Parenteral potent opioid availability is becoming an issue in acute pain management. Two opioids, nalbuphine and buprenorphine, are available which can be substituted for hydromorphone, fentanyl, and morphine. There are advantages and disadvantages in using these 2 opioids which are discussed, and potential dosing strategies are outlined.
De SouzaEBSchmidtWKKuharMJ. Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988;244(1):391–402.
4.
SchmidtWKMarynowskiMESmithC. Nalbuphine, pentazocine, and butorphanol interactions with tripelennamine in mice. NIDA Res Monogr. 1986;67:145–146.
5.
PickCGPaulDPasternakGW. Nalbuphine, a mixed kappa 1 and kappa 3 analgesic in mice. J Pharmacol Exp Ther. 1992;262(3):1044–1050.
6.
JannuzziRG. Nalbuphine for treatment of opioid-induced pruritus: a systematic review of literature. Clin J Pain. 2016;32(1):87–93.
7.
RaehalKMLoweryJJBhamidipatiCM. In vivo characterization of 6beta-naltrexol, an opioid ligand with less inverse agonist activity compared with naltrexone and naloxone in opioid-dependent mice. J Pharmacol Exp Ther. 2005;313(3):1150–1162.
8.
YehYCLinTFChangHC. Combination of low-dose nalbuphine and morphine in patient-controlled analgesia decreases incidence of opioid-related side effects. J Formos Med Assoc. 2009;108(7):548–553.
9.
YehYCLinTFLinFSWangYPLinCJSunWZ. Combination of opioid agonist and agonist-antagonist: patient-controlled analgesia requirement and adverse events among different-ratio morphine and nalbuphine admixtures for postoperative pain. Br J Anaesth. 2008;101(4):542–548.
10.
LataschLTeichmullerTDudziakRProbstS. Antagonisation of fentanyl-induced respiratory depression by nalbuphine. Acta Anaesthesiol Belg. 1989;40(1):35–40.
11.
LataschLProbstSDudziakR. Reversal by nalbuphine of respiratory depression caused by fentanyl. Anesth Analg. 1984;63(9):814–816.
12.
FreyeEAzevedoLHartungE. Reversal of fentanyl related respiratory depression with nalbuphine. Effects on the CO2-response curve in man. Acta Anaesthesiol Belg. 1985;36(4):365–374.
13.
ElliottHWNavarroGNomofN. A double blind controlled study of the pharmacologic effects of nalbuphine (EN-2234A). J Med. 1970;1(2):74–89.
14.
TeterKAViellionGKeatingEM. Patient controlled analgesia and GI dysfunction. Orthop Nurs. 1990;9(4):51–56.
15.
ShookJEPeltonJTHrubyVJBurksTF. Peptide opioid antagonist separates peripheral and central opioid antitransit effects. J Pharmacol Exp Ther. 1987;243(2):492–500.
16.
ParkerRKHoltmannBWhitePF. Patient-controlled epidural analgesia: interactions between nalbuphine and hydromorphone. Anesth Analg. 1997;84(4):757–763.
17.
MalinovskyJMLepageJYKaramGPinaudM. Nalbuphine reverses urinary effects of epidural morphine: a case report. J Clin Anesth. 2002;14(7):535–538.
18.
LakeCLDuckworthENDiFazioCAMagruderMR. Cardiorespiratory effects of nalbuphine and morphine premedication in adult cardiac surgical patients. Acta Anaesthesiol Scand. 1984;28(3):305–309.
19.
LakeCLDuckworthENDiFazioCADurbinCGMagruderMR. Cardiovascular effects of nalbuphine in patients with coronary or valvular heart disease. Anesthesiology. 1982;57(6):498–503.
20.
RothAKerenGGluckABraunSLaniadoS. Comparison of nalbuphine hydrochloride versus morphine sulfate for acute myocardial infarction with elevated pulmonary artery wedge pressure. Am J Cardiol. 1988;62(9):551–555.
21.
DesevaBMuikovaNVitanovaM, Iosifova S. The effect of nalbuphine hydrochloride (Nubain) on respiration in surgical patients. Khirurgiia (Sofiia). 1993;46(2):18–21.
