Opioids Analgesics and Antagonists
Sahab Uddin, Rashid Mamunur in Advances in Neuropharmacology, 2020
A drug that dampens the biological activity by blocking some or all the subtypes of opioid receptor(s) is referred as opioid antagonists. Majorly, they are utilized to treat acute opioid overdose management, addiction treatment, and for the management of that patient population which cannot obtain adequate analgesia from opioids (e.g., Crohn’s disease, fibromyalgia, sickle cell anaemia, and neuropathy etc.). The most widely studied opioid antagonists are naloxone and naltrexone, which have higher affinity toward the receptors than agonists, but do not activate them. They effectively block the receptor, preventing the body from responding to exogenously administered opioids like morphine, heroin, meperidine, endorphins, and so on (Leavitt, 2009). These drugs have higher affinity for μ receptors in comparison to others and can pass through membranes (including blood–brain barrier) easily as; they have similar structure and equivalent lipophilicity. As shown in Figure 19.3, the evolution of opioid antagonists is also based on the morphine core structure.
Substance Use Disorders
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
MOUD should be continued throughout labor and delivery as it is not part of the labor analgesia. Similarly, complaints of pain should be taken seriously and not assumed to be drug seeking behavior. Opioid antagonists or agonist-antagonists can precipitate acute withdrawal [107]. Examples of these drugs are Nubain®, Talwin®, Stadol®, and Narcan®. If any of these drugs are accidentally given, withdrawal can also be reversed with any opioid [107]. Regional anesthesia is safe. However, hypotension may occur more frequently because of concomitant malnutrition and/or liver disease. If general anesthesia becomes necessary, poor dentition, airway burns, chronic lung disease, and decreased gastric emptying may result in airway compromise [12]. Peripheral intravenous access can be difficult in chronic intravenous drug abusers.
The opioid-tolerant patient, including those with a substance abuse disorder
Pamela E Macintyre, Suellen M Walker, David J Rowbotham in Clinical Pain Management, 2008
In animal models, very low doses of opioid antagonists attenuate excitatory but not inhibitory effects of morphine, thereby reducing OIH155 and preventing the development of morphine-induced tolerance.156 Clinical studies in both adults and children demonstrate that low-dose naloxone (for example, 0.25 µg/kg/hour by continuous intravenous infusion) reduces postoperative opioid side effects, such as pruritus and nausea, without compromising analgesia.157, 158[II] Compared with a higher-dose infusion or placebo, a continuous infusion of 0.25 µg/kg/hour reduces opioid requirements.158[II] The effect of opioid antagonists in opioid-tolerant patients has not been explored. However, conceivably the quality of analgesia might be improved.
Increasing access to medications for opioid use disorder: Policy analysis and proposals
Published in Journal of Addictive Diseases, 2021
James R. Latronica
Methadone is a full agonist opioid, which means that it works similarly to other opioids, but its decreased potency improves its safety profile. Methadone, originally approved for treatment of OUD in 1972, must be prescribed from a federally licensed Opioid Treatment Program (OTP)—as opposed to an outpatient office setting—and has a long-established track record of efficacy, safety, and low cost. Buprenorphine, approved for treatment of OUD in 2002, is a partial agonist opioid, which means that its effect on receptors in the brain is notably different than full agonist opioids, and because of its stronger receptor binding affinity compared to heroin, it acts as a protectant against overdose should a patient relapse. Buprenorphine can be prescribed in an office-based setting (as opposed to an OTP) if a provider completes an additional training course to receive their DATA 2000 waiver, which augments the provider’s DEA license. Naltrexone is an opioid antagonist which means that it blocks or removes opioid molecules in the brain’s receptors. Naltrexone binds to the brain’s opioid receptors, but does not activate them. Thus, it has a protective function, but its effect on stopping cravings—the nidus of the addiction cycle—is more effective than placebo, but not as robust.
Implementation of a collaborative model for opioid overdose prevention on campus
Published in Journal of American College Health, 2020
Lucas G. Hill, Lori K. Holleran Steiker, Lubna Mazin, Mark L. Kinzly
Ingesting opioids (eg heroin, oxycodone) may result in respiratory depression, a potentially fatal condition in which the brain and other vital organs do not receive sufficient oxygen to sustain life.8 Naloxone, an opioid antagonist, can rapidly reverse these effects when it is administered to an overdose victim. Community-based distribution of naloxone to laypersons, such as people who use drugs and their friends and family members, resulted in more than 26,000 lives saved from 1996–2014.9 Recognizing this, all 50 U.S. states and the District of Columbia have enacted legislation to expand access to naloxone.10 These laws typically provide liability protection to overdose responders and enable naloxone purchasing directly from pharmacists under a prescriber’s standing order. In at least 15 states, including Texas, they also authorize any person to possess naloxone without a prescription. This unique legal status facilitates making naloxone available for emergency access by staff and visitors to address suspected overdoses on campus, similar to the approach employed for fire extinguishers and automated external defibrillators. It also removes barriers to allowing students, faculty, and staff to distribute naloxone directly to students.
A retrospective cohort study of mortality rates in patients with an opioid use disorder treated with implant naltrexone, oral methadone or sublingual buprenorphine
Published in The American Journal of Drug and Alcohol Abuse, 2019
Erin Kelty, David Joyce, Gary Hulse
Naltrexone is also registered for the treatment of opioid use disorders. In contrast to methadone and buprenorphine, naltrexone is a pure opioid antagonist. The use of oral naltrexone has struggled clinically, with a lack of patient adherence with the once daily formulation reducing clinical efficacy. Additionally, patients who cease oral naltrexone treatment are reported to face an early increase in mortality, predominately from opioid poisoning (8,18). To sustain adherence with treatment, several longer acting preparations have been developed. One such preparation, a subcutaneous implant, provides therapeutic naltrexone blood levels for up to 188 days following a single treatment (19,20). The use of this implant preparation does not appear to be associated with periods of increase mortality following the treatment period, presumably due to slowly tapering release profile (18). While crude mortality rates in patients with an opioid use disorder treated with this implant have been comparable to reported rates in methadone- and buprenorphine-treated patients (18,21,22), direct comparisons of mortality have not yet been carried out (23). In this study, mortality in patients with an opioid use disorder treated with implant naltrexone was compared to patients treated with methadone or buprenorphine.