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Paracetamol

Grade

Non-Surgical Analgesia

Therapeutics

Under Development

  • In Progress: Awaiting Data


Evidence

  1. Arenillas, M., Caro-Vadillo, A., Gómez de Segura, I.A., 2019. Anesthetic management of a dog with severe subaortic stenosis and mitral valve disease complicated with atrial fibrillation undergoing ovariohysterectomy. Open Vet J 9, 157–163. https://doi.org/10.4314/ovj.v9i2.11

  2. Bates, N., Rawson-Harris, P., Edwards, N., 2015. Common questions in veterinary toxicology. J Small Anim Pract 56, 298–306. https://doi.org/10.1111/jsap.12343

  3. Battersby, I.A., Murphy, K.F., Tasker, S., Papasouliotis, K., 2006. Retrospective study of fever in dogs: laboratory testing, diagnoses and influence of prior treatment. J Small Anim Pract 47, 370–376. https://doi.org/10.1111/j.1748-5827.2006.00042.x

  4. Benitez, M.E., Roush, J.K., McMurphy, R., KuKanich, B., Legallet, C., 2015. Clinical efficacy of hydrocodone-acetaminophen and tramadol for control of postoperative pain in dogs following tibial plateau leveling osteotomy. Am J Vet Res 76, 755–762. https://doi.org/10.2460/ajvr.76.9.755

  5. Botting, R., 2003. COX-1 and COX-3 inhibitors. Thromb. Res. 110, 269–272. https://doi.org/10.1016/s0049-3848(03)00411-0

  6. Budsberg, S.C., Kleine, S.A., Norton, M.M., Sandberg, G.S., Papich, M.G., 2020. Comparison of the effects on lameness of orally administered acetaminophen-codeine and carprofen in dogs with experimentally induced synovitis. Am J Vet Res 81, 627–634. https://doi.org/10.2460/ajvr.81.8.627

  7. Chervier, C., Chabanne, L., Godde, M., Rodriguez-Piñeiro, M.I., Deputte, B.L., Cadoré, J.-L., 2012. Causes, diagnostic signs, and the utility of investigations of fever in dogs: 50 cases. Can Vet J 53, 525–530.

  8. Colletti, A.E., Vogl, H.W., Rahe, T., Zambraski, E.J., 1999. Effects of acetaminophen and ibuprofen on renal function in anesthetized normal and sodium-depleted dogs. J Appl Physiol (1985) 86, 592–597. https://doi.org/10.1152/jappl.1999.86.2.592

  9. Engelhardt, G., Homma, D., Schlegel, K., Utzmann, R., Schnitzler, C., 1995. Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance. Inflamm Res 44, 423–433. https://doi.org/10.1007/BF01757699

  10. Fitzgerald, K.T., Bronstein, A.C., Flood, A.A., 2006. “Over-The-Counter” Drug Toxicities in Companion Animals. Clinical Techniques in Small Animal Practice, Practical Toxicology 21, 215–226. https://doi.org/10.1053/j.ctsap.2006.10.006

  11. Fletcher, J.R., 1982. The role of prostaglandins in sepsis. Scand J Infect Dis Suppl 31, 55–60.

  12. Francavilla, A., Azzarone, A., Carrieri, G., Cillo, U., Van Thiel, D., Subbottin, V., Starzl, T.E., 1993. Administration of hepatic stimulatory substance alone or with other liver growth factors does not ameliorate acetaminophen-induced liver failure. Hepatology 17, 429–433.

  13. Gates, M.C., Littlewood, K.E., Kongara, K., Odom, T.F., Sawicki, R.K., 2020. Cross-sectional survey of anaesthesia and analgesia protocols used to perform routine canine and feline ovariohysterectomies. Veterinary Anaesthesia and Analgesia 47, 38–46. https://doi.org/10.1016/j.vaa.2019.06.008

  14. Gazzard, B.G., Hughes, R.D., Mellon, P.J., Portmann, B., Williams, R., 1975. A dog model of fulminant hepatic failure produced by paracetamol administration. Br J Exp Pathol 56, 408–411.

  15. González-Blanco, P., Canfrán, S., Mota, R., Gómez de Segura, I.A., Aguado, D., 2020. Effects of a single paracetamol injection on the sevoflurane minimum alveolar concentration in dogs. Can J Vet Res 84, 37–43.