22.
RawalNWennhagerM. Influence of perioperative nalbuphine and fentanyl on postoperative respiration and analgesia. Acta Anaesthesiol Scand. 1990;34(3):197–202.
23.
SeitzWLubbeNKirchnerE. Effect of nalbuphine on respiration. Anaesthesist. 1986;35(2):108–110.
24.
MajumdarSGrinnellSLe RouzicV. Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc Natl Acad Sci USA. 2011;108(49):19778–19783.
25.
XuJXuMRossiGCPasternakGWPanYX. Identification and characterization of seven new exon 11-associated splice variants of the rat mu opioid receptor gene, OPRM1. Mol Pain. 2011;7:9.
26.
GrinnellSGMajumdarSNarayanA. Pharmacologic characterization in the rat of a potent analgesic lacking respiratory depression, IBNtxA. J Pharmacol Exp Ther. 2014;350(3):710–718.
27.
GrinnellSGAnsonoffMMarroneGF. Mediation of buprenorphine analgesia by a combination of traditional and truncated mu opioid receptor splice variants. Synapse. 2016;70(10):395–407.
28.
LoMWScharyWLWhitneyCCJr. The disposition and bioavailability of intravenous and oral nalbuphine in healthy volunteers. J Clin Pharmacol. 1987;27(11):866–873.
29.
LoMWLeeFHScharyWLWhitneyCCJr. The pharmacokinetics of intravenous, intramuscular, and subcutaneous nalbuphine in healthy subjects. Eur J Clin Pharmacol. 1987;33(3):297–301.
30.
LoMWJuergensGP, Whitney CC Jr. Determination of nalbuphine in human plasma by automated high-performance liquid chromatography with electrochemical detection. Res Commun Chem Pathol Pharmacol. 1984;43(1):159–168.
31.
WangHJHsiongCHHoST. Commonly used excipients modulate UDP-glucuronosyltransferase 2b7 activity to improve nalbuphine oral bioavailability in humans. Pharm Res. 2014;31(7):1676–1688.
32.
HawiAAlcornHJrBergJHinesCHaitHSciasciaT. Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus. BMC Nephrol. 2015;16:47.
33.
BeaverWTFeiseGA. A comparison of the analgesic effect of intramuscular nalbuphine and morphine in patients with postoperative pain. J Pharmacol Exp Ther. 1978;204(2):487–496.
34.
ZacnyJPConleyKMarksS. Comparing the subjective, psychomotor and physiological effects of intravenous nalbuphine and morphine in healthy volunteers. J Pharmacol Exp Ther. 1997;280(3):1159–1169.
35.
ZengZLuJShuC. A comparision of nalbuphine with morphine for analgesic effects and safety: meta-analysis of randomized controlled trials. Sci Rep. 2015;5:10927.
36.
KrennHOczenskiWJellinekHKrumpl-StroherMSchweitzerEFitzgeraldRD. Nalbuphine by PCA-pump for analgesia following hysterectomy: bolus application versus continuous infusion with bolus application. Eur J Pain. 2001;5(2):219–226.
37.
WoollardMWhitfieldRSmithK. Less IS less: a randomised controlled trial comparing cautious and rapid nalbuphine dosing regimens. Emerg Med J. 2004;21(3):362–364.
38.
JangSKimHKimD. Attenuation of morphine tolerance and withdrawal syndrome by coadministration of nalbuphine. Arch Pharm Res. 2006;29(8):677–684.
39.
LaubyVMallaretMRiviereIBartheICoquilhatP. Precipitation of opioid withdrawal syndrome with nalbuphine in a morphine dependent cancer patient. Therapie. 1994;49(2):143–144.
40.
JasinskiDRManskyPA. Evaluation of nalbuphine for abuse potential. Clin Pharmacol Ther. 1972;13(1):78–90.
41.
WinesJDJrGruberAJPopeHGJrLukasSE. Nalbuphine hydrochloride dependence in anabolic steroid users. Am J Addict. 1999;8(2):161–164.
42.
