Pharmacotherapeutics in Reptiles

[El Lobo]

Pharmacotherapeutics in Reptiles: An Update and Review
James W. Carpenter, MS, DVM, DACZM
Professor of Zoological Medicine, Department of Clinical Sciences, College of Veterinary Medicine, Manhattan, KS, USA

Introduction

Although a modest number of pharmacokinetic studies have been conducted on reptiles, they are really quite limited when one considers all the drugs that are used to treat many of the extant 7500 species of this extremely diverse class of animals. Drugs with available pharmacokinetic data should be selected when possible. With the extreme variations noted within Class Reptilia, it is not surprising to find variations in the effectiveness of certain drugs, or toxicities of others, when one attempts to extrapolate from one species to another. Although there are limitations to metabolic scaling, it can be a useful tool for some drugs when no pharmacokinetic data are available. However, it should be noted that the reptilian resting metabolic rate is 1/10 to 1/3 lower than the resting oxygen consumption rate of mammals of an equivalent size.

Because sick reptiles may not absorb drugs well, it is important to correct hypothermia (try to maintain a preferred optimum temperature zone), other suboptimal environmental conditions, dehydration, malnourishment (hypoglycemia), and electrolyte imbalance concurrent to administration of therapeutic agents. This is especially important when using nephrotoxic and hepatotoxic drugs.

Like other lower vertebrates, reptiles have a renal portal system as a unique component to the circulatory system. Although reports exist of nephrotoxicosis associated with the administration of aminoglycosides, it appears that the toxicosis was attributed to high doses of gentamicin rather than the route of administration. This plus recent research suggests that parenteral administration of drugs into the caudal extremities may not pose as great a risk as once thought.2 It still may be prudent, though, to avoid administering potentially nephrotoxic drugs into the tail or caudal extremities.

Antibiotics

Antimicrobial therapy is an important part of medically managing reptiles with infectious diseases. Selection of specific chemotherapeutics is more difficult than in mammals because of the broad range of behavioral, anatomic, and physiologic peculiarities of the various species within the Class Reptilia.

Culture results should be correlated with the response to treatment. Therapeutics can be selected or modified based on the isolate and sensitivity data. Two areas of the culture results must be evaluated: the quantitative results and the minimum inhibitory concentrations (MIC) patterns. Other factors to consider when selecting an antimicrobial is the species being treated, physical condition of the patient, frequency of administration, cost of the therapy, and owner compliance.

Most bacterial pathogens of reptiles, and many of these could be part of the host's normal flora, becoming pathogenic when the host is immunosuppressed or stressed. Also, the presence of gram-negative bacteria on culture does not always indicate pathogenicity, and mixed infections are common. Gram-negative bacteria that are most commonly isolated from reptiles include: Aeromonas, Klebsiella, Morganella, Pseudomonas, Provendencia, and Salmonella. Also, anaerobic infections are quite common (yet some of the most frequently used antibiotics in reptiles, fluoroquinolones and aminoglycosides, are not effective against anaerobes). Antibiotics should not be used indiscriminately in reptiles because of the risk of creating antimicrobial resistant organisms.

Following are the antibiotics commonly used in reptile medicine:

Extended-spectrum penicillins (carbenicillin, piperacillin): gram-negative bacteria

Third-generation cephalosporins (cefotaxime, ceftazidine): broad-spectrum, but primarily gram-negative bacteria

Macrolides (azalide: azithromycin): broad-spectrum antibacterial, Chlamydophila, Mycoplasma

Tetracyclines (doxycycline): spectrum vs. Chlamydophila, Mycoplasma, and rickettsial organisms; broad-spectrum

Chloramphenicol (chloramphenicol, broad-spectrum bacteriostatic; florfenicol, broad-spectrum bacteriocidal)

Lincosamides (clindamycin, gram-positive bacteria and anaerobes)

Aminoglycosides (amikacin, gram-negative bacteriocidal)

Nitroimidazole (metronidazole, cidal vs. selected protozoans and most obligate anaerobes)

Trimethoprim-sulfa (trimethoprim-sulfadiazine and -sulfamethoxazole, this synergism is bacteriocidal, broad-spectrum)

Fluoroquinolones (enrofloxacin, marbofloxacin; bacteriocidal with activity vs. both gram-negative and gram-positive pathogens; limited spectrum vs. anaerobes)

Combination therapy (i.e., aminoglycoside and an extended-spectrum penicillin) are often very effective in the treatment of retiles. The Exotic Animal Formulary (2005) lists the antimicrobial, antiviral, antifungal, antiparasitic, and analgesic agents used in reptiles.

