Great, thank you so much and yeah, welcome everybody to to this webinar where we're switching the focus to more specific treatments that we have available for our intoxicated patients. And so we've seen this figure multiple times now throughout the series, and, it's important to bear in mind that whilst we're talking about the, the antidote section, which is sort of roughly mid-process here, that, as you said before, only a really small fraction of toxins do have an antidote available. And so giving one shouldn't really be that, that initial focus at the expense of patient assessment and stabilisation and decontamination and all of the other things that we've talked about so far.
But it is, whilst I've set this out as a very sort of stepwise process, of course, all of this sort of stuff is happening simultaneously and it's very reasonable to consider how we're going to source an appropriate antidote during the early stages of treatment, so we have it available when, when the time comes. So it's sort of an early consideration, even though it's not an immediate priority per se. And what are we talking about when we refer to antidotes?
Well, There's plenty out there. These are some of the more common antidotes that we might consider in, in our poisoned, patients. And in the interest of time, rather than trying to sort of very superficially do all of these, and not really cover any and do any justice, I thought we'd pick up on a few of the more kind of interesting ones.
And then as we said, there's a bit of a poll at the end to Let you guys kind of dictate what, what's sort of included next week. So when you're not included today, there's a chance to kind of vote for content in next week's webinar as well. But The things on here, there's, there's lots of intoxication for things patients can ingest in the, the home environment, obviously.
But you'll notice that the top three are sedation or analgesic reversal drugs. So we also need to think about, antidotes for drugs that patients might be exposed to in our hospitals as well. Again, as a reminder from this slide, we've talked about where we can access some of these antidotes if we don't have them in stock.
Highlighted in, in pink are the sort of more traditional antidotes that we, we think of. But there's plenty of other, medications on there that we use in these acute toxicities to relieve clinical signs and, and can almost be kind of thought of as, as in the same vein, not necessarily reversing the toxin, but as important for sort of treating them. So we can get hold of these things nice and early if we need them.
And so if we start with our, our first case of the evening, imagine that we've had a busy day in the hospital, maybe we've just finished our ops list, and we were just about to, we just stepped foot in the tea room to get our, a well-earned cup of tea that day. And you get a page or a call and one of the team says, Can you come and look at Fluffy, patient in ward just not doing terribly well. And this is, whilst we normally think about intoxication, owners calling up the animal's gotten into something.
As we said, intoxication can happen in the hospital, often in terms of drug overdoses. And again, there's far too many of those to cover individually here, but I find a combination of VPIS and, and often a drug formulary. So plums is one of the ones I use quite commonly, is having a decent amount of detail in there.
But of course, there's, you know, whatever you have in your shelf. I find them quite a good starting point after I've initially assessed that patient, just so I can brief myself and I expected adverse effects or just how bad, a particular situation might be. But since we're specifically talking about antidotes today, and given that several of the antidotes listed in that table I showed a couple of slides ago, relate to analgesic and sedative drugs, I thought we'd spend, a couple of minutes at least talking about their application in toxicology.
So for this drug group in particular, as you said, it could, overdoses can occur inside the practise, but can occur outside too, and That may be something that we can, we can test for and we've talked about sort of sources available for testing for illicit drugs, so analgesics and sedatives and, and plenty of other classes as well. Times that we might have this situation come up and where we might end up thinking about, does a patient need an antidote for one of these drugs is probably the most common one is if there's a dosage calculation error, so that's towards the side of an accidental overdose, you know, switching out the mix the cake per per hour for per minute, all of that kind of stuff. .
Dosing errors a big sort of common cause of of intoxication. It might also be that we've got a patient who's had a perfectly standard normal dose, but just isn't handling it well for whatever reason, and, and that has become unstable and that's a patient that we want to administer a reversal agent to as well. Might be accidental patient exposure, so not that we necessarily, use these so much anymore, but a good example of this in previously would have been patients who'd maybe eaten a fentanyl patch or, even patients who'd had a fentanyl patch and then found themselves near a heat source that increased, systemic uptake from that patch.
So kind of accidental exposure, however, that form came about. And another example in the context of toxicology is maybe there's a, a patient who we've just induced emesis with some appomorphine, say, or one of the other sedative drugs if it's, if it's a cat. And then all of a sudden, between giving that emetic drug and the MS is occurring, the patients become clinical and we really want to get that drug out of the system as, as quickly as we possibly can.
That might be another indication as well. And with all of these reversal agents or antidotes that we're talking about, then we're typically choosing to give them intravenously if we possibly can in these situations just to get them on board as soon as possible. Talking about opioid overdose specifically as being a drug that's used in, in practises sort of almost all day every day if you like.
What kind of clinical signs would we see in a patient who'd had that? It kind of makes sense that you'd see depression of the cardiovascular, the respiratory, and the neurologic systems, since that's kind of what their, what their kind of known side effects are. So in an overdose situation, we just see more of those.
So, Typically cardiovascular depression with bradycardia hypertension associated hypothermia oftentimes. Respiratory depression in terms of, decreased respiratory rate, decreased chest excursion resulting in hyperventilation. And quite pronounced neurologic signs, whether that be changes to pupils or changes to the, the mental status along with some others.
So typically they're all, all depressive effects. And that's in the dog. Cats, of course, have to do their own thing.
And given that they have a sort of different metabolic pathway and maybe don't handle these drugs necessarily as well, we tend to see excitation as a sort of overdose and sign in, in cats as the old phrase about the morphine mania that we used to see in cats, it kind of sums up the situation quite well, in that species. So more depressive in the dog, not so much in the cat. How do we treat opioid overdose if we maybe just it's just happened, what do we do?
Well, if it's been a gastrointestinal exposure and if it's appropriate to do so, then we can certainly consider induction of emesis and activated charcoal admission as we talked about before. But here for me, the tricky thing is figuring out is whether that's an appropriate thing to do. So, how severe are the clinical signs?
Is this a dosing error from, you know, for example, I may be meant to give a 0.1 weeks gig of methadone, I've given a 0.3 or a 0.4.
Trying to think is, is that, yes, it's more than I wanted, but it's going to cause clinical signs I'm gonna need to address? How severely affected is the patient? Are they already clinical for sort of, neurologic depression, in which case induction of emesis is off the table, and therefore, it's not safe to kind of proceed with that course of action.
So, kind of just making a clinical judgement about is that still the right thing to do. If we want to, specifically target the opioid overdose, and this is where our antidote comes in, of which naloxone is the most commonly used, drug of choice. The dosing written up on the slide here, many routes by which it can be given.
And it's really, really good at, reducing respiratory depression in these patients. And Respiratory depression with any resultant hypoxia is the most common cause of death following overdose of, of an opioid substance. And so it's really, really tremendously convenient, in fact, that that's what this, this reversal agent will, will then overcome.
