Despite a nominal understanding of reptile analgesia, it has been shown that morphine, a µ-opioid receptor agonist, desensitizes the response to noxious stimuli in various reptilian species.2,3,5 Fentanyl, a µ-opioid agonist with 75–100 times the potency of morphine, is formulated for use as a transdermal therapeutic system (TTS) and has recently been shown to absorb across the skin of prehensile-tailed skinks (Corucia zebrata).1 Snakes, which possess highly permeable skin, appear to be ideal candidates for effective transdermal analgesia.4
Fentanyl TTS (12 µg/h, Mylan Pharmaceuticals Inc., Morgantown, WV, USA) were applied to the cranial one-third dorsum of five ball pythons (Python regius) using the adhesive backing and staples. Specimens ranged in body weight from 1.26–1.99 kg. Cardiac blood samples were drawn for nine days, and plasma fentanyl concentrations determined at times T=0, 4, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, and 216 h using HPLC-mass spectroscopy. Measurable concentrations were achieved within 4 h. Minimum therapeutic concentrations, as defined in mammals as 1 ng/ml, were reached within 8 h and sustained throughout the study. The mean and maximum concentrations were substantially higher than those hypothesized to attain analgesia in mammals, suggesting the potential to utilize smaller dosages. Snakes exhibited less activity, but no adverse side effects were observed. All patches remained securely attached throughout the study. This study concludes the TTS system delivers quantifiable fentanyl levels in ball python plasma and could potentially serve as an alternative route for prolonged analgesia administration to snakes.
Supported by grants from the Columbus Zoo and Partners in Conservation (PIC) Fund and University of Wisconsin Merck-Merial Summer Scholars Research Program.
1. Gamble KC. Plasma fentanyl levels achieved after transdermal fentanyl patch application in prehensile-tailed skinks, Corucia zebrata. Journal of Herpetological Medicine and Surgery. 2008;18(3/4):81–85.
2. Kanui TI, Hole K. Morphine and pethidine antinociception in the crocodile. J Vet Pharmacol Therap. 1992;15:101–103.
3. Mauk MD, Olson RD, LaHoste GJ, et al. Tonic immobility produces hyperalgesia and antagonizes morphine analgesia. Science. 1981;213:353–354.
4. Panchagnula R, Stemmer K, Ritschel WA. Animal models for transdermal drug delivery. Methods Find Exp Clin Pharmacol. 1997;19(5):335–341.
5. Sladky KK, Miletic V, Paul-Murphy J, Kinney M, Dallwig R, Johnson SM. Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles (Trachemys scripta). J Am Vet Med Assoc. 2009;70(9):1072–1078.