Opioid Use Disorder __________________________________________________________________________
Nalbuphine Nalbuphine is an agonist-antagonist opioid related to naloxone and oxymorphone, with a spectrum of effects that qualitatively resembles that of pentazocine but with a lower potential to produce dysphoric side effects. Although doses of 10 mg or less produce few side effects, much higher doses (70 mg) can produce psychotomimetic side effects such as dysphoria, racing thoughts, and distorted body image. Prolonged administra- tion of nalbuphine can produce physical dependence and withdrawal [9]. Butorphanol Butorphanol is a morphinan congener with a profile of actions similar to those of pentazocine. It is generally more suitable for the relief of acute pain than chronic pain. Major side effects include drowsiness, weakness, sweating, feelings of floating, and nausea. Although the incidence of psychotomimetic side effects is lower than that with equianalgesic doses of pentazocine, they are qualitatively similar. Physical dependence to butorphanol can develop from regular use [9; 55]. Buprenorphine Buprenorphine was initially suggested in 1978 as an alternative oral opioid substitution therapy for opioid addicts. Buprenor- phine and methadone are the two most widely used and effec- tive pharmacotherapies for opioid use disorder, and both have regulatory approval in the United States for this indication [68]. Buprenorphine is a semi-synthetic opioid derivative made from thebaine, one of the naturally occurring alkaloids in opium [69]. Buprenorphine, sold as Buprenex, Subutex, Belbuca, or Sublocade, is a long-acting partial opioid agonist that is classi- fied as a Schedule III narcotic, in contrast to methadone and LAAM, which are Schedule II [55; 56; 70]. Buprenorphine has a very low oral bioavailability due to substantial intestinal and hepatic metabolism. The sublingual formulation used to treat opioid dependence is well-absorbed and produces opioid agonistic effects comparable to subcuta- neous administration. Maximum plasma level is achieved 70 to 90 minutes after sublingual administration, and absolute bioavailability is 35% to 50% [69]. Following absorption, buprenorphine initially accumulates in the liver, kidneys, muscular tissue, and fatty tissue. It is released from fatty tissue when the plasma level drops and is then available at the opioid receptor. The slow dissociation kinetics explains the prolonged period of effectiveness. Buprenorphine is metabolized through the hepatic cytochrome P450 pathway. Approximately 80% is eliminated through binary excretion of the glucuronidated metabolites and 20% via the urinary route [69]. The minimum daily dose needed to suppress opioid use is about 4 mg. Larger doses of buprenorphine (32 mg) result less in an increase in therapeutic effect but more in an extension of the effect, which can last for up to 48 hours [69].
• It is recommended to reserve ER/LA opioid pain medicines for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate. • A warning about opioid-induced hyperalgesia (OIH), including information on differentiating OIH symp- toms from those of opioid tolerance and withdrawal. MIXED AGONISTS/ANTAGONISTS Discovery of an opioid analgesic with the efficacy but not the side effects or abuse potential of mu-agonists has been the ulti- mate goal of analgesic research for the past 60 years [25]. Mixed agonist-antagonist compounds have been developed with the hope that they would have less addictive potential and create less respiratory depression than morphine and related drugs. However, achieving the same degree of analgesia produces a similar magnitude of side effects, and a “ceiling effect,” limiting the amount of analgesia attainable, is often seen with these drugs. Also, mixed agonist-antagonist drugs (e.g., pentazocine) can produce side effects not often seen with pure agonists, including severe, irreversible psychotomimetic effects [9]. Drugs such as nalbuphine and butorphanol are competitive mu-receptor antagonists, with their kappa receptor agonist action mediating the analgesic effect. Pentazocine qualitatively resembles these drugs but is a weaker mu-receptor antagonist or partial agonist while retaining its kappa-agonist activity. Buprenorphine is a partial mu-receptor agonist [9]. Pentazocine Pentazocine was developed in an effort to synthesize an effec- tive analgesic with little or no abuse potential. With agonistic actions and weak opioid antagonistic activity, the pattern of central nervous system effects is similar to that of morphine- like opioids, including analgesia, sedation, and respiratory depression. Dysphoric and psychotomimetic effects can be precipitated by higher doses (60 to 90 mg) [9]. In the 1970s and early 1980s, pentazocine (Talwin) was com- bined with the crushed, blue-colored antihistamine tablet tripelennamine and used intravenously, known as “Ts and Blues.” Factors contributing to its widespread abuse included placement outside Schedule II and the erroneous belief that the drug was not abusable. Pentazocine was also widely abused by physicians because it could be prescribed in large quantities outside the stringent Schedule II monitoring system. At one point, pentazocine abuse became so prevalent that the manu- facturer contemplated removing the drug from the market. Pentazocine was ultimately reformulated by the inclusion of the opioid antagonist naloxone. Similar to buprenorphine formulations containing naltrexone, when this formulation is taken as directed, the user experiences only the pentazocine effect because of poor oral naloxone absorption. However, if the tablet is dissolved and injected, the naloxone blocks the opioid effects of the pentazocine and precipitates acute opioid withdrawal [1].
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MDRI2026
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