So I basically consider giving it in any patient with significant depression following, an unintentional overdose of, of opioids. As you said, they're not these, anti antidotes aren't the be and end also in these patients, we still need to consider oxygen therapy if, you know, the respiratory depression is severe. And subsequently, we might need to think about if I've reversed all of the methadone, for example, then what am I gonna do when the patient becomes painful later.
But I guess that's a, a sort of topic for, for a different talk today. But this is sort of the, the general overview of sort of opioid antidotes, really. Moving on and switching the topic onto the use of one of the other most commonly used antidotes and a common intoxication.
Again, the phone rings a client this time saying her dog just ate some rat poison. And specifically, this is the owner of Finley, who's a very innocent looking 6 month old mal neutered Labrador, presenting complaint. He's been exposed to an anticoagulant rodenticide 2 hours earlier.
The owner knows that this is the first time he could possibly have got access. Maybe the, the, you know, the product was just put down. But what isn't known is how much has been eaten, if any.
Finley has prior form, so he has a history of eating and subsequently vomiting up a sock a month ago. So it's entirely feasible that he's, eaten something else today, but otherwise pretty healthy, and his physical examination is, is perfectly normal. So we're kind of going to think about what we do with a dog like him in a bit more detail.
We've talked in previous webinars about just how critically important that sort of toxologic history is, especially for rodenticide type toxicities, to make sure that we do perform the appropriate decontamination, it's done safely and that we're giving the right antidote if if appropriate. Certainly for the anticoagulant rodenticide toxicities, they're the ones with the antidote, given they're the vitamin K antagonists. But even within that group, we do know that there's, a lot of variation in, in how these specific agents act and, and how much is taken to poison animals.
So, For example, with some types like brum, for example, it takes a really small amount to cause poisoning, especially in dogs. But some other types have seemed to have a much wider margin of safety, so things like the bromodiolone, for example, it takes quite a, a lot more to cause poisoning. So there's a bit of, there's certainly variation within that group and variation as to how long these, these toxins will, persist in our patients as well.
Of the anticoagulant rodenticide toxicity patients in, in general, how do they cause their toxicity? Well, I think most of us are probably familiar with the fact that they cause an inactivation of some pretty vital, clotting factors. So factors 279, and 10.
And they're highlighted with the, the purple circles on this slide, and we can see they're, they're pretty big players in coagulation. They're kind of covering both arms of our traditional clotting cascade. And so if they're inactive and because of this, toxic principle, then we're, we're gonna have a bleeding tendency, and these patients can actually can present, as we know, with, with spontaneous bleeding.
What exactly is happening to kind of make this bleeding tendency happen? Well, we said it was the clotting factors 279 and 10 that were affected and. To make them work normally, they, they normally exist in an inactive form, and they have to be activated in order to sort of provide clinical hemostasis.
And for that conversion from inactive to active, we need something special, this this substance in this box here, this hydroquinone. And what this kind of does, I, I think about this in fairly simple terms, is it basically sacrifices itself in this activation process to make these activated factors. And in doing so, it inactivates itself, if you like.
But that's OK because in health we've got this little enzyme and just down here, this vitamin K epoxide reductase, and that makes it all better and it converts it back to the active form and it can carry on and activating these clotting factors. And so in health, this system works perfectly. We've got activated factors available all the time.
In anticoagulantogenticide toxicity, the problem is that this is the, the critical point as shown by the, the highlighted bit here where these, toxins work. So they, they basically just stop that lovely working cycle and ultimately mean that we can't get activation of these clotting factors. And therein lies the big problem.
The good news about this whole situation is that this inhibition of this enzyme by these reddenticides is competitive and reversible. So by that we mean if we give enough vitamin K, we can actually reduce inhibition or completely annihilate any inhibition of it and allow continued activation of clotting factors. So we're basically overriding the toxin, which is quite handy.
And the other really nice thing about this system is that, there's a known delay in the onset of clinical signs, of, of bleeding after consumption, of, a rodenticide of this nature, because there is a certain amount of circulating activated factors already present. So there's going to be a little bit of a time lag between ingestion of the toxin and getting clinical signs of bleeding. And for me, that's a great thing because these, the bleeding that we tend to see with these, this particular toxicity, although delayed, so typically within 3 to 7 days of exposure, it's pretty bad and oftentimes in, in places that's really not that convenient.
So, It affects clotting factors, as we said, so it's expected that we can see some quite large and cavity bleeding as we tend to with any other kind of clotting factor deficiency. But it, it feels like that there's a, a, a lot of cases will have bleeding to do with the respiratory system. So, whether that be, a hemothorax, actually sort of lung bleeding, kind of fairly inconvenient places to bleed, but fairly commonplace.
But can basically bleed anywhere, anywhere at all to the point that we can get patients becoming anaemic and having clinical signs of, of hypovolemia as well. So when bleeding happens, it can be really, really severe and life-threatening. It's also pretty unpredictable where it happens.
So we know that there's various sites where, where bleeding might occur as listed on the previous slide. But, bleeding literally can occur anywhere with this kind of, toxicosis. And this was a, a case series of four small breed dogs, all them dogs who We breeds prone to tracheal collapse, and they presented with, tracheal collapse because of bleeding into the tracheal wall.
So actually sort of tracheal mucosal haemorrhage. And that caused, as you can see on the, the radiograph here, this is sort of the, the image taken when the patient was clinical for the bleeding and marked narrowing of the tracheal lumen, really quite impressively. Which did resolve with treatments and this is sort of the, the before and the after.
We can see that this is really markedly improved, with treatment, . Of the, the, of the patients, 3 out of 4 of them in this study had follow-up radiographs, and all of those 3 had improvement in, and how they, appeared. And they were all treated successfully with standard therapy as we're gonna talk about.
But this, for me, this was kind of an interesting thing. It's not something I've seen clinically myself, I'll confess. But it's a really good lesson for me to say that bleeding can literally occur anywhere.
So if you think about sort of how the bleeding happens and and what the resultant coagulation abnormalities are. If we kind of go back to our 4 vital plotting factors that are affected in this situation, we'll see that they're affecting both arms of the clotting cascade and so ultimately, we'll see abnormalities in both sides, so in our measurement of PTT if we're measuring that and and PT if we're measuring that. What's interesting is that the prolongation in the, the PT is, is something that occurs first.
And the reason that it happens in a particular order, and they both don't happen together, is that factor 7, is the one with the shortest half-life of all of the affected factors. And so the one that gets depleted first and therefore, the, the PT becomes exposed as being deficient, and that's when we tend to see a prolongation first. That will always happen first.
And we'll always be the most markedly abnormal of the two of them as well, which is a useful thing to know, we'll come back to. Ultimately, we'll get prolongation in the PTT as well, as these other clotting factors. So 29, and 10 become affected.
And also, if we have a patient who develops clinical bleeding, then we'll start to lose even more clotting factors, all of the others, from consumption from bleeding as well. So, ultimately, if, if left, we will see, a prolongation, in both sides of the clotting cascade. So what do we do if we're lucky enough to see the asymptomatic case?
