Today is the first day of Fall 2020!
In honor of this awesome season, I thought we'd talk about another type of fall...vestibular disease! :)
How Does Metronidazole Cause Vestibular Signs?
It is not 100% certain, but it appears that modulation of GABA at the level of the cerebellum is involved. Stay with me...!! GABA is an inhibitory neurotransmitter and there is LOADS of GABA in the cerebellum because it is a largely inhibitory part of the brain. (I like to think of the cerebellum as my mother. As a mother, my job is to "modulate" the activity of my children so they don't get hurt! When you take a step, I tell you how far, how wide, etc. so that you don't trip on a stair. See my point?) Okay, so if the cerebellum is inhibitory to movement, and you remove inhibition, movement gets exaggerated. (Hypermetria, intention tremors, truncal sway!) The cerebellum helps to keep balance in check as well via various mechanisms. Getting back to metronidazole, if we inhibit GABA, then actions become more exaggerated.
Signs of Metronidazole Toxicity
DOG: Signs of cerebellovestibular disease including head tilt, nystagmus, positional strabismus, truncal sway, hypermetria, intention tremor.
CAT: Okay, cat's don't play by the rules. They show forebrain signs such as seizures, blindness and mentation changes. Let's not talk about cats today, okay?
Diagnosis of Metronidazole Toxicity
This is both an easy one, and a hard one. There isn't a specific "test" used to make the diagnosis. However, with a history of ANY DOSE of metronidazole within the last 12 hours, one might consider metronidazole toxicity. I have seen several dogs that received metronidazole historically without trouble and developed signs of toxicity on subsequent dosing. I also have seen signs of toxicity at the first dosing sequence at standard doses. It is more likely at higher doses (60 mg/kg/day) but do not exclude the possibility at lower doses.
Treatment for Metronidazole Toxicity
Stop metronidazole administration! Additionally, you can administer diazepam at 0.1-0.5 mg/kg PO q8hr for several days. Why diazepam? I'm glad you asked! Diazepam is a GABA agonist, therefore it confers more inhibition to the cerebellum. Dogs receiving oral diazepam recovered in 1.5 days compared to untreated dogs that recovered in 11 days. (Evans J, et al. JVIM 2003; 17(3):304-310.) I routinely prescribe diazepam for pets with suspected metronidazole toxicity as a result of this study.
Whew it has been busy lately!! I hope you are doing well and staying safe. I appreciate what you do to help clients and their pets. Let me know how I can help you manage your patients with neurologic disease.
On site consultation is available Monday through Saturday at variable times throughout the week. Email consults are completed in evenings.
Have a good week!