Welcome to this evening's webinar on toxins. How I'm going to approach it this evening is the first half is going to be on how to approach different types of toxins. So global approaches toxicities in general.

While the second half, we're going to talk about more specific toxins. As there's so many different toxins that we could potentially talk about, what I'm going to bring to this evening's webinar is more on what's been more recently. Reported and cited in the recent literature.

So something that you can get a little bit more out more out of further than your textbooks. So first of all, looking at the common toxins reported and looking at what species is more commonly reported is the canine, so dogs. So you can see in the paragraph on the left-hand side, the, the grey, figure showing canine intoxication and feline only is a red one, which is only less than 25% being reported.

So the most common species is canine, followed by feline, then rabbits, and then other various things. The table on the right-hand side is the more commonly reported toxins to the Veterinary Poisons Information Service or VPIS. And this is a combination of dogs and cats and other species reported here in 2017, which is the most, is the most recent report on the website currently.

So they include non-steroidals, anticoagulant rodenticides, chocolate, paracetamol, grapes and raisins, etc. Unknown toxins, Xylitol, fertilisers, vitamin D, lilies, pyrethrins, and metaldehyde. So we'll talk about some of these, but not all of these.

So first of all, before we talk about any specific toxins, we need to think about the toxicokinetics. And this approach is really important, particularly if you come across a toxin which you've never heard about, you might have to do a little bit of a Google, and, it may not really be specifically reported on how to necessarily treat each particular toxin that you may come across. So, first of all, when I'm thinking about toxicokinetics, it's same as pharmacokinetics, we're thinking about things like the LD 50, so the lethal dose in 50% of animals.

So this means that approximately 50% of animals died with this particular reported dose, but it's not actually the toxic dose, so we just need to keep that in mind. Also, we're talking about only 50% of the animals. So some animals may not die with this dose, but some animals may die with even lower doses.

The next thing is the mechanism of action, and mechanism of action or different toxins or even different drugs, drugs will tell us the potential adverse effects. And when we're thinking about toxins, when we're different toxicins can actually be different drugs, drugs that we use, so kind of rogenic. Issues as well as drugs that humans may use as well.

So, actually looking at, you know, plums or the BSAVA formula can be really, really helpful when we're looking at different toxins. Next one is it, is it acidic or alkalotic. So very acidic and alkaline substances can be causeic to the mucosal surface.

So, things like emises is contraindicated. Next one is, how is it absorbed? We normally think about things being absorbed through the gastrointestinal tract, but areas like the bladder, so things like chocolate and caffeine intoxication can be absorbed by the bladder.

So actually having a permanent fully urinary catheter can be useful in minimising further absorptions and toxic effects. And don't forget about things like ocular and dermal toxins. It's also really important to think about how quickly these different toxins are absorbed.

If they're absorbed very, very rapidly, then the decontamination using emesis may not be as effective. Next question to ask yourself is how is the toxin metabolised? Most of the time it's metabolised by the liver, some toxins can be metabolised by the lung.

And also the actual toxin ingestion may not be so toxic, but the metabolites may be more toxic. So thinking about how does that specific toxin get metabolised and into what substance is really important and doing a little bit of research on that. So is there enterohepatic metabolism?

Mean, does it get reabsorbed, metabolised, and circulated through the liver and excreted through the bile. If it has enterohepatic metabolism, the, the toxin could continuously get excreted into the guts through the biliary system. And the rate of enterpatic metabolism can vary depending on the different toxins, and we'll talk about some of the very slowly metabolising or drugs we're having very slow antibiotic metabolism today.

So does it bind to charcoal? We'll talk about different toxins which don't bind to charcoal later on this evening. And finally, how is it excreted?

Most of the time we think about toxins being excreted by the kidneys and thinking about if it is, is it in its inactive form or active form. Other areas that they can get excreted is through the faeces and also bile. One of the things which is a little bit in fat at the moment is intralipid therapy.

They're thinking about is it lipid soluble, and we know this by looking at the log peer of the substance, and we'll talk further about intralipid use today. And finally, are there any antidotes? And I put a crash cart here because I think it's really important to have different antidotes in our crash cart.

I have a bag of intralipid in my crash cart as well. And we'll talk about other different types of antidotes available for different toxins. And when is the peak absorption?

So that's really important to know, in regards to when should we see the clinical signs. So if the peak absorption is in, in 2 hours, and the animal ingested it 1 hour, ago, then it's important to really monitor those patients. If the peak hour is 2 hours and the dog presents 12 hours later, then you will be fairly certain that And the dog's not showing clinical signs, that is, then you'll be fairly certain that that dog hasn't ingested the, toxic amounts.