So we've seen this dog who may or may not have eaten some anticoagulant rodenticide, and what do we do with them? Well, It makes sense if it's a recent exposure and again, there's no contraindication, sorry to do so. We'll routinely decontaminate them, induce emesis, give activated charcoal, .
It's a nice thing to do from a confirming suspicion of ingestion. If you induce emesis and it comes out blue, then pretty suspicious that that's probably what's happened. But equally, the absence of blue vomit, for example, doesn't rule out exposure either, but it may work in your favour to confirm a suspicion.
And we talked about this before in terms of agents that we'd use. For really, really large exposures, we might consider, do we want to do a lavage procedure, specifically for if a pet's got into, an excessively large amount. If we kind of know that, we might think about is that the best way to empty them out, but again, it's very patient specific.
And ultimately when the emesys or lavage is finished, then again activated charcoal to decrease uptake is appropriate. So that's what we've kind of covered so far, but what's of more interest for today is what about using an antidote? And really at this point, we've got two choices as to how we go about administering an antidote.
. The first option is to kind of It's a, a watch, wait and see type of approach. So it's to say we know we've got an antidote, but let's kind of actually see, do we, do we need to give in. And so the, the first approach is to actually say, we'll decontaminate the patient, check that that was the, the actual exposure time that we, we, we know has occurred.
Send them home and get the patient back 48 hours later for a just a PT test. And the rationale at this point is that if 48 hours later we have a completely normal PT, that means for sure that there hasn't been toxic exposure. We don't actually need the antidote at all.
And that window, that 48 hours is really important because it will be with, that's a really short window in which clinical bleeding hasn't occurred, but we do get that early prolongation in PT before we start to get a generalised coagulopathy. So the window of testing is really important. So as you said, if it's normal, we definitely don't need therapy, you're all done.
Thanks for coming. If the PT is prolonged, then actually conversely, we know that intoxication definitely has occurred and we definitely absolutely do need vitamin K antidotal therapy. And this same approach has been looked into to see if it's safe.
And, it was actually performed in the hospital I did my residency in, well, I guess there was a lot of pest control work out there. And, we saw a lot of these patients. And of all of the dogs looked at in this study that had this approach, it was very routine.
Only 9% of the possibly exposed cases needed vitamin K. So, that's a massive proportion of others that may otherwise have been treated with it anyway, didn't need it. And of those 9% who had that vitamin K therapy started 48 hours later, none of them bled, which for me is a really important thing to say that this is a safe thing to do.
I should say that this is, this is my preferred approach. This is how I manage the vast, vast majority of the patients I see for this. But it only works if we have a patient who's systemically well, and healthy.
So this is not going to work if this is a patient with significant liver dysfunction, that might have concurrent sort of clotting factor problem because it just isn't going to work as a screen then. And the other word of, of note or caution is, there are, there is a case report of, a beagle, who ingested anticoagulantar denticide, and this approach was followed. And, and, some beagles are not all, obviously, but some can have a hereditary factor 7 deficiency, which means their PT will always be prolonged, which obviously complicates things if we're trying to use a prolonged PT as, as a bit of a screen.
So, I think I'd be hesitant to use that in, in dogs, Of this breeder would certainly think to have to sort of think through what the results meant a little bit more detail. But in your average healthy patient, this is sort of a, has been shown to be a really nice way of managing things. The other option, may be a bit simpler, is to just give the vitamin K therapy anyway.
And now we have the tablet form, that's, easily available and in stock, etc. That's a valid option either which way. So we might consider doing this anyway if we don't know exactly when the patient might have been exposed since that window of timing we said was really important.
Or if I just can't get a PT run, within that time period and get the result back in a timely fashion, or if I have a client who I just don't think is gonna come back, then I, they, but I'm worried enough to think that they might need therapy, then those might be patients I prescribed that in any way. If we do prescribe vitamin K therapy in the asymptomatic case, then the dosage is sort of the same as on all of the the TV and marketing which is really nice to kind of laid out with, you know, dosing and and how to do that, etc. In terms of duration, if we know the exact, agent that was ingested, then we, we can get information from the sources we've talked about as to exactly how long we need to treat.
But if we don't know, we know it's an anticoagulant denticide, but don't know exactly what type. Then, generally speaking, I'll think about doing an initial 2 to 3 week course, and then sort of reassessing, towards the end of that. Has that been been long enough.
So, kind of a, a reasonable starting point that we, we can sort of obviously adapt as needed. And in terms of discontinuing therapy, knowing when to do that, again, a nice way of doing that is to say we'll treat for, you know, whether that be 2 weeks or 6 weeks or whatever our, clinical information is telling us to do. And then we'll discontinue the therapy and then 48 hours later recheck a PT and the nice thing about that is if it's normal, then all of the antire toxic toxicity is gone, so we can discontinue treatment safely and confidently.
If it remains prolonged, then we know that actually there's still some toxin present and so we'll need to restart treatment and we can go for another 7 to 14 days, again, whatever we think is appropriate, and sort of repeat the process. And again, this is quite a nice way of deciding what to do, assuming that the patient isn't having repeated exposures, which is obviously gonna make things a bit more complicated as well. If you've got a symptomatic patient, so a case comes in unwell several days after a possible ingestion of an anticoagulant rodenticide, then we could have a, a patient with bleeding from that, or we could have a patient bleeding, bleeding internally where we're thinking, could this be a rodenticide intoxication.
So in any kind of symptomatic patient, our priority is initial assessment and Verifying, any anaemia, looking for signs of acute bleeding. So this kind of very early warning sign of a normal PCV in a lower total solid suggests really acute bleeding prior to the onset of anaemia. And using patient care ultrasound for evidence of internal bleeding and all of the various sort of cavities and, and potential spaces that we've talked about so far.
Followed by, stabilisation, sort of one suggestion here for how we treat any, any hypovolemic shock. We then kind of move on to thinking about, well, should we do some coagulation testing to confirm the presence of a coagulopathy. And as we said, if we've got a patient who's symptomatic, who's bleeding, we're gonna see a prolongation of both the PT and the PTT, .
But even in these cases, the PT will still remain relatively more prolonged compared to the PTT. So if you work out sort of, you know, percentage prolongation, for example, the PT will always be more than the PTT. So for example, the PT might be out of range high, the PTT isn't, or if they're both readable, then the PT will be percentagely more prolonged.
And that's a really, really helpful, pattern because lots of other causes of, of bleeding due to, coagulopathy, whether that be hemophillias or liver failure, or DIC or any of those other fun stuff. It's the opposite way around. The PTT tends to be the more prolonged one.
So this is like a really good signature signature mark as well. And in these patients therapeutically, then again, they, well they need an antidote, they've clearly been exposed, they've got a problem. And this is where I'd use the injectable formulation, and use that until I can get them to a point that I can get them onto oral medication.
