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Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
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Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
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Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
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A call for compassionate opioid overdose response.

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High-dose opioid overdose reversal drugs risk withdrawal. Experts call for community involvement, standard naloxone doses, and compassionate care to prioritize breathing over withdrawal.

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Area of Science:

  • Public Health
  • Pharmacology
  • Harm Reduction

Background:

  • High-dose and long-acting opioid overdose reversal drugs pose an increased risk of precipitating withdrawal in opioid-dependent individuals.
  • Recent product introductions in the US have raised international concerns regarding the potential for severe withdrawal symptoms.
  • Existing evidence from global naloxone distribution programs supports the use of standard doses that restore breathing without inducing withdrawal.

Purpose of the Study:

  • To address concerns regarding high-dose and long-acting opioid antagonists and their impact on opioid withdrawal.
  • To advocate for a patient-centered approach in the development and distribution of overdose reversal products.
  • To provide recommendations for regulatory agencies, pharmaceutical manufacturers, and harm reduction programs.

Main Methods:

  • A panel of harm reduction experts convened at the Compassionate Overdose Response Summit & Naloxone Dosing Meeting (March 18-19, 2024).
  • The panel issued a call to action based on expert consensus and existing evidence.
  • Recommendations focused on community involvement, risk communication, appropriate dosing, and compassionate care.

Main Results:

  • Experts recommend direct involvement of people who use drugs in product research, development, selection, and distribution.
  • Regulatory agencies and manufacturers should clearly communicate withdrawal risks associated with higher-dose, longer-acting antagonists.
  • Recommended take-home naloxone kits include at least two doses of 0.4 mg intramuscular (IM) or ≤4 mg intranasal (IN) products.
  • High-dose and long-acting opioid antagonists are deemed unsuitable for acute overdose response at this time.
  • Overdose response training should prioritize restoring breathing, avoiding withdrawal, and providing compassionate support.

Conclusions:

  • Standard-dose naloxone products are crucial for effective and compassionate overdose response.
  • Government agencies should fund harm reduction programs to ensure widespread availability of standard-dose naloxone.
  • A compassionate approach, emphasizing breathing restoration and minimizing withdrawal, should guide all aspects of overdose response and care.