Chemistry:Butorphanol

From HandWiki

Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers.[1][2][3] Butorphanol is most closely structurally related to levorphanol.[citation needed] Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs, cats and horses due to low bioavailability in humans.

It was patented in 1971 and approved for medical use in 1979.[4]

Medical uses

The most common indication for butorphanol is management of migraine using the intranasal spray formulation. It may also be used parenterally for management of moderate-to-severe pain, as a supplement for balanced general anesthesia, and management of pain during labor. Butorphanol is also quite effective at reducing post-operative shivering (owing to its kappa agonist activity). Butorphanol is more effective in reducing pain in women than in men.[5]

Pharmacology

Butorphanol exhibits partial agonist and antagonist activity at the μ-opioid receptor, as well as partial agonist activity at the κ-opioid receptor (Ki = 2.5 nM; EC50 = 57 nM; Emax = 57%).[5][6] Stimulation of these receptors on central nervous system neurons causes an intracellular inhibition of adenylate cyclase, closing of influx membrane calcium channels, and opening of membrane potassium channels. This leads to hyperpolarization of the cell membrane potential and suppression of action potential transmission of ascending pain pathways. Because of its κ-agonist activity, at analgesic doses butorphanol increases pulmonary arterial pressure and cardiac work. Additionally, κ-agonism can cause dysphoria at therapeutic or supratherapeutic doses; this gives butorphanol a lower potential for abuse than other opioid drugs.[7]

Society and culture

Name

Within the INN, USAN, BAN, and AAN naming systems this drug is known as butorphanol, while within JAN it is named torbugesic.[1][2][3] As the tartrate salt, butorphanol is known as butorphanol tartrate (USAN, BAN).[1][2][3]

Butorphanol is listed under the Single Convention on Narcotic Drugs 1961 and in the United States is a Schedule IV controlled substance with a DEA ACSCN of 9720.[8] The free base conversion ratio of the hydrochloride is 0.69.[9] Butorphanol was originally a Schedule II controlled substance and was later decontrolled at one point.

Veterinary use

In veterinary anesthesia, butorphanol (trade name: Torbugesic) is widely used as a sedative and analgesic in dogs, cats and horses. For sedation, it may be combined with tranquilizers such as alpha-2 agonists (medetomidine), benzodiazepines, or acepromazine in dogs, cats and exotic animals. It is frequently combined with xylazine or detomidine in horses.[10] Butorphanol may be administered intravenously, intramuscularly, subcutaneously, or per os. Intramuscular and subcutaneous administration may cause pain. Oral tablets have poor bioavailability and are not suitable for analgesia. Instranasal usage has been reported in parrots and rabbits.[11] Butorphanol when administered at 0.4 mg/kg given IV/IM does not provide sufficient post-operative analgesia for laparotomy and shoulder arthrotomy in dogs and ovariohysterectomy in bitches.[11][12][13][14] When butorphanol is used as a sedative in dogs—either on its own or with dexmedetomidine—it provides fast sedation and is faster than sedation with methadone.[11][15][16] Butorphanol is also approved as an antitussive in the dog.[11]

Butorphanol has antiemetic properties, which counteracts the nausea-induced by dexmedetomidine.[17][11] Butorphanol's antiemetic properties are greater than that of buprenorphine.[11][18] Doses of 0.1–0.4 mg/kg IM in cats provides appropriate sedation but greater sedation may be achieved with full μ-opioid receptor agonists.[19] Butorphanol when administered alongside meloxicam, lidocaine, and dexmedetomidine provides appropriate analgesia for orchidectomy and reduces the mean alveolar concentration for isoflurane more than buprenorphine. Butorphanol can reduce the MAC 23–68%.[11][20][21]

As a mixed agonist-antagonist butorphanol can reverse some effects of full-opioid such as bradycardia and respiratory depression whilst maintaining analgesia.[11]