  16. Green, C.E., Dabbs, J.E., Tyson, C.A., 1984. Metabolism and cytotoxicity of acetaminophen in hepatocytes isolated from resistant and susceptible species. Toxicol Appl Pharmacol 76, 139–149. https://doi.org/10.1016/0041-008x(84)90037-1

  17. Harvey, J.W., French, T.W., Senior, D.F., 1986. Hematologic abnormalities associated with chronic acetaminophen administration in a dog. J Am Vet Med Assoc 189, 1334–1335.

  18. Hernández-Avalos, I., Valverde, A., Antonio Ibancovichi-Camarillo, J., Sánchez-Aparicio, P., Recillas-Morales, S., Rodríguez-Velázquez, D., Osorio-Avalos, J., Armando Magdaleno-Torres, L., Chavez-Monteagudo, J., Manuel Acevedo-Arcique, C., 2021a. Clinical Use of The Parasympathetic Tone Activity Index As a Measurement of Postoperative Analgaesia in Dogs Undergoing Ovariohysterectomy. J Vet Res 65, 117–123. https://doi.org/10.2478/jvetres-2021-0004

  19. Hernández-Avalos, I., Valverde, A., Antonio Ibancovichi-Camarillo, J., Sánchez-Aparicio, P., Recillas-Morales, S., Rodríguez-Velázquez, D., Osorio-Avalos, J., Armando Magdaleno-Torres, L., Chavez-Monteagudo, J., Manuel Acevedo-Arcique, C., 2021b. Clinical Use of The Parasympathetic Tone Activity Index As a Measurement of Postoperative Analgaesia in Dogs Undergoing Ovariohysterectomy. J Vet Res 65, 117–123. https://doi.org/10.2478/jvetres-2021-0004

  20. Hernández-Avalos, I., Valverde, A., Ibancovichi-Camarillo, J.A., Sánchez-Aparicio, P., Recillas-Morales, S., Osorio-Avalos, J., Rodríguez-Velázquez, D., Miranda-Cortés, A.E., 2020. Clinical evaluation of postoperative analgesia, cardiorespiratory parameters and changes in liver and renal function tests of paracetamol compared to meloxicam and carprofen in dogs undergoing ovariohysterectomy. PLoS ONE 15, e0223697. https://doi.org/10.1371/journal.pone.0223697

  21. Hjelle, J.J., Grauer, G.F., 1986. Acetaminophen-induced toxicosis in dogs and cats. J Am Vet Med Assoc 188, 742–746.

  22. Hornfeldt, C.S., 1992. Distinction made between toxicoses caused by acetaminophen and nonsteroidal anti-inflammatory drugs. J Am Vet Med Assoc 201, 1318–1319.

  23. Houston, D.M., Myers, S.L., 1993. A review of Heinz-body anemia in the dog induced by toxins. Vet Hum Toxicol 35, 158–161.

  24. Johnston, S.A., Fox, S.M., 1997. Mechanisms of action of anti-inflammatory medications used for the treatment of osteoarthritis. J Am Vet Med Assoc 210, 1486–1492.

  25. Jones, R.D., Baynes, R.E., Nimitz, C.T., 1992. Nonsteroidal anti-inflammatory drug toxicosis in dogs and cats: 240 cases (1989-1990). J Am Vet Med Assoc 201, 475–477.

  26. Kalantzi, L., Polentarutti, B., Albery, T., Laitmer, D., Abrahamsson, B., Dressman, J., Reppas, C., 2005. The delayed dissolution of paracetamol products in the canine fed stomach can be predicted in vitro but it does not affect the onset of plasma levels. Int J Pharm 296, 87–93. https://doi.org/10.1016/j.ijpharm.2005.02.028

  27. Koyanagi, T., Yamaura, Y., Yano, K., Kim, S., Yamazaki, H., 2014. Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs. Xenobiotica 44, 893–901. https://doi.org/10.3109/00498254.2014.903532

  28. KuKanich, B., 2016. Pharmacokinetics and pharmacodynamics of oral acetaminophen in combination with codeine in healthy Greyhound dogs. J. Vet. Pharmacol. Ther. 39, 514–517. https://doi.org/10.1111/jvp.12299

  29. KuKanich, B., 2010. Pharmacokinetics of acetaminophen, codeine, and the codeine metabolites morphine and codeine-6-glucuronide in healthy Greyhound dogs. J Vet Pharmacol Ther 33, 15–21. https://doi.org/10.1111/j.1365-2885.2009.01098.x

  30. MacNaughton, S.M., 2003. Acetaminophen toxicosis in a Dalmatian. Can Vet J 44, 142–144.

  31. Mariani, C.L., Fulton, R.B., 2001. Atypical Reaction to Acetaminophen Intoxication in a Dog. Journal of Veterinary Emergency and Critical Care 11, 123–126. https://doi.org/10.1111/j.1476-4431.2001.tb00078.x