Other things to finally look at is the half flight, so how long should the clinical signs last and also considering how long to treat that particular patient. But before we go on further, I think I need to remind everyone is that when we're thinking about intoxication, we think about, you know, how we're going to decontaminate, how we're going to treat that particular toxins. But before we do that, we need to remember, we need to treat the patient first.

So stabilising the cardiovascular, respiratory, and the neurological system. I won't go further into this, but I have previously done a a a lecture on a webinar on on triaging patients. So we'll go on to decontamination on how we can get rid of these toxins.

One of the first mechanisms that we can use is emesis. So emesis is indicated if the toxin was ingested within. The last 2 to 6 hours.

This time frame will vary depending on which textbooks you read. And so it really depends on how quickly the the toxin is absorbed, and also the gastrointestinal transit time in that particular patient. Sometimes when a toxin is ingested, it can have a gastrointestinal effect and can delay gastrointestinal transit time.

I've put here just a couple of pills here. So if you think about, if a dog or cat has eaten a very small pill, even if it's in its, toxic dose, most of the time these pills might get absorbed, within the first half an hour or maximum 1 hour, and they're just a very small tablet. So often in these particular cases, a meass may not be so effective.

Most of the time we can use apomorphine, we're talking more particularly in dogs. And the complication of Osis includes aspiration pneumonia. And contradic indications that any recumbent, unconscious, seizuring patient, or if there's no gag.

Really, if I think a patient is looking neurological, and I can't be certain that they have a good gag, in those cases emesis is contraindicated. If there's a caustic substance, which is alkali, acidic, or bleach. And any petroleums and also detergents are contraindicated.

These are a couple of really important reports in 2017 looking at the use of hydrogen peroxide as an emetic agent. Hydrogen peroxide, I guess, is more popular in the use in the United States, but also has been used in the UK as well to induce the emises and more so in cats because epomorphine is not so effective in cats. This first case report said no sorry, necroulcerative hemorrhagic gastritis in a cat secondary administration of 3% hydrogen peroxide as an emetic agent.

So in this particular case report, the cat had thought to had eaten a foreign body, and they were going to induce emesis, with hydrogen peroxide. And what had happened is that the cat developed severe gastrointestinal signs, developing the Pros in the stomach. They ended up going for exploratory laparotomy, where they found about 60% of the gastric wall had necros, probably needing, resection, and then the owners had elected to have the cat euthhanased due to the guide of prognosis despite the surgery.

So that's quite an extreme case there, but really important to remember. This other study down below the effects of oral 3% hydrogen peroxide use as an emetic on the gastroduodenal mucosa on healthy dogs showed was a prospective study performing endoscopy after hydrogen peroxide administration in healthy dogs. And what they showed is, most of the dogs did have gas gastric ulceration, anywhere from one day to even up to a week post administration.

So it's something that I would, wouldn't recommend if you definitely have other methods of Mises. So how else can we, induce emesis other than apomorphine, particularly in our feline patients? So there's several studies looking at different agents, and comparing mainly xylazine with dexametlaomidine.

So I've basically just combined these studies and just given you these figures here. But they have found that xylazine has about 43 to 60% efficacy in cats. Side effects, sedation and reversal agents can include ghibin and apimazole.

Dexamettadomaine has 58 to 81% efficacy and can also be reversed with acetamazole. So if I'm going to choose one or the other, I would choose, Dexamedatomidine there. Sodium carbonate, so what we call washing soda crystals, it's not washing detergent.

I have seen severe ulcerative necrosis in the oesophagus and stomach from, a washing detergent, but this is washing soda crystals, so sodium carbonate. This is actually unpublished data, and, a criticalist had found that sodium carbonate has 61% efficacy in cats and 85% efficacy in dogs. And it's something that I have used previously, fairly commonly in Australia, in really busy emergency settings, and we often have several dogs being administered setting carbonate crystals.

I guess it's not. Not so commonly used in the UK here or or the or the US. And in the study, animals who had received sodium carbonate had gastrointestinal signs.

However, those gastrointestinal signs may have been due to original toxin or potentially the sodium carbonate. It was hard to, differentiate. But that's just from unpublished data, unfortunately.

And the other reported, emetic agent is, Epica serum. Next one is activated charcoal, so often enough, it means we might think about administering activated charcoal. So indications for use of activated charcoal includes toxins which bind to activated charcoal.

Drugs which are excreted in the bile. Toxins which have enterohepatic metabolism, we might want to give 4 doses every 4 hours. And we'll talk about some other toxins which actually have very slow hepatic metabolism requiring up to 48 hours of activated charcoal use.

If, you can get activated charcoal on its own or containing sorbitol. If it does contain sorbitol, only use it once. Sorbitol is a cathartic that causes osmotic diure diuresis, osmotic, movement of the gastrointestinal tract that includes gastrointestinal transit time, but it can also cause free water loss through the gastrointestinal tract, causing higher pernaremia, so high elevated sodium concentration in the blood.

