Nalbuphine: Difference between revisions

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'''Nalbuphine''', sold under the brand names '''Nubain''' among others, is an [[opioid]] [[analgesic]] which is used in the treatment of [[pain]].<ref name="pmid25693108">{{cite journal | vauthors = Narver HL | title = Nalbuphine, a non-controlled opioid analgesic, and its potential use in research mice | journal = Lab Animal | volume = 44 | issue = 3 | pages = 106–110 | date = March 2015 | pmid = 25693108 | doi = 10.1038/laban.701 | s2cid = 25378355 }}</ref><ref name="pmid2986929">{{cite journal | vauthors = Schmidt WK, Tam SW, Shotzberger GS, Smith DH, Clark R, Vernier VG | title = Nalbuphine | journal = Drug and Alcohol Dependence | volume = 14 | issue = 3-43–4 | pages = 339–362 | date = February 1985 | pmid = 2986929 | doi = 10.1016/0376-8716(85)90066-3 }}</ref><ref name="SmithPappagallo2012">{{cite book| vauthors = Smith HS, Pappagallo M |title=Essential Pain Pharmacology: The Prescriber's Guide|url=https://books.google.com/books?id=ymry3quAw6IC&pg=PA343|date=6 September 2012|publisher=Cambridge University Press|isbn=978-0-521-75910-6|pages=343–}}</ref> It is given by [[injection (medicine)|injection]] into a [[vein]], [[muscle]], or [[fat]].<ref name="pmid25693108" /><ref name="SmithPappagallo2012" />

[[Side effect]]s of nalbuphine include [[sedation]], [[sweatiness]], [[wikt:clamminess|clamminess]], [[nausea]], [[vomiting]], [[dizziness]], [[vertigo]], [[dry mouth]], and [[headache]].<ref name="pmid2986929" /> Unlike other opioids, it has little to no capacity forto cause [[euphoria]] or [[respiratory depression]].<ref name="pmid25693108" /><ref name="pmid2986929" /> ItThere alsois hasalso little to no incidence of [[dysphoria]], [[dissociative|dissociation]], [[hallucination]]s, and related side effects at typical therapeutic doses.<ref name="pmid25693108" /><ref name="pmid2986929" /> Nalbuphine is a [[agonist-antagonist|mixed agonist/antagonist]] [[opioid modulator]].<ref name="pmid25693108" /><ref name="pmid2986929" /> Specifically, it acts as a moderate-[[efficacy]] [[partial agonist]] or [[receptor antagonist|antagonist]] of the [[μ-opioid receptor]] (MOR) and as a high-efficacy partial agonist of the [[κ-opioid receptor]] (KOR), whereas it has relatively low [[affinity (pharmacology)|affinity]] for the [[δ-opioid receptor]] (DOR) and [[sigma receptor]]s.<ref name="PengKnapp2007" /><ref name="pmid2986929" />

Nalbuphine is indicated for the relief of moderate to severe pain. It can also be used as a supplement to [[balanced anesthesia]], for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery. However, a [[doi:10.1002/14651858.CD009583.pub2|2014 Cochrane Systematic Review]] concluded that from the included studies, there was limited evidence to demonstrate that "0.1 to 0.3mg3{{nbs}}mg/kg nalbuphine compared to placebo might be an effective postoperative analgesic" for pain treatment in children.<ref name=":0">{{cite journal | vauthors = Schnabel A, Reichl SU, Zahn PK, Pogatzki-Zahn E | title = Nalbuphine for postoperative pain treatment in children | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD009583 | date = July 2014 | volume = 2016 | pmid = 25079857 | doi = 10.1002/14651858.CD009583.pub2 | doi-access = free | pmc = 10403789 }}</ref> Further research is therefore needed to compare nalbuphine with other postoperative opioids.<ref name=":0" />

Although nalbuphine possesses opioid antagonist activity, there is evidence that in nondependent patients it will not antagonize an opioid analgesic administered just before, concurrently, or just after an injection. Therefore, patients receiving an opioid analgesic, general anesthetics, phenothiazines, or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including [[alcohol (drug)|alcohol]]) concomitantly with Nalbuphine may exhibit an additive effect. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

Morphine induced pruritus syndrome may also be caused by release of histamine from [[mast cellscell]]s in the skin (Gunion et al. (2004). Paus et al. (2006) report that MORs and KORs are located in skin nerves and keratinocytes.

