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.
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