AitkenheadARLinESAcholaKJ. The pharmacokinetics of oral and intravenous nalbuphine in healthy volunteers. Br J Clin Pharmacol. 1988;25(2):264–268.
43.
BeaverWTFeiseGARobbD. Analgesic effect of intramuscular and oral nalbuphine in postoperative pain. Clin Pharmacol Ther. 1981;29(2):174–180.
44.
TraynorJRGuoLCoopALewisJWWoodsJH. Ring-constrained orvinols as analogs of buprenorphine: differences in opioid activity related to configuration of C(20) hydroxyl group. J Pharmacol Exp Ther. 1999;291(3):1093–1099.
45.
ZakiPAKeithDEJrBrineGACarrollFIEvansCJ. Ligand-induced changes in surface mu-opioid receptor number: relationship to G protein activation?J Pharmacol Exp Ther. 2000;292(3):1127–1134.
46.
McPhersonJRiveroGBaptistM. mu-opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization. Mol Pharmacol. 2010;78(4):756–766.
47.
YuYZhangLYinXSunHUhlGRWangJB. Mu opioid receptor phosphorylation, desensitization, and ligand efficacy. J Biol Chem. 1997;272(46):28869–28874.
48.
SittlRNuijtenMNautrupBP. Patterns of dosage changes with transdermal buprenorphine and transdermal fentanyl for the treatment of noncancer and cancer pain: a retrospective data analysis in Germany. Clin Ther. 2006;28(8):1144–1154.
49.
CowanA. Buprenorphine: the basic pharmacology revisited. J Addict Med. 2007;1(2):68–72.
50.
KressHG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. Eur J Pain. 2009;13(3):219–230.
51.
KogelBChristophTStrassburgerWFriderichsE. Interaction of mu-opioid receptor agonists and antagonists with the analgesic effect of buprenorphine in mice. Eur J Pain. 2005;9(5):599–611.
52.
GalliganJJAkbaraliHI. Molecular physiology of enteric opioid receptors. Am J Gastroenterol Suppl. 2014;2(1):17–21.
53.
MercadanteSCasuccioATirelliWGiarratanoA. Equipotent doses to switch from high doses of opioids to transdermal buprenorphine. Support Care Cancer. 2009;17(6):715–718.
AndresenTStaahlCOkscheAMansikkaHArendt-NielsenLDrewesAM. Effect of transdermal opioids in experimentally induced superficial, deep and hyperalgesic pain. Br J Pharmacol. 2011;164(3):934–945.
56.
WalaEPHoltmanJR, Jr. Buprenorphine-induced hyperalgesia in the rat. Eur J Pharmacol. 2011;651(1-3):89–95.
57.
KoppertWIhmsenHKorberN. Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model. Pain. 2005;118(1-2):15–22.
DahanAYassenA, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth. 2006;96(5):627–632.
60.
HeitHAGourlayDL. Buprenorphine: new tricks with an old molecule for pain management. Clin J Pain. 2008;24(2):93–97.
61.
SloanP. Buprenorphine for chronic pain management. J Support Oncol. 2012;10(6):220–1.
62.
MacintyrePEHuxtableCA. Buprenorphine for the management of acute pain. Anaesth Intensive Care. 2017;45(2):143–146.
63.
HuxtableCAMacintyrePE. An alternative way of managing acute pain in patients who are in buprenorphine opioid substitution therapy programs. Eur J Anaesthesiol. 2013;30(11):717–718.
64.
MacintyrePERussellRAUsherKAGaughwinMHuxtableCA. Pain relief and opioid requirements in the first 24 hours after surgery in patients taking buprenorphine and methadone opioid substitution therapy. Anaesth Intensive Care. 2013;41(2):222–230.
65.
AndersonTAQuayeANAWardENWilensTEHilliardPEBrummettCM. To stop or not, that is the question: acute pain management for the patient on chronic buprenorphine. Anesthesiology. 2017;126(6):1180–1186.
66.
JasinskiDRPevnickJSGriffithJD. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen Psychiatry. 1978;35(4):501–516.
67.
TraynorJRNahorskiSR. Modulation by mu-opioid agonists of guanosine-5′-O-(3-[35S]thio)triphosphate binding to membranes from human neuroblastoma SH-SY5Y cells. Mol Pharmacol. 1995;47(4):848–854.
