Acute opioid intoxication in adults
- Andrew Stolbach, MD, MPH, FAACT, FACMT, FACEP
Andrew Stolbach, MD, MPH, FAACT, FACMT, FACEP
- Associate Professor of Emergency Medicine
- Johns Hopkins University
- Robert S Hoffman, MD
Robert S Hoffman, MD
- Professor of Emergency Medicine
- Director, Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine
- New York University School of Medicine
- Section Editor
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Deputy Editor
- Jonathan Grayzel, MD, FAAEM
Jonathan Grayzel, MD, FAAEM
- Senior Deputy Editor — UpToDate
- Deputy Editor — Emergency Medicine (Adult and Pediatric)
- Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Assistant Professor of Emergency Medicine
- University of Massachusetts Medical School
Opiates extracted from the poppy plant (Papaver somniferum) have been used recreationally and medicinally for millennia. Opiates belong to the larger class of drugs, the opioids, which include synthetic and semi-synthetic drugs, as well. Opioid abuse is a worldwide problem and deaths from opioid overdose are numerous and increasing [1-5].
This topic review will discuss the mechanisms, clinical manifestations, and management of acute opioid toxicity. A summary table to facilitate emergent management is provided (table 1). Issues related to opioid withdrawal, chronic opioid abuse, and general management of the poisoned patient are found elsewhere. (See "Opioid withdrawal in the emergency setting" and "Pharmacotherapy for opioid use disorder" and "Opioid use disorder: Epidemiology, pharmacology, clinical manifestations, course, screening, assessment, and diagnosis" and "General approach to drug poisoning in adults".)
PHARMACOLOGY AND CELLULAR TOXICOLOGY
The opioid pharmaceuticals are analogous to the three families of endogenous opioid peptides: enkephalins, endorphins, and dynorphin. The most recent classification scheme identifies three major classes of opioid receptor, with several minor classes . Within each receptor class there are distinct subtypes. Each subtype produces a variety of distinct clinical effects, although there is some overlap (table 2). For most clinicians, the nomenclature derived from the Greek alphabet is more familiar, although the International Union of Pharmacology (IUPHAR) Committee on Receptor Nomenclature has recommended a change from the original Greek system to make opioid receptor names more consistent with other neurotransmitter systems .
The opioid receptors are distinct in their locations and clinical effects, but they are structurally similar (table 2). Each consists of seven transmembrane segments, with amino acid and carboxy termini. Although the opioid receptors are all coupled to G proteins, they use a variety of signal transduction mechanisms . These include reducing the capacity of adenylate cyclase to produce cAMP, closing calcium channels that reduce the signal to release neurotransmitters, or opening potassium channels to hyperpolarize the cell . The net result of these mechanisms is to modulate the release of neurotransmitters.
Opioid receptors exist throughout the central and peripheral nervous system and are linked to a variety of neurotransmitters, which explains the diversity of their clinical effects. The analgesic effects of opioids result from inhibition of nociceptive information at multiple points of its transmission from the peripheral nerve to the spinal cord to the brain. Euphoria results from increased dopamine released in the mesolimbic system . Anxiolysis results from effects on noradrenergic neurons in the locus ceruleus .
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- PHARMACOLOGY AND CELLULAR TOXICOLOGY
- CLINICAL FEATURES OF OVERDOSE
- Physical examination
- Toxicities of specific agents
- DIFFERENTIAL DIAGNOSIS
- LABORATORY EVALUATION AND ANCILLARY STUDIES
- Laboratory evaluation
- Basic measures and antidotal therapy
- Gastrointestinal decontamination
- Extracorporeal removal
- Body packing and body stuffing
- Lung injury and ARDS
- TREATMENT OF TOXICITY OF SPECIFIC OPIOIDS
- Fentanyl and fentanyl analogs
- Buprenorphine and naloxone
- Opioid adulterants, including krokodil
- HARM REDUCTION AND TAKE-HOME NALOXONE
- ADDITIONAL RESOURCES
- SUMMARY AND RECOMMENDATIONS
- Pharmacology and presentation