And this is great and it's something we absolutely need to do, but we do need to bear in mind that after giving the antidote, it still is gonna take anywhere depending where you read from 24 to 48 hours for those clotting factors to become repeated to the point where bleeding will stop. And so if we've got a patient with ongoing clinical bleeding who's unstable, then it's not, it's important, but it is sort of one of the combination of therapies that we'd use. And in that case, we think about whether or any clotting factor replacement from a plasma containing product is important.
And so if I've got a patient with life-threatening bleeding, maybe one bleeding into the, the lung or the plural space, for example, this would be a patient I'd think about doing that. And dosage wise, I feel like 20 mL per kilo definitely stops bleeding. 10 mL per kg might, 15 probably does.
So I, I tend to kind of aim for up to around 20 mL per kilo, depending on the patient size and the sort of unit size. And you can choose either frozen plasma, or fresh frozen plasma. Frozen plasma has your, your big kind of 4 clotting factors we've been talking about.
But if you've had subsequent bleeding and potentially consumed a bunch more factors, then fresh frozen plasma might be, a more thorough choice. If they become anaemic, then we might need to consider giving them something containing red blood cells, whether that be packed red blood cells that we can access relatively easily or freshhold blood from a sort of in-house donor. Or alternatively, these are great cases for auto transfusion, given this isn't contaminated blood, it's just, coagulopathy blood.
And so we can simply collect that, into a stringe and give it via a philtre, not really needing to anticoagulate it because hopefully the blood will have been, have sort of lost its fibrinogen content, so we shouldn't really be worried about administering clots. So, That's kind of a nice alternative to administer but by itself, the auto transfusion is just delivering back pack red blood cells, we'd still need some kind of product to give the plasma-based component to. And for the kind of more challenging cases, just kind of before we move on to the, the next topic, these are, these are subjects I found quite challenging.
So if they're actually bleeding into the lung itself, then obviously oxygen, keeping them on the drier side of life, so avoiding kind of fluid, excessive fluid therapy. And if they have any, anywhere else bleeding within the chest, kind of managing that more to try and improve oxygenation. For a hemothorax, then thoracocentesis can be done.
Obviously, we'll use our smallest, needle possible and really good technique to try and, decrease any bleeding tendency. Removing only enough just to relieve respiratory distress, so any left, any blood left behind is, available for reabsorption to sort of create new red blood cells again. And obviously, in combination with the vitamin K and plasma that we talked about.
And then pericardial haemorrhage, is, is the kind of the riskiest one of all. Like if they've got cardiac tampona, then they need pericardiocentesis along with the concurrent therapies we talked about. And it's a case of kind of, in my mind, getting the vitamin K on board as soon as getting the plasma going in and then, getting on with the pericardiocentesis and hoping that I've got enough plotting factors in there to not cause a, a bigger problem than I started with.
So just to finish up the prognosis, asymptomatic patients with this approach, excellent, assuming that we know the time of exposure. For the symptomatic ones can do really, really well, but, some sites being a little bit trickier than others. So this is quite the, quite the day in our clinic.
The phone goes again, somebody's calling to say their dog just ate some horse when we're on the yard and and what should they do about that. So the particular patient we can have in mind for this case example is, is a 4 year old female spade border collie called Fly. And she's presenting neurologically abnormal with a history of when we calculate it as ingested about 6 migs per gig of of an equine ivermectin and worming paste about 8 hours previously.
On initial assessment, and she is very stable in terms of her cardiovascular and respiratory systems, but neurologically, we've got some marked abnormalities as we can see here. And this is classic ivermectin toxicity signs. When this drug is present in high enough concentrations to cross the blood brain barrier, then we see neurologic signs as kind of the, the major malfunction.
And some of those are listed here. They can be really quite a variable in severity, but can be really markedly severe to the point that they're, they're life-threatening, life-ending for some of these patients. And so this is a pretty high stakes case.
This is 8 hours later, and this is a symptomatic dog. So I think we can all agree that it's really too late for induction of emesis. And so we're thinking about how we're gonna manage this patient.
We've got supportive care, but given a lot of these dogs can have really severe respiratory signs and including respiratory failure and may need to have sort of assistance with their breathing. That, that may be a patient that we can't manage for practical purposes, financial purposes, and these patients can have a really prolonged recovery in the hospital with ongoing neurologic signs, absence of gag reflex, predisposed to aspiration pneumonia. They can, they can have some, some really, really tricky recoveries.
Do some dogs have it worse than others? Well, I thought this was a, a good point to mention, a little bit of an aside to say, yes, some, some dogs can. And what I normally in, in mammals to have a toxicity of this drug, in mammals, you need, a much higher dose than you would if you were trying to poison a worm.
The exception to that is if you have a mutation in a specific protein, the peak glycoprotein, which is, a transmembrane protein is shown here that should normally limit ivermectin or some other drug penetration into the central nervous system and aid its excretion. So there's this little kind of safety protein there that normally should kind of protect our own system against this. This proteins encoded by a specific gene and we do know that there are some dogs, if they're homozygous for a specific mutation, then this protein just doesn't work and so drugs can freely access the central nervous system and therefore have more of a toxic effect.
And there's lots of, lots of dogs, affected by this, we tend to think about, Being these kind of like collie type dogs that are affected, but many cross breeds will have come from affected lines, so it's possible to see it in any breed as well. And there is a genetic test, available. So it might well explain why a patient might look particularly bad for a given dose.
And certainly, any drug that we do know is sort of handled by these pig lyer proteins in one of these, potentially susceptible breeds, we do need to be a little bit careful. And drugs known to cause a problem in this regard are things like the ivermectins, celemectins, etc. But also things like Aceromazine, butrophenol, some chemotherapy drugs as well.
So it's worth just kind of thinking about some dogs are gonna handle things a little bit differently. He said one of the most exciting developments in veterinary toxicology in recent times has been the application of this, these intravenous lipid emulsions as a sort of decontamination or antidotal strategy. And I'd almost use it as a sort of describe it as an antidote for sort of lipophilic drug toxication.
What actually is it? It's this stuff that comes in this kind of white liquid that comes in, in a bag. And what's actually in there?
Well, they're basically fat droplets that are similar to our sort of normal endogenous colour microns that would come from sort of normal fat absorption, in the, the GI tract. And they come in, they're kind of used to what the, the body is used to. And they're cleared by the various mechanisms that we, we have listed here with these breakdown products of glycerol and free fatty acids which can actually be used by the, the body tissues as an energy source.
So that's kind of what's what's in, in this bag. And the principle is that we can give this this solution intravenously and it works as an antidote almost certainly works to improve clinical signs by one or more of, of several potential mechanisms. So, Depending on the exact toxin, there may be one that predominates over another.
In practical terms, it might not really matter as long as the patient gets better. But for interest's sake, there's a few current theories about how they work, the predominant one being a sort of lipid sync sequestration effect that we'll talk about. But there's other ones listed to things about, various metabolic effects or kind of how the distribution of the, the toxin is affected and therefore might relieve the patient of clinical signs.
