Fentanyl as Sentinel: The Deadly Threat of Illegal Synthetic and Counterfeit Drugs

Fentanyl as Sentinel: The Deadly Threat of Illegal Synthetic and Counterfeit Drugs

Publication date: Sep 05, 2019

Over several decades, NRC researchers synthesized many new analgesic drugs, including some that are still in use today, but they never succeeded in finding one that could meet the elusive goal. REF By the end of the 20th century, synthetic and semisynthetic opioids like oxycodone, methadone, and hydrocodone dominated a newly emergent medical specialty called pain management.

In 1999, the Veteran’s Health Administration, the largest government-run health care system in the U. S., adopted the campaign’s mantra that pain is every patient’s -Fifth Vital Sign” requiring measurement and treatment, when and if necessary, at every encounter. REF While all morphine and morphine substitute chemicals produce analgesia and brain reward, prolonged use may lead to analgesic tolerance in patients treated for pain and to compulsive intake by opioid addicts. REF Long-term use also may produce physical dependence, a condition manifested by somatic withdrawal symptoms in the absence of the drug. REF Withdrawal symptoms may include pain, insomnia, and diarrhea, which are, in effect, a reversal of the drug’s therapeutic effects.

Unlike tolerance or physical dependence, both of which typically respond well to medical management, a SUD is a life-threatening chronic disease characterized by compulsive use of psychoactive substances despite their harm. REF Until the 1980s, the use of opioids for treating chronic pain was reserved mostly for treating malignant pain and providing end-of-life care for patients whose physical dependence on the medication was not a relevant risk factor.

For several decades or more after World War II, there was growing demand in Europe and the United States for improved analgesics and anesthesia agents, the latter for use in modern surgical procedures for which ether and morphine-based drugs were unsuited.

In 1963, they synthesized fentanyl, a drug they estimated could have 100 times the potency of morphine. REF In 1961, Dr. Paul carried out a merger of his company with Johnson & Johnson (J&J), the American health care giant. REF Under the able supervision of Dr. Paul, the new J&J division, called Janssen Pharmaceutica L. P., continued to develop a variety of new drugs.

Committed to helping chronic pain patients, Dr. Paul and his J&J colleagues searched for a safe way to make fentanyl available as an outpatient drug.

In the 1970s, astronauts on their voyages to Skylab wore experimental scopolamine skin patches to address motion sickness. REF Dr. Paul and his J&J colleagues investigated this novel drug delivery system developed by the Alza CorporationREF under contract with the National Aeronautics and Space Administration. REF In 1990, the U. S. Food and Drug Administration (FDA) approved Janssen Pharmaceutica’s New Drug Application for Duragesic(R), the world’s first extended-release fentanyl transdermal drug delivery system for treating moderate to severe pain. REF Duragesic was manufactured by the Alza Corporation for Janssen Pharmaceuticals, Inc. REF The Duragesic fentanyl patch contained enough fentanyl to provide up to 72 hours of steady and measured dosing.

Its gelled formulation appeared to inhibit its misuse by people with substance use disorders. REF Unable to identify or safely isolate and measure the fentanyl in the gelled formulation, would-be misusers risked sudden overdose death if they exuded and consumed or injected the high-dose contents of the patch. REF This risk and the knowledge of it that was spread on the Internet via underground drug fora might have kept the instances of Duragesic abuse very low for many years. REF This, however, would change when generic solid matrix formulations were approved in 2005.

Fentanyl was the only truly new analgesic drug product approved for outpatient use during this period.

