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Metronidazole Neurotoxicity in Dogs

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Metronidazole neurotoxicity in dogs is something dog owners should be aware of considering its seriousness. As with other medications, there can be risks for adverse effects and this form of toxicity affecting the dog's nervous system can be one of them. Fortunately, it is not very common, but knowledge is power and therefore a knowledgeable owner will know what may be happening to their canine companion. A missed diagnosis can prove to be deleterious, leading to a previously healthy dog's deterioration and death. 

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Metronidazole Use in Dogs 

Metronidazole is a strong, prescription-only antibiotic. More popularly known by its brand name Flagyl, metronidazole is widely used in veterinary medicine despite the fact that it lacks FDA approval for veterinary use.

As an antibiotic, metronidazole is commonly used to treat anaerobic bacterial infections and protozoal infections. It's often used to treat infections with giardia, trichomonas, entamoeba and balantidium.

Because of its anti-inflammatory and immune-modulating properties when inside the bowels, it can also be used to treat inflammatory conditions in the intestines. Metronidazole is indeed frequently used to treat colitis (inflammation of the colon) and enterotoxemia caused by Clostridium perfringens. Flagyl is also used for treating dog diarrhea of undetermined origin, pancreatic insufficiencies followed with small intestines bacterial overgrowth, tetanus and liver disease related complications.

When used in combo with corticosteroids, metronidazole can help successfully treat inflammatory bowel syndrome and gum inflammations. Topical metronidazole formulations can be used to treat skin infections.

Last but not least, unlike most drugs, metronidazole can penetrate the blood-brain barrier which makes it suitable for treating certain types of central nervous system infections.

Metronidazole is available in the form of oral tablets, capsules and liquid suspensions. It is also available in the form of injectable solution and topical gel. Because of the drug’s bitter taste, the oral forms are relatively hard to administer in dogs, but lately manufacturers are add different flavoring compounds to make the pills more palatable.

Once introduced in the organism, metronidazole is rapidly absorbed from the gastrointestinal tract and transferred in the liver. Inside the liver, metronidazole is metabolized and then its by-products are excreted through the feces and urine.

Metronidazole takes effect within 1 to 2 hours of administration. Its effects cannot be noticed immediately. However, gradual improvement should be expected after few days of use.

Metronidazole Neurotoxicity in Dogs

While metronidazole has a wide margin of safety, it can lead to potential side effects and toxicity. Neurotoxicity is mostly observed with chronic, extended use in dogs that have received weeks to months of therapy. In general, metronidazole treatment should not exceed 10 days (according to the instructions found in the manufacturer’s leaflet).

Dogs with underlying liver issues are more likely to be affected.

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There used to be belief that this form of toxicity was seen with significantly high doses, but according to a 2018 study conducted by the Australian Veterinary Association, signs of neurotoxicity in dogs were sometimes noticed at much lower doses than previously reported. The study emphasizes the importance of therefore using caution when prescribing metronidazole at doses over 40 mg/kg every 24 hours, regardless of the duration of the treatment.

In humans, metronidazole neurotoxicity caused classical tell-tale lesions in the cerebellum that are visible on an MRI, with the lesions particularly affecting the cerebellar dentate nuclei. Signs suggestive of metronidazole neurotoxicity in dogs involve the central nervous system and include the following neurological signs:

  • Disorientation
  • Staggering gait
  • Side-to-side eye movement
  • Dilated pupils
  • Head tilt
  • Conscious proprioceptive deficits
  • Low heart rate
  • Lack of muscle control
  • Muscle spasms
  • Joint knuckling
  • Stiffness
  • Tremors
  • Seizures

The best way to diagnose metronidazole toxicosis is by administering diazepam intravenously. Namely, the diazepam causes an immediately visible but transient improvement of the clinical signs.

Treatment of Metronidazole Neurotoxicity in Dogs

The treatment of metronidazole neurotoxicity in dogs includes:

  • Discontinuation of the drug – because of the drug’s relatively short half-life, the organism gets rid of the drug and the neurological signs start to diminish quickly. However, it may take between several days to up to 2 weeks for the neurological signs to disappear completely.
  • Limiting absorption in acute overdoses using standard protocols. Extreme caution should be used before attempting to induce vomiting in dogs showing central nervous system signs due to these risks for aspiration.
  • Diazepam administration – the diazepam is administered orally every 8 hours usually for about 3 days. Diazepam alleviates the neurological symptoms thus shortening the recovery period.
  • Fluid therapy – to keep the dog well hydrated and nutritionally satiated, fluid therapy also helps flush the kidneys thus promoting faster metronidazole elimination.
  • Symptomatic and supportive care – individually tailored based on the patient’s needs.

For proper observation and treatment, dogs with metronidazole neurotoxicity should be hospitalized for at least 24 hours. However, the exact length of the hospitalization period depends on the severity of the clinical manifestation and the patient’s response to treatment.

According to a study, dogs administered diazepam recovered more quickly. In 21 dogs, the recovery time was 38 hours in those treated with diazepam versus 11 days in the untreated ones (Evans et al. 2003) All in all, the recovery period can be sometimes long but fortunately, long-lasting complications are extremely rare.

"The neurologic adverse effects of metronidazole are well documented in humans and companion animals. There is currently no recommended treatment other than withdrawing the drug and providing supportive care. "~(Evans et al. 2003)

References:

Evans J, Levesque D, Knowles K, Longshore R, Plummer S (2003): Diazepam as a treatment for metronidazole toxicosis in dogs: a retrospective study of 21 cases. Journal of Veterinary Internal Medicine 17, 304–310.

Plumb's Veterinary Drug Handbook: Desk By Donald C. Plumb

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