Although butorphanol is commonly used for pain relief in reptiles, no studies (as of 2014) have conclusively shown that it is an effective analgesic in reptiles.[22]

Use in horses

Butorphanol is a narcotic used for pain relief in horses.[23] It is administered either IM or IV, with its analgesic properties beginning to take effect about 15 minutes after injection and lasting 4 hours.[24][11] In healthy horses butorphanol increases locomotive activity, but the administration of a sedative e.g. xylazine or acepromazine prevents locomotion. In neonatal foals this effect is not observed and instead butorphanol produces sedation.[25] Pre-operative butorphanol administered intravenously at 0.02–0.1 mg/kg provides adequate post-operative analgesia for elective surgeries;[11][26][27] however, one study found that pre-operative butorphanol (0.01 mg/kg IV) combined with detomidine did not provide adequate post-operative analgesia.[28][11]

See also

References

  • Basic & Clinical Pharmacology (8th ed.). New York: McGraw-Hill. 2001. ISBN 978-0-8385-0598-4. 
  • Pharmacotherapy: A Pathophysiologic Approach (6th ed.). New York: McGraw-Hill. 2005. ISBN 0-07-141613-7. 
  • Equine Medications (Revised ed.). Lexington, Kentucky: Blood Horse Publications. 2007. 
  • The Merck Manual of Veterinary Medicine. 2004. 
  1. ↑ 1.0 1.1 1.2 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 200–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA200. 
  2. ↑ 2.0 2.1 2.2 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 154–. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA154. 
  3. ↑ 3.0 3.1 3.2 Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. 6 December 2012. pp. 58–. ISBN 978-94-011-4439-1. https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA58. 
  4. ↑ (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 529. ISBN 978-3-527-60749-5. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA529. 
  5. ↑ 5.0 5.1 "The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain". Pain 83 (2): 339–45. November 1999. doi:10.1016/S0304-3959(99)00119-0. PMID 10534607. 
  6. ↑ "Pharmacological profiles of opioid ligands at kappa opioid receptors". BMC Pharmacology 6 (1). January 2006. doi:10.1186/1471-2210-6-3. PMID 16433932. 
  7. ↑ "Critical Review of Butorphanol". 34th ECDD 2006/4.1. World Health Organization. https://www.who.int/medicines/areas/quality_safety/4.1ButhorphanolCritReview.pdf. 
  8. ↑ "Controlled Substances - by Controlled Substance Code Number". US Department of Justice / Drug Enforcement Administration. https://www.deadiversion.usdoj.gov/schedules/orangebook/d_cs_drugcode.pdf. 
  9. ↑ "Conversion Factors for Controlled Substances". Diversion Control Division. US Drug Enforcement Administration. http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html. 
  10. ↑ Compendium of Data sheets for Animal Medicines. 2005.. National Office of Animal Health. October 2004. ISBN 978-0-9548037-0-4. 
  11. ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 "Opioids". Veterinary Anesthesia and Analgesia, The 6th Edition of Lumb and Jones. Wiley Blackwell. 11 September 2024. pp. 382–383. ISBN 978-1-119-83027-6. 
  12. ↑ "Antioxidant and analgesic potential of butorphanol in dogs undergoing ovariohysterectomy". Theriogenology 190: 1–7. September 2022. doi:10.1016/j.theriogenology.2022.07.002. PMID 35849850. 
  13. ↑ "Evaluation of nalbuphine, butorphanol and morphine in dogs during ovariohysterectomy and on early postoperative pain". Veterinary Anaesthesia and Analgesia 47 (6): 803–809. November 2020. doi:10.1016/j.vaa.2020.07.035. PMID 32891492. 
