Pharmacology
Summary
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.
Lesson Outline
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FAQs
The μ-opioid receptors are crucial in mediating both therapeutic and adverse effects of opioids, encompassing analgesia, sedation, constipation, and respiratory depression. When opioids bind to these receptors, they instigate the opening of K+ channels and inhibit voltage-gated calcium (VG Ca2+) channels. Inhibiting presynaptic VG Ca2+ channels in turn restrains the release of various neurotransmitters, including glutamate, acetylcholine, norepinephrine, serotonin, and substance P.
Antidiarrheal opioids, like loperamide and diphenoxylate, exert their effects through interaction with the μ-opioid receptors in the gastrointestinal (GI) tract. Their attachment to these receptors decelerates stool transit, aiding in diarrhea management. In particular, loperamide amplifies colonic phasic segmentation, prolonging stool transit time.
Opioid withdrawal is marked by a spectrum of symptoms: rhinorrhea, lacrimation, yawning, hyperventilation, hyperthermia, muscle discomfort, vomiting, diarrhea, and anxiety. To manage these withdrawal manifestations, long-acting opioids like methadone and buprenorphine are utilized, given their efficacy in diminishing withdrawal symptoms. Buprenorphine/nalaxone are also employed in sustained treatment protocols for opioid use disorder.
Naloxone acts as a μ-opioid antagonist, primarily administered to reverse opioid toxicity. By obstructing μ-opioid receptor activity, naloxone swiftly alleviates central nervous and respiratory system depressions that accompany opioid overdose. However, naloxone can induce withdrawals in individuals with chronic opioid use.
Naltrexone, a μ-opioid antagonist distinct from naloxone, serves a primary role in aiding opioid-dependent individuals to maintain abstinence. Additionally, naltrexone offers promise in curbing alcohol and nicotine cravings. In recent times, its beneficial effects on weight reduction have gained attention.