  32. Mbugua, S., Skoglund, L., Løkken, P., 1989. Effects of phenylbutazone and indomethacin on the post-operative course following experimental orthopaedic surgery in dogs. Acta veterinaria Scandinavica 30. https://doi.org/10.1186/BF03548065

  33. Mburu, D.N., 1991. Evaluation of the anti-inflammatory effects of a low dose of acetaminophen following surgery in dogs. J Vet Pharmacol Ther 14, 109–111. https://doi.org/10.1111/j.1365-2885.1991.tb00811.x

  34. Mburu, D.N., Mbugua, S.W., Skoglund, L.A., Lökken, P., 1988. Effects of paracetamol and acetylsalicylic acid on the post-operative course after experimental orthopaedic surgery in dogs. J Vet Pharmacol Ther 11, 163–170. https://doi.org/10.1111/j.1365-2885.1988.tb00137.x

  35. McConkey, S.E., Grant, D.M., Cribb, A.E., 2009. The role of para-aminophenol in acetaminophen-induced methemoglobinemia in dogs and cats. J Vet Pharmacol Ther 32, 585–595. https://doi.org/10.1111/j.1365-2885.2009.01080.x

  36. Merrill, G.F., Merrill, J.H., Golfetti, R., Jaques, K.M., Hadzimichalis, N.S., Baliga, S.S., Rork, T.H., 2007. Antiarrhythmic properties of acetaminophen in the dog. Exp Biol Med (Maywood) 232, 1245–1252. https://doi.org/10.3181/0701-RM-19

  37. N, P., Ss, A., Pv, M., 2019. Comprehensive biology of antipyretic pathways. Cytokine 116, 120–127. https://doi.org/10.1016/j.cyto.2019.01.008

  38. Neirinckx, E., Vervaet, C., De Boever, S., Remon, J.P., Gommeren, K., Daminet, S., De Backer, P., Croubels, S., 2010. Species comparison of oral bioavailability, first-pass metabolism and pharmacokinetics of acetaminophen. Res Vet Sci 89, 113–119. https://doi.org/10.1016/j.rvsc.2010.02.002

  39. Nelson, K., 2019. Paracetamol toxicity in dogs. Veterinary Record 184, 594–594. https://doi.org/10.1136/vr.l2060

  40. Nielsen, L., Shaw, M., Morris, J., 2007. What is your diagnosis? Paracetamol poisoning. J Small Anim Pract 48, 121–124. https://doi.org/10.1111/j.1748-5827.2006.00145.x

  41. Ortega, L., Landa Garcia, J.I., Torres Garcia, A., Silecchia, G., Arenas, J., Suarez, A., Moreno Azcoitia, M., Sanz Esponera, J., Moreno Gonzalez, E., Balibrea Cantero, J.L., 1985. Acetaminophen-induced fulminant hepatic failure in dogs. Hepatology 5, 673–676. https://doi.org/10.1002/hep.1840050425

  42. Pacheco, M., Knowles, T.G., Hunt, J., Slingsby, L.S., Taylor, P.M., Murrell, J.C., 2020. Comparing paracetamol/codeine and meloxicam for postoperative analgesia in dogs: a non-inferiority trial. Vet Rec 187, e61. https://doi.org/10.1136/vr.105487

  43. Panella, C., Makowka, L., Barone, M., Polimeno, L., Rizzi, S., Demetris, J., Bell, S., Guglielmi, F.W., Prelich, J.G., Van Thiel, D.H., 1990. Effect of ranitidine on acetaminophen-induced hepatotoxicity in dogs. Dig Dis Sci 35, 385–391. https://doi.org/10.1007/BF01537419

  44. Piperno, E., Mosher, A.H., Berssenbruegge, D.A., Winkler, J.D., Smith, R.B., 1978. Pathophysiology of acetaminophen overdosage toxicity: implications for management. Pediatrics 62, 880–889.