The lipid sync effect is kind of shown in this, this figure here. So, if you imagine that you have a a little toxin kind of circulating in your intravascular compartment. And you infuse this lipid syndrome into the intravascular space.
It's in the circulation. What it actually does quite nice is it binds up this toxin, inside these kind of little lipid, lipid spheres, these little lipid, compartments. And then the toxin's trapped.
And that's quite a nice thing because it means that then there's less of it free, that it's a free toxin that's the most dangerous part. There's less of it free and circulating and available to go to the tissues and kind of cause the, the negative clinical signs that they might otherwise do. And we said this, that we think this is the most important mechanism.
Once we've given these fat droplets and this mechanisms to clear that we talked about. And in some cases, some of these early kind of studies when this was used, there's some data to show that, as well as just binding any of these toxins in the circulating volume, this kind of lipid pull or lipid sync effect might be strong enough to actually pull some toxins out of tissues that they're already in causing trouble back into the circulation, where they can be eliminated. Which is quite a nice thing that, as well as dealing with toxin that's that's present, in the intravascular space, it can deal with stuff that's, that's already causing an issue.
There's some stuff to say that actually these lipid emulsions can directly improve cardiac performance and maybe it's because it's an energy source, and maybe some other reasons, but again, might be worth a consideration if we have a sort of cardiovascular dysfunction from a specific intoxication as well. When won't we use this stuff or really any lipid-soluble toxicity, then it's in my mind as to, is this a potential antidote. And specifically for, we'll talk about, different drugs, but for neurotoxins in general, since it's so good at kind of, that's a very lipid, dense tissue, obviously, and it, it, these things are so good at pulling these toxins out.
And in these cases, especially, we tend to see really rapid clinical improvement in these patients really turning their, their signs around very, very rapidly. But again, even though it's easy to get kind of caught up in the excitement of this antidote, we need to make sure that these patients are stable for therapy and it's, it's a supplementary therapy, rather than the sort of substitute for, a therapy, if you like. In terms of specific applications then here's a list of things where there's been all kind of reports or clinical experience directly and using these products.
So they'll see that, that they're all lipid-soluble drugs, that's kind of a, a prerequisite, . And in the acute system, in the acute setup, we're kind of used to being able to use these, but As we kind of learn more about them, there's potential that they might be able to help later on, and there's a, a report about lipid therapy being used to improve or to treat blindness. Following sort of, after a patient had gotten over some acute ivermectin ingestion, it was able to sort of treat, more longer-lasting clinical signs.
So it seems like there's, there's a, a lot that this therapy can, possibly do. How do we actually administer it? Well, the dosing recommendations that we, we have in veterinary medicine at the moment are really extrapolated from human dosing where this is also used for similar purposes, as well as the doses that are used for parental nutrition, in, in those sort of critical patients.
And so I'll typically start with a conservative dose is kind of listed here, so a sort of a bolus over 5 minutes followed by a CRI repeated kind of as dictated by clinical signs. But we do have the, the option for patients that aren't really responsive to this sort of more traditional dosing, . That we can kind of up the ante, and, and use this kind of second strategy instead, .
And I, I want to kind of stress again that these dosing recommendations, they have been extrapolated. We don't really have trials at the moment to say, or studies, evaluating the use in terms of, safety, assessment. So it's, something that we'd use with, with careful monitoring and deciding that this is sort of the, the right thing to do for that patient at that time.
And so when, when might we consider using it currently based on what we know, then, because of the fact that we're, we're using this, not necessarily blind per se, but without that sort of extra, extra safety knowledge that it would be nice to have, we generally reserve it for toxins with a high morbidity or those with a really known potential for mortality. So, for example, this yvermectin dog, we, we know that's a, a whacking dose. We know that this dog's already very clinical and it's gonna get worse before it gets better.
And especially we'll think about it if traditional therapies aren't really working or, or we're in a state where we can't really afford to manage these patients, we can't really provide the care that they need and it might be a life-ending intoxication for the patient, or we could try lipid therapy is often a sort of time that it, it comes in. What about adverse effects? We kind of do need to have a balanced approach to this rather than me just recommending this wildly and and us not necessarily considering the potential risks of that.
We do know that these patients become lipemic and, you know, in one of the dosing strategies, that was our therapeutic endpoint that we'd made the serum lipemic. And typically we, we know this to be quite short acting and, and we don't think that it has any significant consequences. To the patient per se, but we do know that, having a lipemic serum can affect lab testings.
That is something we need to bear in mind further down the line and perhaps if we're taking blood samples for analysis, maybe take sampling them before we've administered this might be a good idea. In terms of adverse effects, there's really very few reports of that in the literature. There was one recent one of a, of a cat who had a permethrin toxication, who received a therapeutic dose of lipid, which subsequently developed a cornea lipiddosis.
It did resolve fully within a week. So, an interesting, an interesting case report. We don't really know how widespread that is as a complication.
And in terms of recent data, the VPIS most recent report, it does specifically mention there were two canine deaths associated with the use of this therapy, one from an overdose and one where this patient recovered from the, toxin, but subsequently developed pancreatitis. So there are, are potential, adverse effects out there. There's a plethora of other possible ones as well, so, contamination of this product is a, is a particular concern because it's a very nutrient-rich product with, with such a sort of high lipid content.
But with appropriate handling, and for lipid therapy, lipid emulsions, for, toxication purposes, there seems to be much lower risk than if we're using these solutions for sort of, a nutrition sense. So, we need to be mindful of how we handle them, but, overall shouldn't be a significant concern. There can also be various other reactions to the emotion, in people specifically, there's reports of sort of fat overload syndrome, it's termed, where patients can get hemolysis, they can get aerous, they can become systemically significantly unwell, get fat embolism, all these other very unpleasant things, but typically seen with overdose or really Really rapid administrations and more rapid than we've talked about in our proposed doses where you just overwhelm the body's ability to be able to deal with them.
And also, there are reports of pulmonary changes, so like an odd-like syndrome or the acute respiratory distress syndrome that we see in our sort of really septic, systemically and well patients, for example. Where in people there are reports of this and actually in, in rabbit models, they've used infusions of lipids to induce an acute lung injury, so sort of less severe acute respiratory distress syndrome. And so for me, it's, it's a, it's an interesting thing.
I'm not sure it's been reported in sort of clinical patients, but it does mean that if I have a patient with lung, pre-existing lung disease, I really need to think about whether or not this is the, the right thing to do or not. So, some kind of tips as to how, how and when we might use this therapy. And I think our knowledge of potential adverse effects and, and therefore helping guide our clinical judgement as to whether or not to use it is, is on its way.
