Sea Turtle Analgesics Selection - NSAIDS. Loggerhead Coquina (postoperative ketorolac)

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Clifford Gaines
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1 Sea Turtle Analgesics Selection - NSAIDS Craig A. Harms, D.V.M., Ph.D, Dipl. ACZM North Carolina State University Loggerhead Coquina (postoperative ketorolac) $&

Sources of Information!! Anecdote!! Expert consultation!! Extrapolation!! Metabolic Scaling!! SMEC = K(W -0.25 )!! K = 10 for reptiles!

! Ceftazidime, Florfenicol!! Stamper et al. 1999, Stamper et al. 2003, Innis et al. 2011!! Fluconazole!! Mallo et al.

! Meloxicam!! Claus et al. 2007 (Proc IAAAM), Soloperto et al. 2011 (ISTS)!! Oxytetracycline!! Harms et al. 2004!! Ticarcillin!

2 Sources of Information!! Anecdote!! Expert consultation!! Extrapolation!! Metabolic Scaling!! SMEC = K(W )!! K = 10 for reptiles!! Formularies!! Pharmacokinetic Studies!! Gold standard!! Pitfalls with the gold standard Pharmacokinetic Studies in Sea Turtles!! Ceftazidime, Florfenicol!! Stamper et al. 1999, Stamper et al. 2003, Innis et al. 2011!! Fluconazole!! Mallo et al. 2001, Innis et al. 2011!! Itraconazole!! Manire et al. 2001!! Praziquantel, Enrofloxacin!! Jacobson et al. 2002, Jacobson et al. 2005!! Meloxicam!! Claus et al (Proc IAAAM), Soloperto et al (ISTS)!! Oxytetracycline!! Harms et al. 2004!! Ticarcillin!! Manire et al. 2005!! Danofloxacin!! Marin et al. 2005!! Marbofloxacin!! Lai et al. 2009!! Clindamycin!! Harms et al. 2011!! Tramadol!! Norton et al (ISTS)!&

3 Selected Studies Relevant to Sea Turtle Analgesia!! Baker BB, Sladky KK, Johnson SM Evaluation of the analgesic effects of oral and subcutaneous tramadol administration in red-eared slider turtles. J Am Vet Med Assoc 238: !! Clauss T, Papich MG, Coy S, Hernandez-Divers S, Berzins IK, Budsberg SC Pharmacokinetics of meloxicam in loggerhead sea turtles (Caretta caretta) after single dose intravenous administration. Proc IAAAM, 228.!! Divers SJ, Papich M, McBride M, Stedman NL, Perpinan D, Koch TF, Hernandez SM, Barron H, Pethel M, Budsberg SC Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas (Iguana iguana). Am J Vet Res 71: !! Norton TM, Sladky KK, Cox S, Nelson S, Kaylor M, Hupp A. Thomas R Pain management strategies in sea turtles and pharmacokinetics of tramadol and O-desmethyltramadol in loggerhead sea turtles (Caretta caretta). ISTS 2013.!! Royal LW, Lascelles BX, Lewbart GA, Correa MT, Jones SL Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles (Terrapene carolina carolina). J Zoo Wildl Med 43: !! Sladky KK, Mans C Clinical analgesia in reptiles. J Exot Pet Med 21: !! Sladky KK, Miletic V, Paul-Murphy J, Kinney ME, Dallwig RK, Johnson SM Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles. J Am Vet Med Assoc 230: !! Soloperto S, Di Bellow A, Lai OR, Freggi D, Tinelli A, Carofiglio V, Crescenzo G Pharmacokinetic behavior of meloxicam in loggerhead sea turtle (Caretta caretta). ISTS 2011.!! Tuttle AD, Papich M, Lewbart GA, Christian S, Gunkel C, Harms CA Pharmacokinetics of ketoprofen in the green iguana (Iguana iguana) following single intravenous and intramuscular injections. J Zoo Wildl Med 37: COX Inhibition NSAIDS!! Cyclooxygenase (COX) = prostaglandinendoperoxide synthase (PTGS)!! Synthesis of prostaglandins, prostacyclin, thromboxane!! Inflammation, maintenance of gastric epithelium, kidney and platelet/ thrombocyte function!! Nonsteroidal Anti-Inflammatory Drugs inhibit COX enzymes '&

4 COX Selectivity!! Mammal paradigm:!! COX-1, constitutive, tissue maintenance!! COX-2, inducible, inflammation!! Nonselective and Selective NSAIDS!! Potential adverse effects: GI ulceration, renal crest necrosis, liver damage, impaired hemostasis!! Avoid concurrent use with aminoglycosides (e.g. amikacin)!! Box turtles COX-1 induced to greater extent than COX-2 in traumatized muscle!! Royal et al Analgesia NSAIDS!!!"#$%&%$'()*"#(%$)'+,-'(*./*'01'2$3)'!! -'(*./*'456'7))$'56623%58)9':%84'4)(2;;45*%3')$8);%8%6'5$9'9)584'%$' C)82B;2D)$'E'(*./*'01'F'EG'4'#B'82'H'9'!! %*#5$56'845$'%$'92*6'!! 1)"2&%35('+,-'K'+,E'(*./*'01'!! %$'"2**);4)596'845$'%$'92*6'M7#8'5"62'6"2:')"%(%$58%2$'%$'%*#5$56N'!! C)82;2"53'8;2()845(%$)'+,EH'(*./*'01'F'EG'4'#B'82'H'9'!! OJ$)/)$')8'5",'E++PA'C)""J')8'5",'E++HA'Q#88")')8'5",'E++PA'153R)5$')8'5",'E++SA'>"5#6')8' 5",'E++TA'U5)*);')8'5"'E++VA'Soloperto et al '' (&

5 Analgesia opioid extrapolation!! Butorphanol (?) mg/kg IM or SC!! Failed to affect thermal withdrawal latencies in red-eared sliders at 2.8 or 28 mg/kg, and depressed ventilation for 1 2 hr at 28 mg/kg!! Morphine 1.5 mg/kg!! Increased thermal withdrawal latencies in red-eared sliders by 8 hr for at least 24 hr, but depressed ventilation at least 4 hr!! Mixed hepatic (gluronidation) and renal excretion!! Tramadol 5 10 mg/kg PO!! Increased thermal withdrawal latencies with less respiratory depression than for morphine!! extensively metabolized by several metabolic pathways Plumb L"59/J')8'5",'E++TA'W5/);')8'5",'E+--' %&

6 Local Anesthetics!! Lidocaine (1 2 mg/kg; < 5 mg/kg); Buprenorphine (1 mg/kg; < 2 mg/kg)!! Sladky & Mans JEPM 21: !! +/- sedation with midazolam 2 3 mg/kg IV!! Harms et al JZWM 45: #&

POST-OPERATIVE ANALGESIA AND FORMULARIES

POST-OPERATIVE ANALGESIA AND FORMULARIES An integral component of any animal protocol is the prevention or alleviation of pain or distress, such as that associated with surgical and other procedures. Pain