Dr. Bob Stein

We hope to periodically present new and/or timely material reviews on this page. Our current topic is Nalbuphine (Nubain). Nalbuphine is a mixed agonist/antagonist with qualities similar to butorphanol. It is primarily a kappa agonist with antagonistic properties at the mu opioid receptor. As with butorphanol, nalbuphine possesses mild analgesia properties of short duration. Nalbuphine can be used to antagonize unwanted mu agonist effects without totally eliminating analgesia making it attractive when the patient is exhibiting excessive sedation, respiratory depression, or dysphoria. Nalbuphine is remarkably free of adverse cardiovascular or respiratory effects. At doses far above any clinically relevant dose, excitation and dysphoria are possible adverse consequences.


  • Kappa agonist/mu antagonist
  • Currently a nonscheduled drug (no required paperwork of any kind)
  • Currently costs much less than butorphanol
  • Free of significant adverse effects - no expected negative CV, respiratory, or GI effects
  • Analgesia best suited to mild pain only
  • Short duration of analgesic and sedative effect
  • Mild sedation alone - marked synergism with the alpha-2 agonist medetomidine
  • Mild MAC sparing effect as sole agent
  • Appears well suited to early shock management - initial analgesia, improved CV stability
  • Effective routes of delivery include the IV and IM routes (not effective PO)

Details and references


MU OPIOID AGONIST ANTAGONISM nalbuphine is an excellent option for titration/reversal of unwanted mu agonist effects such as excess sedation or prolonged anesthetic recovery and respiratory depression without the loss of all analgesia,[1][2].


FREEDOM OF ADVERSE EFFECTS nalbuphine is generally free of any adverse cardiovascular, respiratory, or gastrointestinal adverse effects[3],[4][3],[4],[5],[6],[7],[8].


ANALGESIC PROPERTIES nalbuphine provides mild analgesia or short duration[4],[6],[9].


SEDATION nalbuphine provides minimal sedation as a sole agent in healthy patients. Sedation may be more consistent in depressed patients. When combined with the alpha-2 agonist, medetomidine, significant short duration sedation and enhanced analgesia are predictable even in young, healthy patients[1],[6].


MILD MAC SPARING EFFECT nalbuphine has been shown to reduce enflurane MAC at doses as low as 0.5 mg/kg[10].


BENEFICIAL EFFECTS DURING SHOCK nalbuphine has been shown to improve patient survivability at doses from 1 to 5 mg/kg[11],[12].


INEFFECTIVE WHEN DELIVERED ORALLY oral bioavailability is approximately 5%[13].

[1] Mills CA, Flacke JW, Flacke WE, Bloor BC, Liu MD: Narcotic reversal in hypercapnic dogs: comparison of naloxone and nalbuphine. Can J Anaesth Mar;37(2):238-44, 1990

[2] Jacobson JD, McGrath CJ, Smith EP: Cardiorespiratory effects of four opioid-tranquilizer combinations in dogs. Vet Surg Sep-Oct;23(5):434, 1994

[3] Lester PA, Gaynor JS, Hellyer PW, Mama K, Wagner AE: The sedative and behavioral effects of nalbuphine in dogs. Contemp Top Lab Anim Sci. Jul;42(4):27-31, 2003

[4] Muldoon SM, Donlon MA, Todd R, Helgeson EA, Freas W: Plasma histamine and hemodynamic responses following administration of nalbuphine and morphine. Agents Actions Oct;15(3-4):229-34, 1984

[5] Schmidt WK, Tam SW, Shotzberger GS, Smith DH Jr, Clark R, Vernier VG: Nalbuphine. Drug Alcohol Depend Feb;14(3-4):339-62, 1985

[6] Sawyer DC, Rech RH: Analgesia and behavioral effects of butorphanol, nalbuphine, and pentazocine in the cat. J Am An Hosp Assoc 23:438, 1987

[7] Sawyer dc, Anderson DL, Scott JB: Cardiovascular effects and clinical use of nalbuphine in the dog. Proceedings of the Assoc of Vet Anesth of Great Britain and Ireland 10:215, 1982

[8] Pascoe PJ: Opioid analgesics. Vet Clin North Am Small Anim Pract Jul;30(4):757-72, 2000

[9] Flecknell PA, Kirk AJ, Liles JH, Hayes PH, Dark JH: Post-operative analgesia following thoracotomy in the dog: an evaluation of the effects of bupivacaine intercostal nerve block and nalbuphine on respiratory function. Lab Anim Oct;25(4):319-24, 1991

[10] Murphy MR, Hug CC Jr: The enflurane sparing effect of morphine, butorphanol, and nalbuphine. Anesthesiology Dec;57(6):489-92, 1982

[11] McKenzie JE, Anselmo DM, Muldoon SM: Nalbuphine's reversal of hypovolemic shock in the anesthetized rat. Circ Shock 17(1):21-33, 1985

[12] Hunt LB, Gurll NJ, Reynolds DG: Dose-dependent effects of nalbuphine in canine hemorrhagic shock. Circ Shock 13(4):307-18, 1984

[13] Hussain MA, Aungst BJ, Koval CA, Shefter E: Improved buccal delivery of opioid analgesics and antagonists with bitterless prodrugs. Pharm Res Sep;5(9):615-8, 1988


VASG videos demonstrating combined nalbuphine/medetomidine effects on dogs and cats 




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Questions or problems regarding this web site should be directed to DRSTEIN@VASG.ORG .
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Last modified: Friday February 06, 2009.