First, just a general comment that does not specifically refer to this case.  We  have seen over the years that pergolide dose does have to be steadily increased.  This could be due to the horse's body metabolizing it more efficiently over time.  It could also be due to the pituitary growth continuing to expand because the dosage or dosage frequency is not sufficient to suppress it.  We don't know.

With extremely high doses and rapidly escalating doses, there may be another factor.  Pergolide mimics the effects of dopamine.  When dopamine or any other neurotransmitter or hormone is present in very high levels, the receptors for it are downregulated, meaning the receptors are withdrawn from the cell surface so the hormone, neurotransmitter or drug will not produce an effect because it can't bind to the cell.  This is known to happen with pergolide:

Chronic levodopa or pergolide administration induc... [Neurology. 1984] - PubMed - NCBI

 

Is there a specific dose where this happens, when high pergolide levels start to cause receptors to go internally so that it no longer has the desired effect?  We don't know, but there probably is.

Another possibility that can never be forgotten is that the compounded drug was compromised and is not as potent as it should be.  You may be handling the product correctly but it could be the tail end of a shipment to the compounder that expires while you have, or could have been damaged in transport by things like high temperatures in trucks during transport.

Stormy is a complicated case.  While I don't doubt at all that poor appetite can be one of her symptoms of poor control, there are other possible causes and it's really not a reliable indicator of need for more pergolide.  Even in November 2013 when her ACTH was in the teens she still had issues with appetite, foot comfort and eye drainage.

The only thing that has made a clear and dramatic improvement in her appetite is adding yeast and for hoof comfort only NSAIDs or nerve blocks.

Because of all the unknowns, I don't know if you can really sort out what is going on here but this is what I would try:

- Repeat ACTH on the current dose

- Get fresh pergolide from another pharmacy

- If no change in ACTH or higher, drop the dose to 13.5 to 14 mg and repeat ACTH in 3 weeks

- Continue other support of ultra low ESC/starch diet and meticulous hoof trimming

I would also strongly suggest you do a complete chemistry blood panel which will show up any issues with organ function.  Not so much concerned about the pergolide for this as for the long course of Previcox and also her age.  This should really be done yearly at least.

Eleanor in PA

www.drkellon.com

EC Co-owner

Feb 2001