  45. Rother, K.I., Schwenk, W.F., 1995. Hepatic glycogen accurately reflected by acetaminophen glucuronide in dogs refed after fasting. Am J Physiol 269, E766-773. https://doi.org/10.1152/ajpendo.1995.269.4.E766

  46. Rudolph, A.M., 1981. Effects of aspirin and acetaminophen in pregnancy and in the newborn. Arch. Intern. Med. 141, 358–363. https://doi.org/10.1001/archinte.141.3.358

  47. Sartini, I., Łebkowska-Wieruszewska, B., Lisowski, A., Poapolathep, A., Cuniberti, B., Giorgi, M., 2021. Pharmacokinetics of acetaminophen after intravenous and oral administration in fasted and fed Labrador Retriever dogs. J Vet Pharmacol Ther 44, 28–35. https://doi.org/10.1111/jvp.12893

  48. Savides, M.C., Oehme, F.W., Nash, S.L., Leipold, H.W., 1984. The toxicity and biotransformation of single doses of acetaminophen in dogs and cats. Toxicol Appl Pharmacol 74, 26–34. https://doi.org/10.1016/0041-008x(84)90266-7

  49. Schlesinger, D.P., 1995. Methemoglobinemia and anemia in a dog with acetaminophen toxicity. Can Vet J 36, 515–517.

  50. Schweizer, A., Brom, R., 1985. Differentiation of peripheral and central effects of analgesic drugs. Int J Tissue React 7, 79–83.

  51. Schwenk, W.F., Kahl, J.C., 1996. Acetaminophen glucuronidation accurately reflects gluconeogenesis in fasted dogs. Am J Physiol 271, E529-534. https://doi.org/10.1152/ajpendo.1996.271.3.E529

  52. Serrano-Rodríguez, J.M., Mengual, C., Quirós-Carmona, S., Fernández, J., Domínguez, J.M., Serrano-Caballero, J.M., Morgaz, J., Navarrete-Calvo, R., Gómez-Villamandos, R.J., Granados, M.D.M., 2019. Comparative pharmacokinetics and a clinical laboratory evaluation of intravenous acetaminophen in Beagle and Galgo Español dogs. Vet Anaesth Analg 46, 226–235. https://doi.org/10.1016/j.vaa.2018.09.042

  53. Sikina, E.R., Bach, J.F., Lin, Z., Gehring, R., KuKanich, B., 2018. Bioavailability of suppository acetaminophen in healthy and hospitalized ill dogs. J Vet Pharmacol Ther 41, 652–658. https://doi.org/10.1111/jvp.12664

  54. Smolarek, T.A., Higgins, C.V., Amacher, D.E., 1990. Metabolism and cytotoxicity of acetaminophen in hepatocyte cultures from rat, rabbit, dog, and monkey. Drug Metab Dispos 18, 659–663.

  55. St Omer, V.E., Mohammad, F.K., 1984. Effect of antidotal N-acetylcysteine on the pharmacokinetics of acetaminophen in dogs. J Vet Pharmacol Ther 7, 277–281. https://doi.org/10.1111/j.1365-2885.1984.tb00912.x

  56. Stewart, J.E., Haslam, A.K., Puig, J., 2016. Pathology in Practice. Acetaminophen (paracetamol) toxicosis. J Am Vet Med Assoc 248, 1009–1011. https://doi.org/10.2460/javma.248.9.1009

  57. Sussman, N.L., Chong, M.G., Koussayer, T., He, D.E., Shang, T.A., Whisennand, H.H., Kelly, J.H., 1992. Reversal of fulminant hepatic failure using an extracorporeal liver assist device. Hepatology 16, 60–65. https://doi.org/10.1002/hep.1840160112

  58. Swales, J.G., Temesi, D.G., Denn, M., Murphy, K., 2012. Determination of paracetamol in mouse, rat and dog plasma samples by laser diode thermal desorption--APCI-MS/MS. Bioanalysis 4, 1327–1335. https://doi.org/10.4155/bio.12.68

  59. Tams, T.R., 1984. Management of liver disease in dogs and cats. Mod Vet Pract 65, 107–114.

  60. Teraoka, H., 2014. [Current understanding of differential sensitivity of animals to toxic substances: species, strain and individual differences]. Chudoku Kenkyu 27, 314–319.

  61. Villar, D., Buck, W.B., Gonzalez, J.M., 1998. Ibuprofen, aspirin and acetaminophen toxicosis and treatment in dogs and cats. Vet Hum Toxicol 40, 156–162.

  62. Wallace, K.P., Center, S.A., Hickford, F.H., Warner, K.L., Smith, S., 2002. S-adenosyl-L-methionine (SAMe) for the treatment of acetaminophen toxicity in a dog. J Am Anim Hosp Assoc 38, 246–254. https://doi.org/10.5326/0380246

Expert Opinion

  1. 1317822  Extrapolation of pharmacological properties in man and veterinary species. Some material employed in collating the data displayed here was taken from veterinary product datasheets or extrapolated from pharmacology texts.


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