It's also reported not only sorbitol, but activated charcoal alone can also have this effect, particularly if you're using it for a prolonged period of time. So it is important to monitor your sodium concentration of blood. It's contraindicated in recumbent unconscious patients with no gag reflex or seizuring, any neurological patients, .

I have, come across the use of activated charcoal as the, gastric lavage in, in patients. If they've had gastric lavage, we do it intubated anaesthetized and people put the activated charcoal via stomach tube in the, in the stomach. Myself, personally, I tend to stay away from that just in case the, the animal wakes up and regurgitates or vomits up the activated charcoal and puts them at risk of aspiration pneumonia.

However, I know it, it is a practise performed. And gastric lavage can be important for large volume, intestines of of particular toxins. I use gastric lavage more particularly with metaldehyde intoxication.

Things which aren't bound to activated charcoal, so the common toxins that we come across the ethylene glycol, alcohol, any alkali substances, petroleum, heavy metals, and xylitol. Diuresis is indicated when there's renal excretion of toxins or nephrotoxic toxins. Contrary indications include risk of fluid overload, so any patients who has aneuric or oliguric renal failure.

Patients with cardiac disease and pulmonary disease, and just be a little bit more careful with our feline patients. How we perform diuresis, we always say kind of 2 to 3 times maintenance rate, but we really have to think about like, how dehydrated is that patient? Do they have any ongoing losses?

So actually doing a, a more calculated fluid can may be important for these patients. And I'm not, I don't have time to go through, working out fluid plans. There's other resources for that.

But, the key point is have a think about it. And actually, It's actually unknown actually doing high diuresis is actually helpful or not. In the human literature, they talk about just making, putting them on maintenance fluids, just making sure that the kidneys are functioning is really the, the main thing, but we actually really don't know the actual fluid rate recommended.

I tend to go roughly about twice maintenance, but less if I'm concerned about fluid overload or more if they're dehydrated and then they have severe ongoing losses. Diuresis we perform anywhere between 48 to 72 hours depending on the half-life of the, of the toxin. And I like to monitor urea and creatinine, as well as performing a urine sediment exam every day looking for granular casts.

So granular casts are signs of tubular injury, which may be seen earlier than azotemia. If they do develop a urouric renal failure, you could consider using furisemide. There are arguments against using furosemide, saying that it doesn't really work and it can maybe cause some kidney injury.

I guess in my opinion, Here is that, you know, if they have auric oruric renal failure, and, you know, dialysis is not really an option for that patient and euthanasia really is the only other option I don't think it would hurt to try furosemide to see if that might help improve urine output there. Next one is dermal decontamination, pyrethrin toxicities. I'm not going to talk about in detail, but it is something commonly common that we see.

And if, owner has put on a spot on, I usually like to clip up the area where they put the spot on to remove as much of the toxin as possible in that highly concentrated area, and then to bathe the cat with, washing detergent. Pet shampoo doesn't work because of, the, the oiliness of the substance supply, so you do really need to use something a little bit harsh like the dishwashing detergents. So intralipid is the one which is in FAD at the moment, I guess, in the toxicology world, in the veterinary field, and it's indicated for toxins which are lipophilic.

And when we're thinking about how lipophilic they are, we look at the log P. So anything with a log P greater than one. And there's been a couple of review articles in JEC in 2011, which I got this table on the right-hand side, which have different drugs and the log P values, as well as more recently in the vet clinics of North America in 2018.

There's another lovely review article on the use of intralipid therapy. This vet clinics of North America in 2018 also reports on lots of different toxin topics. So it's a whole, a whole series on toxicology.

So have a look at that when you get some time. So, common things that we, we do see, which is, can be used, intralipid can be used as local anaesthetics. And this is actually where the use of intralipid therapy first came out.

They found it this in, in human hospitals that lidocaine overdoses. I wouldn't say common, but were, were reported. And I have actually seen a lidocaine overdose in my own hospital when a patient was on a CRI infusion, and there was a malfunction of the CRI, What do you call it, the, the infusion pump.

So the infusion pump accidentally gave it bolus because it was, there was a malfunction in the machine and required rapid intralipid administration. Amlodipine is another one. Amphetamine, methamphetamine, diltiazem, ibuprofen, ivermectins, and associated compounds which we'll talk about today.

The peramide, permethrins, as we've mentioned briefly, baclofen, which we talk about marijuana, microtoxins, tricyclic antidepressants, beta blockers, and calcium channel blockers. So they're all things which have been reported, to have intralipid use. When we're using intralipid, it's also important to think about what is a log pee of the drugs that we're administering to the patient to treat the toxicity.

So, for example, if you look in the table on the right hand side, diazepam has a log pee of 2.82. So perhaps you may be treating a patient, seizuring the diazepam, and then administering intralipid at the same time.

