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Flagyl

By Dmitry B. Vassiliev, DVM, PhD


Citation:

Vassiliev, D.B. (2002). Flagyl. Chameleons! Online E-Zine, September 2002. (http://www.chameleonnews.com/02SepVassiliev.html)


Flagyl

Not quite a miracle drug, but worth every pretty penny.

What is flagyl?

Flagyl is a brand name for the drug metronidazole, the active ingredient. Outside of the US, other brand names for the family of similar active ingredients (termed the 5-nitroimidazoles) include Metrogil, Trichopol, Entizil, Klion and a few tens of names more! Flagyl is produced by Rhone-Poulenc Rozer, and just may be the company's most popular product. Flagyl is the only drug preparation with metronidazol in the form of suspension (liquid). Other drug preparations are in the form of pill or solution for intravenous infusions and are not convenient in practice for reptiles.

The family of metronidazoles was discovered in 1955, and early on researchers focused on the drug that would be called Flagyl. Its first use was in humans, treating trichomonads, sexually transmitted protozoa, and the amoeba E. histolytica. Later on, its extremely broad spectrum against anaerobic (growing without air) protozoa and also anaerobic bacteria was appreciated. Flagyl is successful against many protozoa and amoeba as well as most anaerobic and some aerobic bacteria.

What it works against

Flagyl is absorbed readily after an oral dose. In humans, high concentrations are reached by one hour after dosing. The half-life in blood is about 8 hours, and it distributes throughout the body in all of the body water. Flagyl then penetrates effectively from blood into body tissues and fluids. It is ubiquitous, showing up in cerebrospinal fluid, semen, milk, saliva, and vaginal secretions. Most of a dose of flagyl is metabolized by the liver. Some of Flagyl's metabolites are excreted in feces, and some in urine. These are pigments, and can discolor the urine and feces with a reddish-brown hue. The discoloration occurs in some but not all humans taking Flagyl, and might occur in turtles on long-term treatment with high doses (anecdotal reports). Discoloration of urates or feces of chameleons treated with Flagyl haven't been reported to the best of our knowledge, but may occur following high doses.

The chemistry of Flagyl suggests that we can give a safe oral dose to a chameleon, and the drug will reach every nook and cranny, working against parasites in the GI tract as well as bacteria hidden in the reproductive tract and other tissues. It will reach infections in the brain, lungs, liver, kidney, heart, blood and bone. What makes Flagyl so good, however, also makes it deadly when overdosed. Despite its popularity for 4+ decades, new uses for Flagyl are being disovered even today. For example, six months ago a new paper reported excellent results in a clinical trial with humans suffering from periodontal disease.

How it works

Metronidazol is considered a prodrug because it must become activated in order to be effective. The activation involves donation of electrons, and it is in this step that Flagyl acts against protozoa and bacteria. Flagyl works to destroy their DNA and to suppress further synthesis of their DNA. The DNA of protozoa and bacteria is essential to their life and replication. When their DNA is destroyed, their life ceases and the infection is cured.

Dosages and application for chameleons

There are many therapeutic schemes and dosages for metronidazol in reptiles. Different dosages may be used against different parasites and bacteria but these dosages usually depend on empiric experience and even on personal preferences of different authors. Generally, dosages against protozoan parasites are high : 60-160 mg/kg. Against anaerobic infection, doses range from about 20-40 mg/kg. Some have used Flagyl as an appetite stimulant at 10-20 mg/kg. The efficacy of Flagyl as an appetite stimulant is debatable; try this only under the guidance of your veterinarian.

Not only dosage, but also frequency of dosing and length of therapy, are highly important and should be done under the supervision of a veterinarian. Dosages that are too high may cause a toxic reaction. Care must be taken as toxic dosages can be different for different species and individuals. Insufficient dosages will be ineffective. Resistance to Flagyl is rare in some species but may be more common in reptiles. Regardless, insufficient doses should be avoided as they will delay cure. One case of resistance was observed by me after I administered metronidazol in the dosage of 60 mg/kg daily for 5-7 days for treating monocercomonosis (a disease caused by flagellated protozoans) in green iguanas (Iguana iguana). I got a strongly resistant population of these parasites that were, within 12 days, resistant to dosages of 100mg/kg.

Try to resist the urge to give Flagyl empirically (based on practical experience without use of scientific methods). Importers may use a "shotgun technique" for treating all imports with fenbendazole (Panacur) and metronidazole. At the very least, work with your veterinarian to design a treatment program for new imports. There are many dosages and treatment schedules for Flagyl, and your veterinarian will help you determine the best strategy. If in doubt about the effectiveness (or lack of) of Flagyl based on empirical dosages and schedules, peruse the literature on both empirical and scientific approaches to treating imported Asian turtles. The source is found at the end of this article.

While a "shotgun" approach may be used safely by importers, always consult a veterinarian before using Flagyl to treat an infection. Treatment should be based on results of cultures and sensitivities, and if anaerobic cultures aren't available, guidance from an experienced veterinarian will be essential for efficacious treatment.

Adverse reactions

Metronidazol is capable of breaching the blood-brain barrier and it also can accumulate in the liver. If metronidazol goes through the blood-brain barrier in excessive dosages it may cause neurological disorders, namely, incoordination, lethargy, flaccid paralyses, non-typical postures, and -sometimes - death. For most reptiles one dosage of 400 mg/kg is toxic. Some species of reptiles (perhaps certain albinos and others) may be sensitive to dosages of only 100mg/kg. In depressed animals with impaired gastrointestinal absorption, metronidazol may accumulate to toxic levels within a few dosages. Long treatment courses may cause liver damage. Although there is mentioned in literature that such damages are reversible, I have observed signs of liver failure continuing for 3-4 months and poor appetite to go for more then 6 months.

Because of its effects on the nervous system and liver, lower dosages should be used in chameleons with known diseases involving the Central Nervous System and liver. The combination of Flagyl and alcohol makes humans quite sick; one should use caution when dosing chameleons with Flagyl and alcohol-based products. Large doses are carcinogenic in rodents, but its cancer-causing effects (if any) are unknown for reptiles. Mutations may occur in certain species of bacteria and mammals, so the drug has been contraindicated during the first trimester of pregnancy for all species. The risk to reptiles appears to be low.

While not an adverse effect, the cost of Flagyl can be addressed. The drug is expensive. Wholesale prices are hundreds of times higher than for other common drugs such as Panacur and Baytril. Veterinarians often must use a special compounding pharmacy that will custom-make a suspension of Flagyl in a tasty concoction (those who have taken Flagyl tablets know the bitter taste all too well). Do not think that your veterinarian is growing wealthy from your Flagyl purchases. However, those working with large numbers of animals requiring treatment (such as new imports) often weigh the cost benefit of Flagyl.

For information on treating Asian turtles with Flagyl:

Bonner, B.B. 2000. Chelonian therapeutics. Vet Clinics N Amer: Exotic Animal Practice
3(1):257-332




Dmitry B. Vassiliev, DVM, PhD


Dr. Dmitry B. Vassiliev D.V.M., PhD is the senior herpetologist at the Moscow Zoo in Russia. He is an ARAV member and has published many articles in Russian, Japanese, and German journals on topics such as captive breeding of elapid snakes, shiniasaurus, and a variety of pythons. In the last ten years he has worked in veterinarian support of reptiles particularily in the field of parasitology, comparative pathology, and surgery. His travels have led him from Irian Jaya to Mongolia to Europe.




 

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