OPIOID OVERDOSE STATISTICS
The overdose deaths involving opioids, including prescription medications, heroin, and synthetic opioids such as fentanyl, have steadily and dramatically increased over the last 2 decades. Drug overdose deaths spiked during the COVID-19 pandemic despite the increased attention and attempted regulation. Fentanyl is the main driver of drug overdose deaths and accounts for 80% of all opioid related fatalities. 12 Fentanyl is also currently responsible for the majority of illicit use complications in general. 13 Fentanyl is a short acting, but potent opioid and is widely used by providers for treatment of pain using multiple formulations. However, it is also
found in illegal, adulterated samples of illicit drugs in various concentrations, making overdose common. Studies estimate that over 150 people die per day from Fentanyl related overdoses. 14 This number of overdose deaths continues to increase primarily due to the presence of inexpensive production of synthetic opioids and psychostimulants such as methamphetamine. 15 Most recently, estimates from the Centers for Disease Control and Prevention show that more than 105,000 lives were lost to drug overdose in 2021 alone, an increase from 2020. 16, 17,18,19 Modeling studies predict overdose deaths to reach over half a million cases in the next decade. 20
PHYSIOLOGY
Opioid receptor stimulation can be achieved from both exogenous and endogenous sources. Exogenous opioids like morphine, heroin, and fentanyl are substances that are introduced into the body and will bind to the same receptors as the endogenous opioids, commonly referred to as endorphins. These opioid medications closely mimic the structure of natural endorphins that are released within the body and therefore produce a physiological effect of decreased pain perception. Endogenous stimulation of opiate receptors occurs naturally within the body via release of endorphins in response to multiple stimuli including pain, stress, exercise, eating, and sex. 21 The physiology of opioid pathways is well, but not completely, understood. Stimulation of these opiate receptors share multiple effects on the human body other than just pain control and can include sedation, nausea, euphoria, respiratory depression, pupillary miosis, cough suppression, constipation and pruritus. The intensity and duration of these effects vary with different formulations. Multiple types of endorphins with various subtypes have been discovered and act on opioid receptors that are located not only in the brain, but throughout the body. They are located peripherally in the carotid bodies and vagal receptors in the lungs and account for the respiratory depression, hypoxia and sometimes death related to opioid overdose. Constipation is very common and is induced through inhibition of acetylcholine decreasing motility and by decreasing chloride secretion, limiting passive movement of water into the gut. Histamine release is triggered through non- allergic mast cell activation resulting in pruritis, vasodilatation and occasionally hypotension. Hypotension can also be triggered by vagal nerve stimulation causing bradycardia. Other effects include SIADH, immune dysfunction, sleep and mood changes. 22 Nausea and vomiting are also very common side effects and occur in over one third of patients using opioids. 23 It has been observed that opioid induced nausea and vomiting related to the vestibule-ocular reflex can be reduced by limiting head movement. 24 It is also understood that secondary effects of opioids, through GABA secretion, modulate the release of
dopamine which has significant effects on these substances’ ability to positively reinforce its use. 22 This dopaminergic stimulation associated with opioid use is a major factor in the behavior exhibited in patients that suffer from Opioid Use Disorder (OUD). In fact, apart from the LSD- and mescaline-like hallucinogens, functional dopamine agonism is the single pharmacological property that all addictive drugs share. 25 Opioid stimulation of dopamine is part of a complex system of addiction within the brain's reward centers. Understanding of the physiology of addiction and OUD requires one to recognize the incredibly strong positive reinforcement exerted by these pathways. Studies in the 1950s demonstrated that rats that had electrical stimulation to the mesolimbic dopamine system would repeatedly cross a highly electrified grid that was painful in order to repeatedly stimulate the release of dopamine in the brain. Starving rats, in contrast, would not cross that same grid despite the presence of food in sight. 26 It is this behavior in response to dopamine that puts the sometimes-desperate actions of those patients suffering from OUD into perspective. In contrast to endogenous endorphins, which are quickly metabolized, exogenous use of agents that bind to opioid receptors have longer half-lives. Continued use of these drugs lead to down regulation of natural endorphins and up regulation of opiate receptors leading to increased pain sensitivity and dysphoria when those receptors are not activated. The primary analgesic effect of administered exogenous opioids proved useful in the treatment of painful conditions across many disciplines, but led to increased use of this type of medicine by many practitioners, which then led to unintended side effects and complications such as dependence. Many patients that become habituated to these drugs do not use the drugs recreationally or for pleasure, but use them increasingly to avoid pain and dysphoria related to withdrawal in an attempt to feel "normal."Recent initiatives have sought to better educate all practitioners on the effects of opioid medicines and to define strategies that are considered responsible and effective for patients. Multiple programs and processes have been created
Book Code: CT24CME
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