So think about If the intraloop is actually going to remove or help excrete the actual drug that you're using to treat the patient with. Some of the adverse effects of intralipid include lipemia, pancreatitis, hypersensitivity sensitivity reactions, and corneal lipidosis. To be honest, I haven't seen any of these things other than lipemia, but it is reported and particularly, Corneal lipiddosis is something that's been reported in this, particularly in this case report here, but it does, does go away after roughly about 5 days or so, so it's not a permanent lipiddosis.

So intralipid therapy, I give 1.5 mL per kg over 5 to 15 minutes, followed by a CRI of 0.25 mL per kg per minute for anywhere between 30 to 60 minutes.

And then I repeat this dose every 1 to 4 hours, depending on the clinical symptoms. If the clinical symptoms are resolved, then I don't repeat it. And each time I administer the CRI, I take a small blood sample and check the serum for any lipemia.

Antidotes, there's not that many antidotes, unfortunately, but we, if we take one step back, we have antidotes for a lot of the drugs that we use in hospitals. And often these drugs, if we have an overdose, I guess that's an intoxication. So think about this.

The opioids, we can use naloxone to reverse it, as well as the buorphenol, because buolphenol is an agonist antagonist. Benzodiazepines can be reversed with limazinil, meatomidine or dexametomidine with apiazole. Xylazine with apiazole as well as imin.

Paracetamol, you can reverse some of the effects of Nilocysteine. Serotonin syndrome with suprahepathy, and we'll talk about serotonin syndrome today. Asglycol with omeprazole.

Or alcohol, non-steroidals with misoprostol. So I guess it's not a complete antido dope. But misoprostol is a prostaglandin analogue, so it's a great astro protection with NSAID intoxication.

And muscarinic mushrooms, organophosphates, and carbon weights with atropine use. So, now we're going to talk about different Types of toxins, we're going to cover, I think roughly about 6 different toxins and ones which have been reported recently in the literature. The serotonin syndrome, there's a lot of reports of serotonin syndrome these days.

I think it's due to increased use of, you know, things like antidepressants and, you know, amphetamines and things like that, medications which humans are on. And when we're thinking about serotonin syndrome, there's 5 different mechanisms that this can occur by. This particular diagram is from the Small Animal Critical Care Medicine textbook by Sylva Stein and Hopper, and it's the first edition there.

And it has a great section in toxicology. The second edition doesn't because it's more critical care focused, but if you want to look at, the toxicology, go back to the 1st edition. So If we're going through the 5 different mechanisms, the first one is increase in tryptophan administration.

And tryptophan is metabolised to serotonin, hence causing serotonin syndrome. The second one on the left-hand side is amphetamines. So amphetamines cause increase in serotonin release from the presynaptic neuron.

Serotonin is. Metabolise. And by monoamine oxide.

And so if you have a decrease or inhibitors of monoamine oxides, such as antidepressants, certain antidepressants, and Parkinson's medication, you have decreases in serotonin metabolism, resulting in increase in serotonin in the presynaptic neuron. The tramadol, opioids, and tricyclic antidepressants as serotonin reuptake inhibitors, which results in increasing concentration of serotonin in the pre-synaptic neuron. And finally, things like LSD and lithium, which is not so commonly used these days, and results in serotonin, increase in serotonin agonism at the postsynaptic neuron.

But overall, all of these toxins can result in serotonin syndrome. These are just some of the reports that I found in the recent literature including serotonin reuptake inhibitor antidepressants in 313 dogs. Same with 33 cases in cats.

Presume cocaine toxicity in 19 dogs, Mirtazapine toxicity in cats, I think about things like iatrogenic toxicosis, as well as the tramadol toxicity in a cat. The clinical signs we see is gastrointestinal, vomiting, diarrhoea, as well as most commonly we would notice the CNS stimulation. You can also get cardiovascular system abnormalities including arrhythmias and hypothermia.

Diagnosis, is by, you can, is by taking a really good history. So history taking is really important when we're thinking about toxicities and being very specific when we're asking the owners about the particular toxins. So it's really important to know what toxins cause certain clinical signs when we're taking your history.

Ultimately, you can perform a urine drug test, and this has been validated in dogs, but not in cats, but I'm assuming that you could use it in cats as well. And it tests for barbiturates, opioids, benzodiazepines, amphetamines and amphetamines, and phenylcyclidines, cocaine, and marijuana. Treatment includes use of activated charcoal.

And if they're showing signs of serotonin syndrome, you want to give a serotonin receptor antagonist. You can use ippraheptadine or chlorpromazine, although in the human literature, it's showing that ciproheptadine is more efficacious than the clopromazine. So if I was going to choose one or the other, I'll go for the ipraheptadine.

