A theoretical model of activity:<unk>  at opioid receptor when taken sublingually (top) versus when injected intravenously (bottom).<unk>  as a partial agonist:<unk>  cannot fully activate the µ-opioid receptor even when the dose is escalated. This is demonstrated as a plateau in the concentration-response curve. Opioids like morphine (natural) or leu-enkephalin (endogenous in the body) produce a greater maximum response. Tramadol is a partial agonist with intermediate activity between<unk>  and full agonists. A full description of<unk>  with naloxone pharmacology can be found at https://www.youtube.com/watch?v=_y8DGjkP1so Mechanism of action<unk>  binds strongly to opioid receptors and acts as a pain-reducing medication in the central nervous system (CNS). It binds to the μ-opioid receptor with high affinity which produces the analgesic effects in the CNS. It is a partial μ-opioid receptor agonist and it is a weak κ-opioid receptor antagonist. As the dose of<unk>  increases, its analgesic effects reach a plateau, and then it starts to act like an antagonist. As a partial agonist,<unk>  binds and activates the opioid receptors, but has only partial efficacy at the receptor relative to a full agonist, even at maximal receptor occupancy. It is thus well-suited to treat opioid dependence, as it produces milder effects on the opioid receptor with lower dependence and habit-forming potential. Naloxone is a pure opioid antagonist that competes with opioid molecules in the CNS and prevents them from binding to the opioid receptors. Naloxone's binding affinity is highest for the μ-opioid receptor, then the δ-opioid receptor, and lowest for the κ-opioid receptor. Naloxone has poor bioavailability, and is rapidly inactivated following oral administration. When injected however, it exerts its full effects. Incorrectly attributed to the differing bioavailability between the two medications in this combination,<unk>  works as a deterrent against injected use: Not because of the physiological consequences caused by injecting Naloxone with<unk>  but instead, via psychological means. The mere thought of going into precipitated withdrawal is enough to keep users from injecting that first time. However, this propaganda ceases to affect users that have already tried injecting the combination due to the realization that it can be done successfully. That said, the principle behind its function as a deterrent is as follows: when taken sublingually as prescribed, the<unk>  effects at the opioid receptor dominate, while the naloxone effects are negligible due to the low oral absorption. However, when someone attempts to misuse the medication either via injection or inhalation, the naloxone is intended to act as an antagonist and either reduce the euphoric effects of the opioid or even precipitate withdrawal in those currently dependent on opioids. This helps reduce the potential for deviating from the prescriber's intended use relative to<unk> , although it does not eradicate it. One reason that naloxone might have limited efficacy as an abuse deterrent is that<unk>  binds more tightly to the mu-opioid receptor than naloxone. Pharmacokinetics There are small differences in the pharmacokinetics between different sublingual<unk>  products. These differences may require changes in dose when a person switches from taking one product to another. The<unk>  sublingual film (e.g. trade name Suboxone) achieves higher<unk>  maximum plasma concentrations (Cmax) and area under the curve (AUC, a measure of total drug exposure) than the original<unk>  sublingual tablets at equal doses. For example, at a<unk>  dose of 8 mg/2 mg, the<unk>  Cmax after a single dose of the original tablet formulation is around 3 ng/mL whereas that of the 8 mg/2 mg film formulation is around 3.55 ng/mL. The Zubsolv trade name sublingual tablets have higher<unk>  bioavailability than the original sublingual tablets, while the Bunavail trade name buccal films have the highest bioavailability. For example, a single dose of Bunavail 4.2 mg/0.7 mg achieves a Cmax around 3.41 ng/mL.<unk> <unk>  is metabolized by the liver, primarily via the cytochrome P450 (CYP) isozyme called CYP3A4, into norbuprenorphine. The glucuronidation of<unk>  is primarily carried out by the UDP-glucuronosyltransferases (UGTs) UGT1A1 and UGT2B7, while norbuprenorphine is glucuronidated by UGT1A1 and UGT1A3. These glucuronides are then eliminated mainly through excretion into bile. The elimination half-life of<unk>  is 20 to 73 hours (mean 37 hours). Due to the mainly hepatic elimination, there is no risk of accumulation in people with kidney problems. Naloxone Naloxone is extensively inactivated by first-pass metabolism in the liver, meaning that use of<unk>  as prescribed should not lead to active naloxone in the blood (which, as an opioid antagonist, would reverse the effect of<unk>  or other opioids).
Buprenorphine/naloxone
Oxycodone/naloxone
Buprenorphine/naltrexone
Fentanyl/fluanisone
Buprenorphine/samidorphan
Dextromethorphan/quinidine
Naloxone
Nalorphine dinicotinate