Levy et al. (1989) reviewed the literature on the relationship of opioid mediated histamine release from cutaneous mast cells to the etiology of hypotension, flushing and pruritus. The authors investigated the relative abilities of various opioids to induce histamine release mediated increased capillary permeability and tissue edema (“wheal"wheal response”response") and cutaneous vasodilatation and local redness (“flare"flare response”response") when subjects were intradermally injected with 0.02 ml equimolar concentrations of 5 x 10-4 M. Nalbuphine did not produce either a wheal or flare response.

Nalbuphine is available in two concentrations, 10&nbsp;mg and 20&nbsp;mg of nalbuphine hydrochloride per mL. Both strengths contain 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous, 0.1% sodium metabisulfite, and 0.2% of a 9:1 mixture of methylparaben and propylparaben as preservatives; pH is adjusted, if necessary, with [[hydrochloric acid]]. The 10&nbsp;mg/mL strength contains 0.1% sodium chloride. The drug is also available in a [[sulfite]] and paraben-free formulation in two concentrations, 10&nbsp;mg and 20&nbsp;mg of nalbuphine hydrochloride per mL. One mL of each strength contains 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous; pH is adjusted, if necessary, with hydrochloric acid. The 10&nbsp;mg/mL strength contains 0.2% sodium chloride.

An investigational extended-release oral formulation is under development by [Trevi Therapeutics.<ref>{{cite web |title=Haduvio™ |url=https://www.trevitherapeutics.com/haduvio/ |publisher=Trevi Therapeutics]. |access-date=3 September 2024 |language=en}}</ref>

Like pure MOR agonists, the mixed agonist/antagonist opioid class of drugs can cause side effects with initial administration of the drug which lessens over time (“"[[Drug tolerance|tolerance]]”"). This is particularly true for the side effects of nausea, sedation and cognitive symptoms (Jovey et al. 2003). These side effects can in many instances be ameliorated or avoided at the time of drug initiation by titrating the drug from a tolerable starting dose up to the desired therapeutic dose. An important difference between nalbuphine and the pure MOR agonist opioid analgesic drugs is the “ceiling"ceiling effect”effect" on respiration (but no ceiling on the analgesic effect). Respiratory depression is a potentially fatal side effect from the use of pure MOR agonists. Nalbuphine has limited ability to depress respiratory function (Gal et al. 1982).

Nalbuphine is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis, which is based on relative potency studies using intramuscular administration (Beaver et al. 1978). Oral administered nalbuphine is reported to be three times more potent than codeine (Okun et al. 1982). Clinical trials studied single dose experimental oral immediate release nalbuphine tablets for analgesic efficacy over a four- to six-hour time period following administration. Nalbuphine in the 15 to 60&nbsp;mg range had similar analgesic effects to immediate release codeine in the 30 to 60&nbsp;mg range (Kantor et al. 1984; Sunshine et al. 1983). Schmidt et al. (1985) reviewed the preclinical pharmacology of nalbuphine and reported comparative data relative to other types of opioid compounds. The authors point out that the nalbuphine [[Moiety (chemistry)|moiety]] is approximately ten times more pharmacologically potent than the mixed opioid agonist/antagonist [[butorphanol]] on an "antagonist index" scale which quantitates the drug's ability to act both as an analgesic (via opioid KOR agonism) as well as a MOR antagonist. The opioid antagonist activity of nalbuphine is one-fourth as potent as [[nalorphine]] and 10&nbsp;times that of [[pentazocine]].

[[Category:PhenolsHydroxyarenes]]