  14. ↑ "A comparison of ketorolac with flunixin, butorphanol, and oxymorphone in controlling postoperative pain in dogs". The Canadian Veterinary Journal 37 (9): 557–567. September 1996. PMID 8877043. 
  15. ↑ "Comparison of sedation in dogs: methadone or butorphanol in combination with dexmedetomidine intravenously". Veterinary Anaesthesia and Analgesia 45 (5): 597–603. September 2018. doi:10.1016/j.vaa.2018.03.008. PMID 30077553. 
  16. ↑ "Effect of premedication with butorphanol or methadone on ease of endoscopic duodenal intubation in dogs". Veterinary Anaesthesia and Analgesia 44 (6): 1296–1302. November 2017. doi:10.1016/j.vaa.2017.05.004. PMID 29174961. 
  17. ↑ "The effect of butorphanol on the incidence of dexmedetomidine-induced emesis in cats". Veterinary Anaesthesia and Analgesia 42 (6): 608–613. November 2015. doi:10.1111/vaa.12260. PMID 25819160. 
  18. ↑ "Comparison of intramuscular butorphanol and buprenorphine combined with dexmedetomidine for sedation in cats". Journal of Feline Medicine and Surgery 20 (4): 325–331. April 2018. doi:10.1177/1098612X17709612. PMID 28548551. 
  19. ↑ "Sedation quality of alfaxalone associated with butorphanol, methadone or pethidine in cats injected into the supraspinatus or the quadriceps muscle". Journal of Feline Medicine and Surgery 24 (8): e269–e280. August 2022. doi:10.1177/1098612X221104747. PMID 35762271. 
  20. ↑ "Effect of intravenous butorphanol infusion on the minimum alveolar concentration of isoflurane in cats". Veterinary Anaesthesia and Analgesia 49 (2): 165–172. March 2022. doi:10.1016/j.vaa.2021.12.004. PMID 35033447. 
  21. ↑ "A randomized clinical trial comparing butorphanol and buprenorphine within a multimodal analgesic protocol in cats undergoing orchiectomy". Journal of Feline Medicine and Surgery 22 (8): 760–767. August 2020. doi:10.1177/1098612X19886132. PMID 31697181. 
  22. ↑ "Chapter 18: Analgesia". Current therapy in reptile medicine & surgery. Elsevier Health Sciences. 2014. pp. 217–229. ISBN 978-0-323-24293-6. 
  23. ↑ "Comparison of hydromorphone and butorphanol for management of pain in equine patients undergoing elective arthroscopy: a randomized clinical trial". Veterinary Anaesthesia and Analgesia 49 (5): 490–498. September 2022. doi:10.1016/j.vaa.2022.05.006. PMID 35752564. 
  24. ↑ "Analgesic effects of butorphanol in horses: dose-response studies". American Journal of Veterinary Research 45 (2): 211–216. February 1984. doi:10.2460/ajvr.1984.45.02.211. PMID 6711944. 
  25. ↑ "Pharmacokinetics of Butorphanol and Evaluation of Physiologic and Behavioral Effects after Intravenous and Intramuscular Administration to Neonatal Foals". Journal of Veterinary Internal Medicine 22 (6): 1417–1426. 2008. doi:10.1111/j.1939-1676.2008.0200.x. ISSN 0891-6640. PMID 18976284. https://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2008.0200.x. 
  26. ↑ "Comparison of hydromorphone and butorphanol for management of pain in equine patients undergoing elective arthroscopy: a randomized clinical trial". Veterinary Anaesthesia and Analgesia 49 (5): 490–498. 2022. doi:10.1016/j.vaa.2022.05.006. PMID 35752564. https://linkinghub.elsevier.com/retrieve/pii/S1467298722000939. 
  27. ↑ "A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery". Equine Veterinary Journal 48 (4): 442–450. 2016. doi:10.1111/evj.12442. ISSN 0425-1644. PMID 25772950. 
  28. ↑ "Analgesic effect of butorphanol in ponies following castration". Equine Veterinary Journal (Wiley) 41 (6): 552–556. 2009. doi:10.2746/042516409x391024. ISSN 0425-1644. PMID 19803050. 



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