Opioids, Naloxone, Naltrexone

Opiates, primarily targeting the μ-opioid receptor, mediate effects such as analgesia, sedation, constipation, and respiratory depression. TThe activation of opiate receptors leads to the opening of K+ channels and the closure of voltage-gated (VG) Ca2+ channels. Specifically, the closure of presynaptic VG Ca2+ channels inhibits the release of several neurotransmitters, including glutamate, acetylcholine, norepinephrine, serotonin, and substance P. Key clinical opiates include fentanyl, morphine, and the weaker μ-opioid agonist, tramadol, which also modulates norepinephrine and serotonin. Loperamide and diphenoxylate serve as antidiarrheals, slowing stool transit in the GI tract, while codeine and dextromethorphan, which additionally antagonizes NMDA receptors, function as antitussives. Prolonged opiate use can cause side effects such as CNS depression, miosis, and respiratory depression, and may lead to tolerance and opiate-induced hyperalgesia. Withdrawal from opioids can manifest symptoms from rhinorrhea and yawning, to severe anxiety and diarrhea. To treat withdrawal, long-acting opioids like methadone and buprenorphine are used. However, neonates exposed to opioids in utero may present with neonatal abstinence syndrome. In cases of acute opioid toxicity, naloxone, a μ-opioid antagonist, proves invaluable in reversing the effects, though its administration can precipitate withdrawals. For managing opioid use disorder, a combination of buprenorphine/naloxone is favored. Another μ-opioid antagonist, naltrexone, aids in maintaining abstinence in heroin addicts, reducing cravings for alcohol and nicotine, and has been linked to promoting weight loss.