HAHAHAHAHAHAHAHAHHAHAHAHAHHAHAHAHAHAHHAHHAHAHAHHAHAHHAHAHAHAHAHAHAHAHAHHAHAHAHAHAHHAHAHAHAHAH
Buprenorphine, a potent, synthetic morphine analog with mixed opioid agonist-antagonist properties and a long half-life, is readily absorbed from sublingual mucosal tissues. The portion of the drug that is swallowed is almost completely metabolized by the liver, and only a small fraction can reach the systemic circulation when swallowed. Systemic bioavailability after sublingual buprenorphine is approximately 50% of that following intravenous administration. In several studies, sublingual buprenorphine (0.4 mg) was compared with conventional intramuscular morphine or meperidine and found to provide comparable and satisfactory analgesia.
Agonist-antagonist opioids are usually produced by alkylation of the piperidine nitrogen and addition of a three-carbon side chain such as a propyl, allyl, or methyl allyl to morphine. Buprenorphine is a partial agonist at the μ-receptor. The other compounds are μ-antagonists and full or partial agonists at the κ-receptors. Agonist-antagonist opioids are less prone (but not immune) to abuse because they cause less euphoria and are associated with less drug-seeking behavior and physical dependence.
Buprenorphine is a thebaine derivative, μ-receptor partial agonist, and similar in structure to morphine but approximately 33 times more potent. Whereas fentanyl dissociates rapidly from μ- receptors (half-life of 6.8 minutes), buprenorphine has a higher affinity and takes much longer to dissociate (half-life of 166 minutes). Its onset of action is slow, its peak effect may not occur until 3 hours, and its duration of effect is prolonged (>10 hours). The volume of distribution of buprenorphine is 2.8 L/kg and its clearance is 20 mL/kg/min. The metabolites of buprenorphine, buprenorphine-3-glucuronide and norbuprenorphine, are significantly less potent and have lower affinity for the μ-receptor.
The subjective effects (e.g., euphoria) of buprenorphine are similar to those of morphine. Buprenorphine produces respiratory depression with a ceiling after 0.15 to 1.2 mg in adults. Higher doses do not produce further respiratory depression and may actually result in increased ventilation (predominance of antagonistic actions).[478] Reversal with naloxone is limited by high affinity for and slow dissociation from the μ-opioid receptor of buprenorphine. [479] Buprenorphine has been successfully used for premedication (0.3 mg IM), as the analgesic component in balanced anesthesia (4.5 to 12 μg/kg), and for postoperative pain control (0.3 mg IM).[480] Buprenorphine, like the other agonist-antagonist compounds, is not acceptable as a sole anesthetic, and its receptor kinetic profile restricts its usefulness if other μ-agonists are used. Opioid withdrawal symptoms develop slowly (5 to 10 days) after buprenorphine is discontinued following long-term administration.