AIPMMA Beads

Antibiotic-impregnated polymethylmethacrylate (AIPMMA) beads are an effective means of delivering an antibiotic in an infected area in which tissue integrity and vascular supply have been compromised. The beads are placed in an infected lesion after surgical debridement. Tissue fluids penetrate the bead, and the antibiotic is eluted into the lesion in high concentrations over weeks to months.

In reptiles, AIPMMA beads are used to provide controlled, local release of antimicrobials for the treatment of infection (generally osteomyelitis or abscesses). In addition, local release is associated with a lower risk of toxicosis than parenteral administration. Also, effective concentrations of antimicrobials can be achieved and maintained even if the site of infection is difficult to reach, and AIPMMA beads can be used to help manage infections in intractable animals in which systemic administration may be difficult. The beads are reasonably easy to make, and may be sterilized with ethylene oxide gas.

The ideal antimicrobial for incorporation in an AIPMMA bead would be bactericidal, have a broad spectrum of activity, and be effective at low concentrations; have low tissue toxicity; be heat stable (up to 100°C); have high water solubility; and results in low serum concentrations but high concentrations in adjacent bone and soft tissue. Ideally, the antibiotic should come as sterile powder. Liquid antibiotics have been used, but they may reduce the mechanical strength of the PMMA. It is best to leave the beads in until the site is no longer infected, and then to remove them. Some of the antibiotics which have been used include amikacin and ceftiofur.

Analgesics

Although there are few studies evaluating the use of analgesics for pain in reptiles, it is strongly recommended that an analgesic be administered before (preemptive analgesia) any painful procedures or whenever an animal may be in pain. As with other animals, the consequences of untreated pain are consistent with impaired homeostasis and may impair the immune system and inhibit healing.

The two major classes of analgesic drugs in reptiles are opioids (butorphanol, buprenorphine) and, more commonly, nonsteroidal anti-inflammatory drugs (NSAIDs) (meloxicam, carprofen, ketoprofen, and flunixin meglumine [if the latter is used, administer for maximum of 3 days]). Of these, butorphanol, carprofen, and meloxicam are the most commonly used. In a study in green iguanas, meloxicam at 0.2 mg/kg IV or IM lasted approximately 36 hours (author suggests that 0.4 mg/kg PO q48h may be effective).

There are very few investigations that describe the assessment of opioids and none that evaluate the efficacy of NSAIDs in reptiles. The unknown actions of opioids and NSAIDs in the central nervous system of reptiles, therefore, may result in unpredictable variations in the duration, potency, and side effects of these drugs when the doses are determined by extrapolation from mammalian doses. Until more studies on the effects of NSAIDs in reptiles are performed, it is probably best to consider the possibility that side effects (gastrointestinal irritation, renal compromise, and platelet inhibition) similar to those seen in mammals may also occur in reptiles (Mosley). Therefore, hydration status, concurrent medications (steroids), gastrointestinal disease, and renal disease should be addressed before administering these drugs.

Therapeutic Contraindications

Although there are far fewer reports of therapeutic contraindications in reptiles than for other species, they can occur.5 For example, ivermectin toxicity can occur in chelonians where, even at low dosages, it can result in paresis and death. A dose considered safe in one chelonian species may not be safe in another.

Metronidazole is used to treat anaerobic bacterial and protozoan diseases in reptiles. Tortoises may develop side effects (anorexia, head tilt, circling, disequilibrium, and signs of hepatotoxicity) from this drug and may not tolerate the relatively high doses or duration of therapy necessary to treat some conditions (i.e., amoebiasis).4 Metronidazole treatment regimens in chelonians need to be tailored to the individual with close monitoring for clinical signs of toxicity. Metronidazole toxicity has also resulted in the deaths of indigo snakes and California and Arizona Mountain king snakes when doses of more than 100 mg/kg were used and in uracoan rattlesnakes at doses greater than 40 mg/kg.

References

1. Carpenter JW (ed.). Exotic Animal Formulary. 3rd ed. St. Louis, Elsevier Publishers, 2005. Pp 53-131, 547-554.

2. Mitchell MA. Therapeutics. In: Mader DR (ed.). Reptile Medicine and Surgery. 2nd ed. St. Louis, Elsevier Publishers, 2006. Pp. 631-664.

3. Mosley CAE. Anesthesia and analgesia in reptiles. Semin Avian Exotic Pet Med 14(4): 243-262, 2005.

4. Norton TM. Chelonian emergency and critical care. Semin Avian Pet Med 14(2): 106-130, 2005.

5. Rosenthal KL. Therapeutic contraindications in exotic pets. Semin Avian Exotic Pet Med 13(1): 44-48, 2004.

[Raven_Vivi]

Interesting read ;D
I'm taking pharmcokinetics and pharmcotherapy this coming fall so maybe I'll have some interesting things to say later ^^