The shift is going really well, somebody else calls up now and their dog's eating a packet of paracetamol and and they're calling on the off chance just should they be worried. And I think probably the short answer to this is kind of spoiler alert, the answer is yes, and we'll kind of talk a bit more about this specific toxicity being one of the most common ones that BTIS receives advice calls about, and talk about how the antidote kind of fits in there as a kind of last topic for this evening. So we know that paracetamol is an analgesic drug and it's an antipyretic drug used really commonly in human medicine, and sometimes used therapeutically in dogs that kind of the dose listed on this slide.
We know that we never administer in cats because of their susceptibility to it. And we do know that we do see excessive exposures and Typically in dogs it's accidentally accidental ingestion, so you know they, they've eaten the packet, they've kind of chewed it up. Whereas in cats, sadly, the, the more common exposure is sort of nice guided if you like therapeutic administration so the owners realise a well and it's given them the paracetamol like they would sell themselves to see if that helps and.
Really sorry to disrupt Lindsay, your microphone's just gone slightly blurry. OK. Is that any better?
Can you hear me a bit better now? Much better, thank you very much. Sorry to disrupt you.
No worries, I can hear you very faintly, so just just shout if there's there's another problem, and I'll I'll try in here. Lovely, thank you. No worries.
So yeah, so in terms of of doses of paracetamol that are toxic. Then in in dogs we're talking up to sort of 1 to 200 milligrammes per kilo, causing clinical signs, but cats really very sensitive, so clinical signs are seen as as low as sort of 50 to 100 mg per cake, but oftentimes as low as just 10 mg per cake, which if you think the average paracetamol tablet size is 500 mg per cake, means that really any exposure in a cat is, is a potential is a potential massive problem in fact. And so really the short answer should the owner be concerned, is yes and really treatment should probably be given for any exposure because it's likely to be at all or or in excess of a toxic dose.
Just a very, very brief refresher as to how paracetamol is normally metabolised. I promise we won't dwell on this bit for for too long, but it becomes relevant when we talk about antidote therapy. I if we kind of start with paracetamol up here, the way it's normally metabolised is it can, it's kind of metabolised in the liver and it can either undergo this gluconidation or a sulfation reaction, and that makes it into these non-toxic sort of byproducts that then get excreted.
So that's kind of quite a nice way to get rid of paracetamol. Alternatively, it can be metabolised by our good old friend cytochrome P450 and then it makes this little chat down here which I kind of I, I can never remember what this stands for, so I just refer to it as NaAqui and probably encourage you to do the same. And this has the potential to cause some harm, but in, in in normal state, it undergoes conjugation with something called glutathione that we'll talk about again.
And again, that's a non-toxic, non-harmful product. And so the paracetamol's gone, and, and the, the patient has been sort of saved from any toxic effects. If you have too much paracetamol and therefore more metabolism, then what happens is that these glucuronidation and sulfation pathways just get saturated and overwhelmed and therefore it's just not possible to have for all of the drug to be processed in that way.
And so it makes sense. What does it do? It goes via this cytochrome P450, makes this little napqui friend down here, but we kind of run out of the glutathione to be able to conjugate that safely.
And so we just send it with a buildup of, of this particular substance and then we end up getting these toxic reactions and we get this cell injury going on. So. Herein lies the problem that it's just by virtue of its excess, the body can't handle its normal metabolism and we get a build up of this sort of toxic products.
What does paracetamol toxicity ultimately cause? Well, it causes, in, in very simple terms, and potential liver failure, and also injury to red blood cells. So dogs tend to have more of the liver failure type signs, and cats tend to have more of the, the red cell signs, but obviously they, they do tend to have a bit of both.
And of the red blood cell signs, then they get a dishemoglob anaemia, they get formation of haemoglobin that we'll briefly talk about, but they do also get oxidative injury to the cells in general, so Heinz bodies is kind of shown here on the, the sort of smear pictures, resulting in a hemolytic anaemia as well, so they actually get a sort of a decreased functional red cell mass at the same time. Darcy said that the hepatotoxicity was a prominent feature with your typical liver signs predominating usually within the 1st 24 hours of exposure, with the usual suspects of the vomiting, anorexia, painful abdomen, jaundice, and elevations in sort of your liver parameters, etc. And that can be hepatotoxicity, but it can progress to just massive hepatic failure and and necrosis as well, so quite a sort of scale of, of injury it's seen as well.
We can see injuries to the red blood cells with methemoglobin formation and we can also see pallor from hemolytic anemias, and edoema formation, neurologic signs either because of severe hepatic dysfunction, hepatic encephalopathy or because of the issues regarding the, the, red blood cells as well. As you said, the signs of hemoglobinemia are the, the bigger ones in, in cats, and so we tend to see things like cyanosis, like dark mucous membranes, like dyspnea, edoema of the front paws and of the face, but we can also see, icterus, and all of the sort of liver enzymes being elevated typically sort of 2 to 3 days later in in these cats as well. So quite a sort of systemically unwell patients in both, both dogs and cats.
We've mentioned that haemoglobin a few times so far, but just to sort of refresh on what it actually is, . We basically at formation of this substance when you get oxidation or oxidative injury to the the oxidative injury to haemoglobin, sorry, in which the irons change from sort of FE2 plus or like the, the ferris form in the normal haemoglobin to the FE3+ or the sort of ferric state that you get in the haemoglobin. And the problem with that is it turns the the haemoglobin into something that just can't carry oxygen terribly well anymore.
It just can't really bind it, can't carry it, so it's kind of not able to fulfil it's it's destiny. And so you might think about methemoglobin being present if we get sort of characteristic colour changes to mucous membranes, it sort of brown discoloration being the main one, but sometimes quite dark or blue membranes we might see in other patients. Some, the blood can actually appear, this kind of same chocolate brown colour, or we might think about it if we've got a cyanosis that just isn't responding at all to oxygen therapy, and normally that should do something at least.
We might think about it then. So they're all basically related to, the signs of decreased oxygen carrying capacity of the blood. We might think about whether or not that haemoglobin or something similar could be present.
In terms of confirming this, if you know, if you have a patient with, you know, that we're suspecting has paracetamol toxicity but don't know for sure, how could we sort of confirm that that haemoglobin anaemia is present? Well, You can directly measure it and get a nice percentage, but you need current symmetry to do that which isn't that widely available and oftentimes you can't really sort of wait that long to kind of get this stuff back to kind of you need to know what you're dealing with a little bit sooner. But the nice thing about this is it's a really practical way of telling this and it's basically as simple as if you get a, a drop of patient blood and then put a drop on on philtre paper or similar.
It'll stain it a really brown colour as we can see in this test tube on the on the far left here. And these these three tubes here all have varying amounts of haemoglobin in them, so we can see really quite dark brown, a little lighter, a little lighter still, but really very different to the blood from this tube on the far right here, really red, markedly different. So we can actually sort of just look at the colour itself and sort of make a judgement of that.
Another way of doing it is to, if you have blood that you suspect has methemoglobin present, you can bubble oxygen through that blood, and it still won't turn red. So you can basically supersaturate it with oxygen and because this methemoglobin just can't, just won't bind oxygen, it doesn't change colour at all. And again, that's kind of a nice practical way of sort of telling whether or not that's likely to be present.
