_________________________________________________________________________ Opioid Use Disorder
in 2006, declined to 0.9 in 2018, and was then stable through 2021 [37]. Most methadone fatalities occur when the drug is prescribed for pain rather than for addiction treatment [60]. RISK FACTORS Heroin purity has only a moderate relationship to heroin- related fatalities, and despite the increasing incidence of heroin ingestion by smoking, almost all overdose deaths remain the result of injection. In fatal overdoses, instantaneous death is uncommon, indicating that there is time to intervene in the majority of cases. However, public responsiveness to overdoses is often poor, with the most common reason for delayed response being fear of police involvement [99]. The time following release from prison has also been identified as a very-high-risk period for both fatal and nonfatal overdose [99]. Methadone overdose decedents are more likely than other pharmaceutical opioid abusers to not have had a prescription for the overdose drug. Although they are also significantly more likely to be male, the gap between men and women is closing [100; 101]. Since 1999, the percentage increase in overdose deaths among women increased 400%, compared with 265% in men [100]. Tolerance in Overdose Variation has been found in the acquisition of tolerance to different opioid effects, including respiratory depression [34]. The role of tolerance in heroin overdose is suggested by the rigors of the heroin lifestyle, which often results in a reduction in use after a decade or more of use. Often, heroin addicts increase the use of other drugs, such as alcohol, to compensate for reduced heroin use. Both of these factors increase the risk for overdose. Polysubstance Use Polysubstance use in cases of fatal heroin overdose is so fre- quent that polydrug toxicity is often a better description of the cause of death. The primary drugs associated with fatal and nonfatal overdose are alcohol, benzodiazepines, and TCAs. The risk of nonfatal heroin overdose is increased significantly by TCA use but not by selective serotonin reuptake inhibitor (SSRI) use [16]. Alcohol and benzodiazepines are relatively weak respiratory depressants but can act synergistically with opioid agonists to produce substantial respiratory depression. Stimulants act as functional or physiologic opioid antagonists and may therefore minimize the respiratory depressant effects of opioids [51]. SYMPTOMS In the case of opioid overdose, symptoms include mental clouding, stupor or coma, miotic pupils, bradypnea, dimin- ished response to painful stimuli, and mottled, cooled skin. Respiratory depression is the most feared acute adverse effect. Direct suppression of the brain stem respiratory center leads to bradypnea, shallow respirations, and a significant overall
reduction of tidal volume. Death from opioid overdose is almost always caused by respiratory depression [8; 102]. Sequelae of nonfatal overdose include [34]: • Pulmonary conditions, most frequently edema • Pneumonia • Cardiac complications such as arrhythmia, acute cardio- myopathy, and hemoglobinemia • Rhabdomyolysis (disintegration or dissolution of muscle cells leading to myoglobinuria) • Neurologic damage through prolonged hypoxia OPIOID WITHDRAWAL A withdrawal syndrome can be precipitated in humans after even a single dose of morphine. Physical dependence to opi- oids is assessed by observing the emergence of a withdrawal syndrome following discontinuation of opioid administration or through the administration of a competitive opioid antago- nist, such as naloxone [103]. Signs and symptoms of opioid withdrawal include [87; 104]: • Dilated pupils • Rhinorrhea • Epiphora/lacrimation • Piloerection • Nausea
• Vomiting • Diarrhea • Yawning • Muscle cramps • Restlessness • Elevated vital signs
Although the neurophysiology underlying opioid withdrawal is incompletely understood, several neurotransmitter systems are believed to play a role, including dopaminergic, cholinergic, noradrenergic, and glutamatergic systems [103]. The extended amygdala is robustly implicated in affective signs of withdrawal from chronic exposure to opioids. Less is known about the cellular mechanisms underlying acute dependence [82]. The progressive escalation of withdrawal severity that occurs across repeated acute opioid exposure separated by prolonged inter- vals suggests the involvement of long-term cellular plasticity in acute dependence [82]. The involvement of central mecha- nisms of the endothelin system in opioid withdrawal is also being investigated [105; 106]. There are a number of useful opioid withdrawal scales that can assist the clinician’s evaluation of patients by identifying and quantitating the severity of opioid withdrawal symp- toms. These include the Objective Opioid Withdrawal Scale (OOWS), the Subjective Opioid Withdrawal Scale (SOWS),
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MDRI2026
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