr. Hamilton Wright as the first Opium Commissioner of the U.S.

• 1914 : Harrison Narcotic Act

• 1925 : International Opium Convention

OPIOIDS THROUGH-OUT HISTORY

• 1960’s: Designer drugs

• 1970 : Comprehensive Drug Abuse Prevention & Control Act

• 1973 : Identification of opioid binding sites/DEA established

• 1978 : Psychotropic Substances Act

• 1979 : China White in California

• 1986 : Controlled Substances Analogue Enforcement Act

• 1988 : China White in Pittsburgh

EPIDEMICS/PANDEMICS IN HISTORY

• Black Death : 1345 – 1355; 75,000,000 deaths

• Cholera : 1832 – 1849; 150,000 in U.S.

• Influenza : 1918 – 1920; 50,000,000 worldwide/500,000 in U.S.

• SARS : 800 deaths worldwide

• HIV : 14,000 deaths per year in U.S.

• Opioids : 40,000 deaths per year in U.S.

MULTIFACTORIAL ETIOLOGY

• New drugs.

• More drugs.

• More media.

• Different labeling.

• More regulations.

JCAHO AND THE MILLENNIALS

• Generation Me

• Pain is the 5th vital sign.

• Speak-up about your pain.

• Your pain deserves to be treated.

• No one should have to suffer any pain.

THE MEDIA

• 22 May 2016 : Pittsburgh Post-Gazette “Overdosed: How doctors wrote the script for an epidemic.”

• 14 September 2016 : Pittsburgh Post-Gazette “Emergency room narcotics prescribing would be reined in under legislation endorsed this week by Governor Tom Wolfe.”

• 20 September 2016 : Tribune-Review “Obama opens blitz on addiction crisis…..proclaiming…Prescription Opioid and Heroin Epidemic Awareness Week.”

• 27 October 2016 : Pittsburgh Post-Gazette “Four bills restricting prescribing and improving doctor education won final passage…”

DESIGNER DRUGS

• Psychedelics

• Dissociatives

• Piperazines

• Empathogens

• Stimulants

• Sedatives

• Synthetic Cannabinoids

• Androgens

• Peptides

• PDE-5 Inhibitors

• Nootropics

EMCDDA

• European Monitoring Centre for Drugs and Drug Addiction

• 2009…………………………..24 new drugs

• 2010…………………………..41 new drugs

• 2012…………………………..73 new drugs

• 2013…………………………..81 new drugs

DEFINITIONS

• An opiate is : any of the alkaloids naturally derived from the opium poppy (morphine, codeine, thebaine, and noscapine).

• An opioid is : any zenobiotic that is capable either of producing an opium-like effect or of binding to opioid receptors.

• Semisynthetic opioids (heroin or oxycodone) : created by chemical modification of an opiate.

• Synthetic opioids ( methadone or fentanyl) : a chemical, not derived from an opiate, that binds to an opioid receptor.

SYNTHETIC OPIOIDS

• Fentanyl

• Sufentanil

• Furanyl fentanyl

• Carfentanyl

• U47700 (Pink)

FENTANYL

• N-(1-(2-phenylethyl)-4- piperidinyl-N-phenylpropanamide.

• CAS #437-38-7

• 100 x more potent than morphine

• Duration of action 45 minutes.

• Developed 1960 (Paul Janssen)

FURANYL FENTANYL

• N-phenyl-N-[1-(2-phenylethyl)-4-piperidinyl]-2-furamide

• PubChem CID #13653606

• 5 x less potent than morphine.

• Duration of action 45 minutes.

CARFENTANIL

• Methyl-1-(2-phenylethyl)-4-(N-propanoylanilino)piperidine-4-carboxylate

• CAS #59708-52-0

• 10,000 x more potent than morphine.

• Developed 1974 by Janssen Pharmaceuticals.

• 2002 Moscow hostage rescue.

U47700

• 3,4-dichloro-N-[(1R,2R)-2-dimethylamino)cyclohexyl]-N-methylbenzamide

• CAS #82657-23-6

• 7.5 x more potent than morphine.

• Selective Kappa receptor agonist

• Developed by Upjohn in 1970’s

• Pink

URINE DRUG SCREENS

• Opiate assay is based on chemical structure of morphine.

• Heroin (diacetyl morphine) is metabolized to morphine.

• Methadone is not metabolized to anything that resembles morphine.

• Buprenorphine is not metabolized to anything that resembles morphine.

• Fentanyl is not metabolized to anything that resembles morphine.

RECEPTORS

Conventional

• μ (Mu)

• κ (Kappa)

• δ (Delta)

IUPHAR

• MOP

• KOP

• DOP

DEAD ROCK STARS

DEAD ROCK STAR #1

• The Title

• The Artist

• The Year of their Death

• Their Poison

DEAD ROCK STAR #2

• The Title

• The Artist

• The Year of their Death

• Their Poison

DEAD ROCK STARS

OPIOID OUTCOMES IN CLINICAL PRACTICE

DEAD

• Cardiac

• Brain• ? Organ Donation

ALIVE

• Vegetative from anoxic brain

• Recurrent sedation

• ARDS

• HIV/Hep C/Endocarditis

• Adulterants

• Movement disorders

• Endocrine effects

DETOX/REHAB

• Methadone

• Buprenorphine

• ROD/UROD

• Cold Turkey

OPIOID PRESCRIBING

Do

• Treat acute pain as needed.

• Advise patient that some pain is expected.

• Check PA PDMP

Do Not

• Use combination opioid with acetaminophen.

• Provide opioid because patient will complain to administration or State Medical Board.

• Prescribe in dose not exceeding 50 MME per day (10mg oxycodone every 4 hours while awake.

NALOXONE

NALOXONE

THE PENDULUM SWINGS

• God’s own medicine

• Ethical duty to treat pain

• Medicine for the individual

• No government intervention

• Life must be without physical pain

• Opiophobia

• No pain no gain

• Medicine for the public welfare

• Government regulation

• Life without physical pain is not a full life

WEBSITES

Erowid.org

DEA.gov

Clintox.org

ACMT.net

EMCDDA.europa.eu