If our initial approach to treating these patients, then they're a massive concern. So the prognosis following any paracetamol intoxication has to be classed as guarded just because of how severe the toxicity can be. And it kind of makes sense that if you've got a patient with a more severe hepatic injury or more severe and red cell abnormalities, then the prognosis gets worse with time.
So there is a sort of dose effect to this as well. It's a really, in terms of that initial treatment, if we get this patient in very early on, we've really got a good chance to kind of try and stop things getting worse. But it's very, very time sensitive and we know for sure that the time from ingestion of this stuff to treatment is probably the most important factor in how we, determine their morbidity and ultimate survival.
And paracetamol is is really rapidly and pretty much almost completely absorbed from the GI tract. We're really good at taking it up, which is good from an analgesic standpoint, not so good from a toxicity standpoint. And we tend to see peak plasma levels potentially as early as 10 minutes, but maybe up to 60 minutes, or maybe sort of up to a couple of hours later for any sort of extended release type formulation, so.
It really is a case of once we've checked these patients are stable, no contraindication inducing MSS as soon as we can just to try and decrease the amount of absorption, following it up with activated charcoal for sure, again, just to try and minimise the amount of toxin that's getting into the system. And then up steps the the antidote. So this paracetamol intoxication is a really nice one that has a specific antidote that can make a world of difference to these patients and.
The antidote is termed Anatylcystine, I think Parvalex is currently one of the kind of trade names of the the formulation out there, but there's, other, other ones available as well. And this does a really nice job of reducing the extent of liver liver injury or the extent of haemoglobin formation or other red cell abnormalities after ingestion of of paracetamol. And basically what it does in a nutshell is it's a precursor to the glutathion molecule that we talked about.
So that was the thing that was neutralising this quite, quite dangerous kind of Naqui metabolite that we talked about. And it does a whole bunch of things here as kind of listed to, to basically try and lessen the amount of that Naqui and and basically kind of protect all of the, the cells as well. So it's really well placed to kind of undo the damage that the paracetamol is, is, is doing.
In terms of the dosing of it, we tend to give it as an initial dose of 140 makes the cake and given intravenously, and that the recommendation is typically to dilute that to a 5% solution. It typically comes with a 20% solution for injection, and then give that over 15 to 20 minutes. And then follow that up every 6 hours with a lower dose for at least 7 treatments, so that's giving us quite a sort of time period to hopefully outlast that toxic effect of the paracetamol.
But if we have massive overdoses, then we might need, to kind of carry that treatment on for longer. So if you've got signs of kind of ongoing liver damage and a red blood cell injury occurring, then it might need more, and there are some reports of patients leading up to sort of 17, additional treatments. So, again, it's sort of patient specific, but for me, most patients will do quite well with a sort of strategy as as listed above.
The injectable form is fine. We give that IV, not a problem. Oral administration of the NStylcysteine isn't recommended.
It's, it's really not well tolerated. If you've ever tried to give this stuff to a patient and you've smelt it for one, and it's really not nice, really not well tolerated, and therefore uptake probably isn't that great by the time they sort of spat all of it back out again. But the other issue is that it's also likely absorbed by the activated charcoal we've given, so it's really not being an effective antidote because we're probably not getting any systemic absorption of it.
So for me, oral administration is sort of the my least preferred mechanism of treating these patients. If you have, as I said, there are means to get the injectable products of this, but time is of the essence, . If you don't have the injectable formulation, but you do happen to have the inhalation, inhalational solution, there is a 20% inhalation solution as well.
You can give that intravenously in these patients, but the recommendation is that you use one of the little inline philtres that you might otherwise use for giving something like Manitol or, or feline blood cells, for example, but that's something that that is perfectly legitimate and reasonable to do. The IV formulation is tolerated, really well. I think we're, we're kind of used to using it in these paracetamol patients, but as a sort of trivia fact of the day for you, another kind of, benefit of anastocysteine is you can give it to patients with really severe pneumonia as a complete aside of toxicology, it's quite a tangent and taken us on.
But you can give it to patients that, you know, the hospitalised really really severely affected patients with pneumonia on oxygen, receiving IV antibiotics as a mucolytic and usually at the dose of 70. Makes the IV Q6 and we get this IV routinely and it's really well tolerated. So from a toxicology standpoint, back to what we're meant to be talking about, it's something that we, we don't tend to see any adverse effects from.
So generally, generally well tolerated intravenously, not so much orally as we've said. An additional treatment of paracetamol toxicity is really supportive care depending on their kind of organ function and and where the sort of toxins hit them worse so. Any kind of respiratory distress then obviously oxygen supplementation but may or may not help if depending on what's happening with the the haemoglobin situation.
In those cats where there's been really quite severe hemolysis, the Hein's body anemias, for example, then they might actually become anaemic to the point they need, a blood product. So they might need to sort of consider that. Supportive care in terms of fluid therapy, electrolyte correction, thinking about, sort of general supportive care for these patients.
In the literature, it's always written a lot about simestidine treatment and ascorbic acid treatment, so vitamin C and methylene blue. So the smetidine treatment is, it's an inhibitor of the cytochrome P450 system that we talked about. So it has potential benefits of reducing the formation of that toxic metabolite Naqui but In practical terms, it takes several days to become effective, and we can't use it in cats, so for me it's with availability issues, it's not necessarily something that would be a first choice per se.
I say vitamin C, it can be used to convert methemoglobin back to haemoglobin, but it's got really questionable, effectiveness and it may cause some gastric irritation. So again, it's not something that I'd reach for as a first line, and, I've never worked in a place that has methylene blue available, so we might be limited as to what we actually have in stock with these things and to be able to use them. So for me, they're not necessarily a, a first line treatment per se.
But other supportive care, just to finish up, if there's any kind of hepatopathy, thinking about if they're coagulopathic, thinking about do they need any other supportive care, GI medications, and certainly, for any hepatic injury giving Sammy or Denisil has really shown a positive effect for the treatment of this toxicosis. So that is all the things on this list, that is something that I, I definitely would consider along with the antidote and the other things that we've talked about as well. That's kind of a a whistle stop tour of kind of some of the most common intoxications where we might consider an antidote and how we'd use them.
But, thinking ahead to to next weeks it's the final webinar in this series, and it's the title I've given that is a, is a potpourri of, of, of toxicology and. I thought what would be nice is this can be a nice interactive thing is to actually have a little poll right now to kind of see for those of you attending live this evening, what toxicities you'd you'd like to see sort of covered next week. So we've got 10 options.
We've got ethylene glycol, chocolate, lilies, grapes, raisins, etc. And permethrins. Mushrooms, metaldehydes, and other neurotoxins, so there's the kind of tremogenic microtoxins, etc.
