not completely, understood. Stimulation of these opiate receptors shares 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 nonallergic mast cell activation resulting in pruritus, vasodilatation, and occasionally hypotension. Hypotension can also be triggered by vagal nerve stimulation causing bradycardia. Other effects include SIADH , immune dysfunction, and sleep and mood changes. 75 Nausea and vomiting are also very common side effects and occur in over one third of patients using opioids. 76 It has been observed that opioid induced nausea and vomiting related to the vestibule-ocular reflex can be reduced by limiting head movement. 75 It is also understood that secondary effects of opioids, through GABA secretion, modulate the release of 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 two 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. 65 Fentanyl is also currently responsible for the majority of illicit use complications in general. 66 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. Risk factors in opioid use disorders In general, individuals take opioids and other intoxicating substances for a variety of reasons, including (1) pleasure; (2) an escape from social anxiety, stress, and depression; (3) to increase performance; and (4) curiosity and social pressure. No single factor determines whether an individual becomes addicted to drugs, and factors can be biological or environmental. 71 Biological influences in persons with OUD include genetics, gender, and mental health disorders, while environmental influences include chaotic home situations, parental use and attitudes, peer influences, community attitudes, and low academic achievement.
dopamine, which has significant effects on these substances’ ability to positively reinforce their use. 77 This dopaminergic stimulation associated with opioid use is a major factor in the behavior exhibited in patients that suffer from OUD. In fact, apart from the LSD- and mescaline-like hallucinogens, functional dopamine agonism is the single pharmacological property that all addictive drugs share. 78 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. 79 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 leads 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. Studies estimate that over 150 people die per day from fentanyl-related overdoses. 67 This number of overdose deaths continues to increase primarily due to the presence of inexpensive production of synthetic opioids and psychostimulants such as methamphetamine. 68 The number of drug overdose deaths increased by nearly 5% from 2018 to 2019 and has quadrupled since 1999. 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. 69 Opioids are the most commonly associated substance in this statistic, and future modeling studies predict overdose deaths to reach over half a million cases in the next decade. 70 Risk factors for substance abuse include (1) aggressive behavior in childhood, (2) lack of parental supervision, (3) peer refusal skills, (4) drug experimentation, (5) availability of drugs at school, and (6) community poverty. Protective factors reduce an individual’s risk of substance use and include (1) self-efficacy affected by personal and home situations, (2) parental monitoring and support, (3) positive relationships, (4) extracurricular activities, (5) antidrug policies at school, and (6) neighborhood resources. 72 One of the most important changes during development in adolescence is the maturing prefrontal cortex, which is responsible for assessment
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Book Code: MI24CMEB
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