If you're considering having to sedate the patient, you can use aceramazine, because as long as the sedative and anxiolytic inhibits dopamine release, and also is an alpha-adrenergic blocker. So it can actually help with some of the clinical signs of serotonin syndrome as well. If they do develop an arrhythmia, beta blocker is preferred over the diltiazem because the tiazem use in these particular patients can cause hyper seizure and dysphoria.

And the good news is, with all of these reports, all of these dogs and cats have had 100% survival rates. So although the clinical signs are quite distressing and severe, most of the time, I would say they would, have, a good outcome. Another one which I've, actually fairly commonly come across is baclofen toxicity.

So this is a muscle relaxant. It acts on the Gabba presynaptic receptors inhibiting glutamate and aspirate, sorry, aspartate, resulting in an essentially acting skeletal muscle relaxant. It also inhibits substance P, which reduces myocardial adrenaline and no adrenaline.

It has a peak plasma concentration within 2 to 3 hours after ingestion and a half-life of up to 6 hours. And one thing to remember and take note is at 70 to 85% of this toxin is excreted by the kidneys in its active form. So administering, urine diuresis is important.

This is a retrospective report on backoff and toxicity in dogs and cats of 145 cases. 5 of those were cats and the rest were a dog, I have to admit. But clinical signs include ataxia, CNS depression, agitation, vomiting, diarrhoea, hypertension, bradycardia, meiosis, and also there's a risk of hypoventilation in these patients due to the muscle relaxation.

Treatment includes atropine, midazolam, methocarbamol, and this is actually an interesting and important thing to remember is that with blo of withdrawal, sometimes they can get serotonin syndrome. So look out for the clinical sciences serotonin syndrome that we just talked about, and you can consider using ropine in these cases. Intravenous fluid therapy because it's been like treated in its active form.

It has a high look piece so you can use intralipid. And also you can use hemodialysis as well to help remove this toxin. Next one is, a bit of an oldie, but we still see it fairly commonly these days, and there's lots of reports in the literature is the ivermectin intoxication.

When we're talking about ivermectin, we're also talking about other toxins such as ellamectin, moxidectin, ivermectin, and milvamycin. And what it does is inhibits the GABA neurotransmitter, causing neuromuscular blockade. And collies with the ABCB1 gene is more susceptible due to abnormal metabolism of these drugs.

The clinical signs are CNS depressant, ataxia, paralysis, hyper seizure, seizures, coma and death, and also retinopathy has been more commonly reported. The clinical signs are often worse with the lower body condition score. In regards to treatments, there's a lot of reports on using intralipid therapy use.

So there's this one in 20 cats with vain to overdose of ivermectin. This is another one in a cat. And actually, this is an interesting recent case report on use of Intralipid in a dialysate into two dogs.

So these two dogs developed hyperventilation, required mechanical ventilation. So they were on the ventilator for 2 days, and they received dialysis using inch lipids. So, and had successful outcomes.

So, so that's quite interesting. These More recently, there's a lot of reports on retinopathy, so retinal edoema, and this is a case series of 5 cats. There's a case report here, using intralipid therapy to treat the ivermectin-induced retinopathy.

So usually it would take about 5 days to clear, clear up, so they have loss of vision, etc. But with this particular dog where they use intralipid therapy, the, the vision improved after 90 minutes. So that's, that's a consideration when we're treating our patients.

I don't know if you can appreciate in this diagram on the right hand side that the, the figure or the picture on the left-hand side is one with retinal edoema, and the one on the right is after it's had its treatment and the retinal edoema has resolved. Next one we'll talk about is non-steroidals. So non-steroidals, inhibits the cyclooxygenase, either COXS1 or COX2 or both in the acadonic acid pathway.

And basically what it does, it causes, gastrointestinal ulceration, acute kidney injury, and platelet dysfunction. I know most of us have probably treated non-steroidal intoxication. I just want to briefly touch on the more recent reports on the treatment recommendations for non-steroidal use.

This study in 2015 compared to use of multi-dose activated charcoal, because there is some antirhepatic metabolism, single dose activated charcoal versus activated charcoal with sorbitol use as a single dose. And actually, they found no difference between all three groups, and the overall recommendation from the study is actually perhaps any single dose of activated charcoal is necessary. There's use of intra intralipid use reported in 3 dogs with naproxen overdose because it has a high lope.

And this case report down below, treatment of ibuprofen toxicity with serial charcoal hemafi fusion. So that's using dialysis with a charcoal cartridge. And followed by hemodialysis in a dog because it developed acute kidney injury.

So that's another interesting way that we can treat, severe non-steroidal. Intoxication. So here, now we'll talk about rodenticide, intoxication, another common one that we've always seen, and I'm sure most of you have treated rodenticide intoxication.

