scott@vtx-cpd.com

Hey Tessa!

Keep asking questions. This is a great question!

So, ranitidine is a funny one. Despite its poor gastric acid modifying effect, some beaople use it due to the possible pro-kinetic effect.

There is a agood RCVS review atricle on this:

file:///C:/Users/skilpatrick/OneDrive%20-%20IDEXX/Downloads/357-Article%20Text-4095-3738-10-20210212.pdf

“The vast majority of the evidence investigating ranitidine as a prokinetic has been carried out in experimental
settings both in vivo with healthy conscious and anaesthetised dogs and in vitro. Under these circumstances
ranitidine has shown some prokinetic properties. However, it is difficult to translate these results into reliable
clinical recommendations, as the doses mentioned in these studies are often higher than the ones clinically
recommended and healthy canine patients might respond differently to clinically affected ones

Conclusion
Although in experimental settings ranitidine has shown some prokinetic activities, no reliable clinical
recommendations can be drawn from the appraised studies. There is a need of prospective clinical trials
evaluating the administration of ranitidine to dogs presenting with GI hypomotility. Until further relevant
studies become available, the efficacy of ranitidine administration as a prokinetic agent in dogs with GI
hypomotility remains uncertain.”

Honestly, I have used it for this purpose in the past, but rarely do now.

Hope that helps.

Scott 🙂

Hello everyone.

I hope you are well. It is an interesting drug. I have no direct experience of using it.

This is probably the most useful paper discussing the drug:

Safety and effectiveness of the sodium-glucose cotransporter inhibitor bexagliflozin in cats newly diagnosed with diabetes mellitus

Michael J. Hadd, Stephen E. Bienhoff, Susan E. Little, Samuel Geller, Jennifer Ogne-Stevenson, Thomas J. Dupree, J. Catharine Scott-Moncrieff

Abstract

Background
Bexagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. A pilot study has shown that bexagliflozin can decrease dependence on exogenous insulin in cats with diabetes mellitus (DM).

Objective
To evaluate the safety and effectiveness of bexagliflozin as a monotherapy for DM in previously untreated cats.

Animals
Eighty-four client-owned cats.

Methods
Historically controlled prospective open-label clinical trial. Cats were dosed PO with 15 mg bexagliflozin once daily for 56 days, with a 124-day extension to evaluate safety and treatment effect durability. The primary endpoint was the proportion of cats experiencing a decrease in hyperglycemia and improvement in clinical signs of hyperglycemia from baseline on day 56.

Results
Of 84 enrolled cats, 81 were evaluable on day 56, and 68 (84.0%) were treatment successes. Decreases in mean serum glucose, fructosamine, and β-hydroxybutyrate (β-OHB) concentrations were observed, and investigator assessments of cat neurological status, musculature, and hair coat quality improved. Owner evaluations of both cat and owner quality of life were favorable. The fructosamine half-life in diabetic cats was found to be 6.8 days. Commonly observed adverse events included emesis, diarrhea, anorexia, lethargy, and dehydration. Eight cats experienced serious adverse events, 3 of which led to death or euthanasia. The most important adverse event was euglycemic diabetic ketoacidosis, diagnosed in 3 cats and presumed present in a fourth.

Conclusion and Clinical Importance
Bexagliflozin decreased hyperglycemia and observed clinical signs in cats newly diagnosed with DM. As a once-daily PO medication, bexagliflozin may simplify the management of DM in cats.

I certainly do not think this can be considered a substitute for insulin, but may be helpful in some cases. As far as I am aware, not currently avaiable in the UK.

Scott 🙂

Hopefully that helps!

Let me know if you have any other questions.

Scott 🙂

Hello Victoria.

I hope you are well. We chatted about this over on the ECC corse. I will pop that conversation here:

Q: If I understood correctly, you do plasma transfusions in septic patients as plasma helps repairing the glicocalix?

A: Great question about glycocalyx, gotta love it!! Yes I think you understood this correctly.
I replied to this before but never posted it so hope for better luck this time! Will also wait and see what Kerry replies but I can share the two reasons why I may use plasma in septic patients 🙂

The first one would be as a fluid therapy of choice as “crystalloid sparring”. So typically the septic patients that have septic peritonitis and are having large fluid losses through high protein abdominal exudates will have hypoproteinaemia and decreased COP. Normally they do require large volume of fluid to resuscitate them so I would use plasma to provide some oncotic support, allow me to use smaller volume of fluids and not use as much crystalloids that I know would damage the glycocalyx further, and would worsen the TP/alb/COP and potentially cause interstitial oedema and other issues.

The second one is the glycocalyx.
So as you know the glycocalyx is a thick negatively charged carbohydrate rich layer that coats the vascular endothelium. Under physiological conditions, positively charged soluble components like plasma proteins and water are trapped in the glycocalyx forming an extended endothelial surface layer.

The glycocalyx has a lot of functions specifically it is a barrier between blood and vessel wall, it maintains blood fluidity by modulating interactions with endothelium with blood cells and proteins and regulates cell adhesion and vascular permeability. Also creates a high intravascular colloid osmotic gradient and acts as a mechano-transducer (so it is super clever and when it senses shear stress and will then induce as a response endothelial release of nitric oxide to counteract this).

Shedding of the endothelial glycocalyx components has been proven to happen in response to ischaemia and hypoxia, secondary to ROS, inflammation and sepsis as well as trauma (specifically haemorrhagic shock).

Animal model studies have shown that resuscitation with plasma partially restores it whilst crystalloids such as lactated ringers do not, and neither do synthetic colloids like hydroxyethyl starch.
We think this is due to the albumin in the plasma that preserves the endothelial integrity as provision of albumin will attenuate glycocalyx shedding and reduce interstitial oedema in other animal models. It may also be because albumin can attenuate neutrophil adhesion to endothelium, and it has other anti-inflammatory properties. There may be other components in the plasma, howeverm that also help protect or restore the glycocalyx in plasma…. lots of studies still on-going! I reckon that glycocalyx resuscitation is something we will be useing in the not so distant future :)!

If you want some papers on this I would suggest:
Rahbar MH, del Junco DJ, Huang H, Ning J, Fox EE, Zhang X, et al. A latent class model for defining severe hemorrhage: experience from the PROMMTT study. J Trauma Acute Care Surg (2013) 75(1 Suppl 1):S82–8

Holcomb JB, del Junco DJ, Fox EE, Wade CE, Cohen MJ, Schreiber MA, et al. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg (2013) 148(2):127–36

Pati S, Matijevic N, Doursout MF, Ko T, Cao Y, Deng X, et al. Protective effects of fresh frozen plasma on vascular endothelial permeability, coagulation, and resuscitation after hemorrhagic shock are time dependent and diminish between days 0 and 5 after thaw. J Trauma (2010) 69(Suppl 1):S55–63

Schott U, Solomon C, Fries D, Bentzer P. The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review. Scand J Trauma Resusc Emerg Med (2016)

Hello everyone!

This was a great session where Yvonne and I played endocrinology bingo!

Hope you enjoy watching it back!

Scott 🙂