68.
BrownSMHoltzmanMKimTKharaschED. Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active. Anesthesiology. 2011;115(6):1251–1260.
69.
MercerSLCoopA. Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance. Curr Top Med Chem. 2011;11(9):1157–1164.
70.
HorvatCMAuAKConleyYPKochanekPMLiLPoloyacSM. ABCB1 genotype is associated with fentanyl requirements in critically ill children. Pediatr Res. 2017;82(1):29–35.
71.
AlhaddadHCisterninoSDeclevesXTournierNSchlatterJ, Chiadmi F, et al. Respiratory toxicity of buprenorphine results from the blockage of P-glycoprotein-mediated efflux of norbuprenorphine at the blood-brain barrier in mice. Crit Care Med. 2012;40(12):3215–3223.
72.
BrownSMCampbellSDCraffordAReginaKJHoltzmanMJKharaschED. P-glycoprotein is a major determinant of norbuprenorphine brain exposure and antinociception. J Pharmacol Exp Ther. 2012;343(1):53–61.
73.
PausawasdiSKanjanapitakAKanjanapanjapolS. The effect of buprenorphine and morphine on intraluminal pressure of the common bile duct. J Med Assoc Thai. 1984;67(6):329–333.
74.
BliesenerNAlbrechtSSchwagerAWeckbeckerKLichtermannDKlingmullerD. Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. J Clin Endocrinol Metab. 2005;90(1):203–206.
75.
FranchiSPaneraiAESacerdoteP. Buprenorphine ameliorates the effect of surgery on hypothalamus-pituitary-adrenal axis, natural killer cell activity and metastatic colonization in rats in comparison with morphine or fentanyl treatment. Brain Behav Immun. 2007;21(6):767–774.
76.
MartucciCPaneraiAESacerdoteP. Chronic fentanyl or buprenorphine infusion in the mouse: similar analgesic profile but different effects on immune responses. Pain. 2004;110(1-2):385–392.
77.
PergolizziJBogerRHBuddK. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract. 2008;8(4):287–313.
78.
CuschieriRJMorranCGMcArdleCS. Comparison of morphine and sublingual buprenorphine following abdominal surgery. Br J Anaesth. 1984;56(8):855–859.
79.
SittlRLikarRNautrupBP. Equipotent doses of transdermal fentanyl and transdermal buprenorphine in patients with cancer and noncancer pain: results of a retrospective cohort study. Clin Ther. 2005;27(2):225–237.
80.
MercadanteSPorzioGFerreraP. Low doses of transdermal buprenorphine in opioid-naive patients with cancer pain: a 4-week, nonrandomized, open-label, uncontrolled observational study. Clin Ther. 2009;31(10):2134–2138.
81.
WebsterLGruenerDKirbyTXiangQTzanisEFinnA. Evaluation of the tolerability of switching patients on chronic full mu-opioid agonist therapy to buccal buprenorphine. Pain Med. 2016;17(5):899–907.
82.
DaitchDDaitchJNovinsonDFreyMMitnickC, Pergolizzi J Jr. Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Pain Med. 2014;15(12):2087–2094.
83.
DaitchJFreyMESilverDMitnickCDaitchDPergolizziJJr. Conversion of chronic pain patients from full-opioid agonists to sublingual buprenorphine. Pain Physician. 2012;15(3 Suppl): ES59–66.
84.
KornfeldHReetzH. Transdermal buprenorphine, opioid rotation to sublingual buprenorphine, and the avoidance of precipitated withdrawal: a review of the literature and demonstration in three chronic pain patients treated with butrans. Am J Ther. 2015;22(3):199–205.
85.
FreyeEAnderson-HillemacherARitzdorfILevyJV. Opioid rotation from high-dose morphine to transdermal buprenorphine (Transtec) in chronic pain patients. Pain Pract. 2007;7(2):123–129.
86.
YeoAKChanCYChiaKH. Complications relating to intravenous buprenorphine abuse: a single institution case series. Ann Acad Med Singapore. 2006;35(7):487–491.