But there's 3 different types, so we're actually going to talk about the 3 different types of rodenticides. So anticoagulant rodenticides, bromethyline, and finally, Vitamin D or cho a calciferol. I put this little picture on the right hand side, because I think if you do have rats or mice, and what you can recommend to your clients is there are humane mouse traps that you can purchase, which aren't going to harm their pets.

And this one I found on the internet is a homemade humane mouse trap. I've used humane mouse traps, not homemade ones, because I'm not that skilled at building things, but, you know, it has worked, and then I just, went to release the little tiny mouse. So there you go.

So first of all, the anticoagulant rodenticide, this is the most common one that we come across. It inhibits vitamin K dependent coagulation factors including 279, and 10. And that's really important to remember.

There is a first generation ones, including warfarin. And what actually they found is that some rats or mice had resistance to warfarin. And so then they developed the second generation ones, including rediicum and redone.

A lot of difficult to pronounce words in, in, in toxicology. And finally, the indone, including chloro. I can't pronounce this one Chloro Fasinone and Fainone.

And they're kind of similar to the second generations in regards to the situation, etc. When we're thinking about anticoagulant rodenticide intoxication, they present either as acute ingestion or they present with signs of clinical bleeding. So if you come across one with acute ingestion, it is indicated depending on when they ingested it and activated charcoal, and it does have enterohepatic metabolism.

So you can do 4 doses every 4 hours or until the faeces is showing, the black charcoal. The question is, do we give vitamin K to these, these particular Patients, vitamin K is very expensive, but if they have ingested the toxic dose, and you think, OK, despite emesis, because emesis only really removes about 60% of the ingestor in the stomach. So if they have ingested a toxic dose, I personally would give vitamin K.

If they've ingested the 1st generation one for 1 week, if they've ingested the 2nd generation for 4 weeks, and to check the PT. 48 hours after the last dose. If they've ingested a sub-toxic dose, this is my personal opinion, is I would recheck the PT in 48 hours and then make a decision if you want to administer vitamin K.

Cause if you think about if you've got like a 60 kg dog and you need to give vitamin K for 4 weeks, it can be very, very expensive. In the meanwhile, what I always recommend to the client is no rough play with other dogs, don't feed any, any bones, And just minimise any trauma as much as possible and minimise the risk of bleeding to that patient. The reason that we check the PT rather than the APTT is that vitamin K dependent coagulation factor including factor 7, has the shortest half-life.

So you have a prolongation in PT before you see a prolongation in APTT. So if you have a patient who's presenting with signs of bleeding, I think all of us are quick to do check the PT and APTT and also a platelet count. If you have prolongation in PT and no prolongation or normal APTT, you're more than likely going to have anti factor, sorry, vitamin K deficiency.

Due to anticoagulant rodenticide ingestion, the other potential differential would be a factor, congenital factor 7 deficiency. You could also get a prolongation APTT as well, depending on where the, when the, the patient ate the ingested the anticoagulant rodenticide. We do sometimes see thrombocytopenia, and that can be the confusing factor, but the thrombocytopenia, it can occur due to consumption of the platelets while the blood's trying to clot.

The definitive diagnosis is using spectrophotometry, which has to be done 3 to 5 days after ingestion. And to be honest, I, I haven't actually done this before. I find that I have taken good history and looking at the, the difference in PT and APTT has been fairly sufficient to manage these patients.

Clinical signs includes bleeding. So if we're looking at, different in coagulation factors, we're more likely to have cavitating effusions. Bleeding into the lungs can be quite severe, bleeding into the pleural space can be quite severe.

So often these, these patients present with respiratory signs. In regards to treatment, we always think about administering fresh frozen plasma or fresh whole blood for the coagulation factors. But one thing to remember, if you only have stored whole blood, or you have frozen plasma.

So frozen plasma is fresh frozen plasma which has been defrost and refrozen immediately, or fresh frozen plasma, which has been passed its one year expiry date. And these products still have. All of the coagulation factors except for 5 and 8.

So it has all of the vitamin K dependent coagulation factors, so those can be used. If you have consumption of other factors like factor 5 and 8, maybe the other other ones will be better. So I would still probably pick the fresh frozen plasma or freshhold blood.

But if you don't, then use your soilhole blood and frozen plasma, and it will have some effect. The reason I wanted to talk about the anticoagulant rodenticide is that there's been some reports recently causing upper airway signs. So, this one on the left-hand side is anticoagulant rodenticide toxic toxicity causing tracheal collapse in the 4 small breed dogs.

And as you can see, it's got severe tracheal narrowing. And some of these, for dogs had either intraluminal haemorrhage or extraluminal causing some compression. The one on the right is 5 dogs with upper airway obstruction, secondary to anticoagulant rodenticide toxicosis, and you can see around the laryngeal area, there's quite a significant obstruction there.