Concepts Keywords
Abstinence Web federal indictment
Addiction Analgesic drug product
Alkaloid Pain management
Analgesia Pharmaceutical fentanyl
Analgesic Production transportation costs
Analgesics Transportation hubs
Analog Availability pharmaceutical grade
Anesthesia Chemical lure abusers
Anesthetic Nations chemical drug
Bayer Pharmaceutical firms
Belgian Pharmaceutical products
Blood Brain Barrier Pharmaceutical heroin
Brain Drug chemical suppliers
Breakthrough Pain Web REFWhat
Care System Physical dependence condition
Chemist Law enforcement authorities
Chronic Pain Pharmaceuticals
Cocaine Active pharmaceutical ingredient
Codeine Pharmaceutical grade fentanyl
Congress Pain management
Cough Suppressant Chemotherapy
Cross Drug delivery system
Demon Powerful cough
Derivative Unintentional overdoses injuries
Detritus Epidemics
Diacetylmorphine Acute breakthrough pain
Diarrhea Drug addiction
Division Somatic withdrawal symptoms
Drug Delivery Chronic pain
Drug Overdose Epidemic late 1960s
Duragesic Injury
Elberfeld Pain insomnia diarrhea
Epidemic Fentanyl
Ether Synthetic opioids
Europe Piperidines
Extended Release Anilides
FDA Euphoriants
Fentanyl RTT
Folk Politics by country
Germany Opioids
Heroin Law by country
Hydrocodone Heroin
Insomnia Chemotherapy
Janssen Pharmaceutica Drug delivery system
Janssen Pharmaceuticals API
Lipophilic Oxycodone
Malignant
Mantra
Matrix
Medicinal Drug
Meperidine
Methadone
Milligram
Molecule
Morphine
Motion Sickness
Opioid
Opioids
Opium
Overdose
Overdose Deaths
Oxycodone
Pain
Pain Management
Painkiller
Painkillers
Patient Advocacy
Paul Janssen
Pethidine
Pharmaceutical
Pharmaceutical Company
Pharmaceutical Industry
Pharmaceuticals
Pharmacology
Physical Dependence
Piperidine
Pneumonia
Poppy
Prehistoric
Psychic
Psychoactive
Psychoactive Substances
Respiration
Ring
Risk Factor
Scopolamine
Semisynthetic
Skylab
Somatic
Statute
Sublingual
Substitute
Transdermal Drug Delivery
Transmucosal
Tuberculosis
Veterans Administration
War
Withdrawal Symptoms

Semantics

Type Source Name
gene UNIPROT NR4A2
gene UNIPROT LITAF
gene UNIPROT BPIFA4P
drug DRUGBANK Alpha-1-proteinase inhibitor
gene UNIPROT TNFSF14
disease MESH lifestyle
drug DRUGBANK Alprazolam
disease MESH drug abusers
drug DRUGBANK Lysergic acid diethylamide
disease MESH opiate addiction
disease MESH risk factor
disease MESH substance use disorder
disease MESH chronic disease
disease MESH insomnia
disease MESH withdrawal symptoms
disease DOID analgesia
disease MESH chronic pain
drug DRUGBANK Hydrocodone
drug DRUGBANK Methadone
drug DRUGBANK Oxycodone
drug DRUGBANK Cocaine
disease MESH habit
gene UNIPROT SERPINA3
gene UNIPROT FHL5
drug DRUGBANK Codeine
drug DRUGBANK Carfentanil
gene UNIPROT BAD
gene UNIPROT DNASE1L3
gene UNIPROT TNFRSF19
drug DRUGBANK Metamfetamine
drug DRUGBANK Medical Cannabis
drug DRUGBANK Ethanol
gene UNIPROT MMP12
gene UNIPROT AICDA
gene UNIPROT MME
gene UNIPROT NR4A3
disease DOID cancer
disease MESH cancer
gene UNIPROT RET
gene UNIPROT PDC
gene UNIPROT SELL
disease MESH communities
drug DRUGBANK Tropicamide
gene UNIPROT GRASP
disease MESH cause of death
disease DOID pneumonia
disease MESH pneumonia
pathway BSID Tuberculosis
disease DOID tuberculosis
disease MESH tuberculosis
disease DOID diarrhea
drug DRUGBANK Morphine
drug DRUGBANK Opium
drug DRUGBANK Nonoxynol-9
drug DRUGBANK Diamorphine
gene UNIPROT EHD1
drug DRUGBANK Fentanyl
disease MESH development
drug DRUGBANK Spinosad
disease MESH death
pathway BSID Release
disease DOID motion sickness
disease MESH motion sickness
drug DRUGBANK Scopolamine
gene UNIPROT LARGE1
drug DRUGBANK Methionine
gene UNIPROT SLTM
gene UNIPROT MET
drug DRUGBANK Meperidine
gene UNIPROT ARSK
gene UNIPROT DBF4
drug DRUGBANK Gold
gene UNIPROT CFLAR
gene UNIPROT SET
gene UNIPROT ALG3

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