Nonsteroidals, xylitol, and marijuana. So if there's any kind of overwhelming wish, but for some of these, I can make sure that they're covered. So if we open up the poll now, hopefully you can, pick, pick whichever options you like, and then we'll see, see what we're gonna talk about next week.
OK guys, this is your chance to choose what Lindsey can talk about next week, so please get involved, please vote, and we'll just wait a couple of minutes for you all to have your say and then I'll share the results with both you and Lindsey. OK, we've got a fair few coming through already. That's good to know.
These are coming through pretty quickly actually, I've got 75% already. Oh, that's brilliant. Another couple of minutes and then we'll, I'll share the results with you.
OK, 76%, that looks like everybody's voted who's here. So I'll share the results. OK.
Well, the good news is it looks like there's, there's not too many unpopular options at least, so it seems like if I'd have guessed randomly I probably would have done all right, but, that's actually really, really helpful. So what I can do this week is I'll get, get this data and then we'll make sure that we cover the kind of the top, the top ones for sure next week. So again, that relates to if there's any other questions that might have been triggered from tonight's webinar if they relate to kind of one of these forerunners, the.
The grapes, the metaldehydes, the, the non-steroidals for sure, then we can definitely discuss those in in more detail next week as well, but thank you, that's really helpful for me. And I think that's all I have presentation wise tonight. So if anybody if they have any questions, can I come in I'm happy to answer those.
Excellent, and we do have a couple of questions already. While waiting for some more to come through, I'd just like to remind everybody that next week is our 4th and final webinar for this toxicology series, and it is on the Tuesday evening rather than the Monday, which is a bank holiday. OK, so for the first question, in cases of bleeding into body cavities, how do we get the erythrocytes back into the vessel?
Is it through reabsorption? Yeah, great question. So, yeah, let's say you had a patient with a heabdomen because of rodenticide toxicity.
If you basically leave it in there, then it will just be kind of broken down to kind of the constituent parts, but then they'll be recycled internally and kind of reassembled back into red blood cells again. So it's kind of, it's not really an auto transfusion per se, but it's sort of like a, a recycling of those bits. So it is by reabsorption.
It it definitely has its use because you're, you know, you're not depleting that that patient of those really quite important things that it could use, but. It isn't as rapid a clinical effect as, say, administering a transfusion or actually taking that blood out of the body into a syringe and then delivering it straight back into the intravascular space again. So there's probably a couple of couple of days delay if you just kind of leave it sitting within the peritoneal cavity.
And as such, if you've got a patient who's already clinical for anaemia, then that's probably just not a speedy enough way to go. So. It's a case of leaving it be and rather than sort of taking it out and throwing it in the clinical waste, and leaving it be for the body to do something with through reabsorption, but as a sort of more of a long term strategy as opposed to kind of treating acute anaemia if that makes sense.
Right, thank you very much. And one from Danielle, does Q6 mean every 6 hours for the acetylcysteine administration? It does indeed, sorry for my abbreviation, yes, that does mean, yeah, every, every 6 hours an acetylcysteine.
So after that initial dose of the 1140 mg per cake, then 6 hours later I'd go with the 170 mg per cake and then every 6 hours thereafter until I'd kind of reached my, my 7 doses or longer if I needed to. So yeah, thanks for clarifying. Lovely.
And we have one in the comments box. When do you stop Parvex? Liver enzymes are likely to be high, so how do you decide?
That is a great question. I think, to be honest, unless I've had some kind of crazy, crazy high dose, then I'm, I'm thinking I'm, I'm probably gonna say how's the patient doing after those that kind of couple of days of dosing basically. And if it looks like things have gotten as bad as they're going to get, so the patient has stopped deteriorating clinically and hopefully they're starting to improve at that point, then I'd say that's probably the right time to go.
And I think it is just based on clinical assessment. I, I guess if you're being academic about it, you could kind of measure levels of paracetamol and all this stuff, but getting access to that just, I mean, it's just not really, not really an option, or, or the sort of indicated thing to do. So I think it is just based on kind of clinical assessment.
Is the patient getting better? Have you treated over that kind of initial time period, things are getting better, I'd probably discontinue, at that point. If the patient was still.
Not rallying, I was worried this was a was a massive exposure and I'd probably continue it until the patients started to turn the corner, so it's a bit of an open-ended, bit of an open ended one to be honest. Excellent. And the next one, what is the mechanism of edoema in paracetamol intoxication when the albumin is typically normal?
No, that is an absolutely fantastic question. I've never thought of, and I have to say I don't know. Probably not what you wanted to hear.
But that is the, the honest answer. I'm gonna look that up and we'll cover that next week, so thank you very much for that. Lovely, thank you very much.
And a couple more is giving methionine after the event any value. In paracetamol toxicity and just a comment to say it's a brilliant series that you've done. Thank you very much.
Oh, thanks for the comment. That's good to know. Methiaine, I have to say I've never used it myself because I've always been lucky enough to be able to get access to the Nastylcysteine.
It is written about as, as a sort of thing that you can give as as an adjunctive thing, but I have to say I don't have the clinical experience to say whether that just by itself is enough to kind of relieve all of the the sort of toxic principles. So. I think it's, it's something that from where I've read about it, it's been in the context of if you can't get hold of nastylcysteine, then you might consider using that, but as I said by itself, I'm not necessarily sure how effective it it is and and I guess there's.
There's a lot of kind of variation in severity of intoxication, so maybe kind of like a lower rate one, maybe that would be OK, but I honestly I don't know about sort of potential higher exposures, but certainly would be indicated if you couldn't get access to an SR cysteine or there was delayed, then absolutely it's something that's perfectly valid to give. Lovely. And can ivermectin in GSDs cause grand mal seizures?
I think it can in in any, any breed to be honest, in terms of . The sort of the toxic principle and any kind of neurologic, any neurologic signs at all. So whether that be a sort of change mentation or blindness or, or, or seizure activity and so yeah, but I think the, the, some of the worst Ivermectin or that group of drugs to system seen have presented following a sort of history of neurologic decline, but I've actually presented with seizure activity.
So yeah, for sure, I think that would be within the realms of what ivermectin could do. Lovely. I'm not sure how to pronounce this drug name, but is paracetamol the same as Tylenol in the USA?
It is indeed, so it's exactly the same as as acetaminophen in the USA. So, I think the trade name for that is, is Tylenol. OK.
Lovely. And that seems to be the end of the questions. I'd just like to say a massive thank you to you, Lindsay, for spending your time sharing all of this talk with us tonight.
It's been great. No wor it's good. I'm glad you liked it.
Yeah, it's been excellent, thank you. And massive thank you to our sponsors, TM for sponsoring tonight's webinar and the rest of the series. And thank you to our listeners also for logging in and spending your time, listening to Lindsay's excellent talk tonight.
You will have a feedback form pop up in your browser, so please just take a few moments to fill that in, and then we can send any feedback to Lindsay, and I look forward to hearing next week's final talk, all tailored around the decision that you guys have made on the poll question.