So have a think about anticoagulant rogenticide as a cause of upper airway obstruction in dogs. This is another interesting one that I kind of came across, an apparent case of Bredicuum toxicosis in a whingon. And the interesting factor about this one, it had normal PT and APTT.

So it's important to think about when we're using these tests is what's the sensitivity of specificity of, of these particular tests. So, You have to get a, a reduction in the coagulation factors of greater than like 75% to actually get, prolongation, so 25% to get prolongation in PT and APTT. So maybe that have affected it.

But what had happened in this particular dog, they were performing a caesarean section, and, there was a significant bleeding everywhere. And the PT and APTT were normal. They, they sent the dog for postmortem, examination, and they also checked the, checked for any, redivium levels.

And actually, they found that this, wing bitch did have redivium. In her system, and which probably cause, caused the bleeding. The other interesting thing reported in this is they also checked the pups and they found that the bolife has crossed the placenta.

So that's something to remember, in ingestion of, pregnant bitches. The next one is choliccalciferol or vitamin D intoxication, and it's some, getting a little bit more common that we see this type of rodenticide toxicity. So vitamin D is metabolised to calcipidiol, which is then metabolised to calcitriol.

And with the choliccalcifey intoxication, we have high levels of calcifediol in the, in the blood system, usually about 10 to 15% higher than what you would normally find, and calcitriol levels is about 3 times of what we normally find. So it ends up in that second stage most. What it does is it enhances calcium and phosphate absorb absorption from the gastrointestinal tract as well as the distal tubules of the kidneys and bone.

In addition to finding it in rodenticide, we can also, it has also been reported from intoxication, vitamin D intoxication from human medication, creams, and also pet food. The clinical signs are associated with hypercalcemia and hyperphosphatemia, including PUPD, neurological signs, and then just very non-specific signs. And these non-specific signs can also include mineralization from the kidneys, gastrointestinal tract and the skin.

Diagnosis is by measuring ionised calcium, hypercalcemia, hyperphosphateemia, and you can send, by the way, for parathyroid hormone and calcipidiol. And just performing, you know, for. For examinations and diagnostic imaging, and you might see some mineralization in particular organs.

The treatment, if they're asymptomatic, includes charcoal, and repeated charcoal due to enterapatic metabolism. And because it's highly bound to bile, they have recommended cholestyramine, which binds the bile which prevents reabsorption from the gut. And it's important to monitor these patients for 4 days.

The calciarol has like a very long half-life and monitoring ionised calcium phosphate, BUN and creatinine daily for 4 days in hospital. If they are symptomatic, we may need to treat for more than like 1 to 2 weeks because it has a very high half life. And the treatment mainly is a treatment for hypercalcemia and hyperphosphateemia.

So using sodium 0.9% sodium chloride, furosemide, glu glucocorticoids, sodium bicarbonate. Permidronate, which is the bisphosphonate or calcitonin.

And phosphate binders. The, the final rodenticide rodenticide is brometholin, and there's been more frequent reports on this. And basically, what it does, it's a neurotoxin which inhibits mitochondrial ATP production in the brain, affecting the sodium and potassium channel pumps, and leads to electrolyte imbalances and fluid shifting to the brain and the spinal cord.

So really showing neurological signs. It has a wide distribution in the body once ingested. It's highly lipophilic.

It's very slowly excreted from the bile and has enterhepatic metabolism. And half, the half-life in rats have been reported to be 5 to 6 days. The clinical signs of this is interesting and important to remember.

So if they've ingested a high dose, you'll see neurological signs almost immediately, so about 4 to 18 hours after ingestion. And in low dose you can see paralytic syndrome. So, and this can occur about 17 days after ingestion, including ataxia, depression, upper motor neuroenzymes, and, and coma.

The other interesting thing is that cats can develop abdominal distension due to ileus. So think about that being a differential. In cats with alias.

And other signs report including, includes vomiting, diarrhoea, hyper seizure, hypothermia, extension extensive rigidity, and cranial nerve signs. And diagnosis can be performed by serum, this methyl, bromethyin, and as I've mentioned repeatedly, making sure you get a good history. Going back to intralipid therapy again, bromethyline has a high lope, and so there's one report of use of intralipid use in bromeyle toxicity in a dog.

Saying that this particular dog didn't have any clinical signs, so the use is still questionable. But I think there's not much harm in using intralipid therapy in anything with Hylo PE just because it hasn't been reported, thoroughly doesn't mean that it doesn't work. And in my opinion, I would use it.

Other things for treatment include Eises activated charcoal, and this is repeatedly for 48 hours they recommend. And because you're using activated charcoal every 4 hours for 48 hours, it's important to monitor your sodium concentration, as sodium changes in the brain can cause neurological signs also. And as always, treat the patient for the neurological sign.

So finally, I'm just gonna end with a little bit of a fun one. Mushroom intoxication has been reported more commonly these days. And when I think about mushroom ingestion, I think of, dividing them up into 4 different clinical signs.

So he hepatotoxicity, muscarinic signs, so they're probably the two most common ones that we see, nephrotoxicity and gastrointestinal irritation. The most common one that we come across is Amanita mushrooms, and this is a case report of two cats with acute hepatic and renal failure secondary Amanita ingestion. Amineta binds to RNA polymerase 2, which diminishes protein synthesis resulting in cell death.

And the reason that the liver and kidneys are most affected is due to the higher rates of protein synthesis in those organs. There are 4 stages of clinical sign. The first one is the latent period of 6 to 12 hours.

And this is really why, you know, the owners might notice that the animals are eating mushrooms. They think, oh, OK, they're fine. Nothing's really happened.

It might be just something really benign, not realise that actually these mushrooms have this latent period, and you don't see gastrointestinal signs until 6 to 24 hours. You then have this false recovery period where they seem fine for 12 to 24 hours and following that get full minute hepatic and renal failure. So that's why it's, it's quite a deadly mushroom.

Diagnosis is by mushroom identification, and also you can check alpha amineetin levels in the serum, urine, gastric contents, and also kidneys if you're concerned. When we're performing a mushroom identification, they recommend doing this mushroom print on white paper, sending that off as well as sending the mushrooms in a brown paper bag. These are the different mushrooms causing amanita toxicity including Amanita, yoides, arina and Lepiota casania.

And treatment for Amanita ingestion is Esus single dose activated charcoal. And also you can consider giving milk thistle which reduces the uptake of amineitins into hepatocytes. In dogs, you can use penicillin G, which would also reduce uptake into hepatocytes.

But in humans, penicillin G doesn't work, and so in cats, we're actually unsure if penicillin G is actually efficacious in reducing uptake by the hepatocys. The next one is muscarinic mushrooms. So there's a case series of acute innery mushroom toxicosis in dogs, and there's a report of suspected muscarinic mushroom intoxication in a cat.

And basically mascar biance acetylcholine receptors in the peripheral nervous system. So the two common species of mushrooms include crioy, as well as innery there. And you can see it's just so hard to tell what mushroom is what, and so it's important to do this, perform the mushroom identification as discussed earlier.

So when we're thinking about these muscarinic signs, I think about the pneumonic dumbbells, so diarrhoea, urination, meiosis, bronchorrhea, bronchoconstriction, emesis, a cremation, and salivation. And remember the other differentials for the dumbbells is organophosphate or carbamate intoxication. Treatment really is by atropine, and so they recommend giving 0.04 mg per kg, a quarter of this dose IV and 3/4 subcu or intramuscularity, and you should see improvement in clinical signs within 30, 30 minutes.

And finally, this is the, the final report. I'm going to mention is a respiratory arrest following ingestion of wild mushrooms in three dogs. And They reported seeing ingestion of mushrooms with these dogs, and some of them vomited that mushroom.

One of the three dogs had the mushroom identified, and it wasn't, shouldn't have been one that caused respiratory arrest. I do have some doubts about this particular case series. Was it actually the mushrooms which caused respiratory arrest or something else?

But nevertheless, since it has been reported, if you have a dog or cat that's ingested mushroom, it's important to monitor their respiration, just in case they do have respiratory arrest. And basically, these 3 dogs, 2 of them, actually all of them went on mechanical ventilation. One of them was euthanased, and the other 2 survived after 24 hours of mechanical ventilation.

So it was only just a short period of, of mechanical ventilation. And finally, we talked a lot about toxins. We talked about approaches to patients with intoxication.

We talked about different specific toxins, and from those different specific toxins, I did branch out into other aspects of toxicology from that. So I hope you got some information. From that, but more, most importantly, when we have an intoxication or toxin ingestion, always remember to treat the patient first and then treat the toxin.

I've put this finally here, just different sources of information that you can get. I already mentioned the, small animal critical care medicine textbook, sorry, I haven't popped it on here by Silverstein and Hopper. The first edition is better than the second edition when we're talking about looking at toxins.

I quite like the small animal toxicology 3rd edition book by Peterson and Talcott, has, a lot of great information there. I find, V. The Veterinary Information Network very, very useful on looking for more unusual toxins, and they have a toxicology board there where you can ask questions and you can get replies by other vets and actually other veterinary toxicologists.

And in the UK, the VPIS can be very helpful in also unknown toxins and how to approach those toxins, as well as in the US, the pet poison helpline, ASPCA. And also Google can be very helpful if you're looking up things of like things that you've never heard of before or you're wondering, what is the logpe for that? Can I use intralipid?

I often just Google the, the toxin and logpe and it can give us, some very useful information there. And so I would welcome any questions, that you can email through and I will answer them as quickly as possible. Thank you very much for your attention this evening.