Potions and the dark arts: the latest from eTG Toxicology

Hi, and welcome to this episode of Australian Prescriber. I'm Dr Justin Coleman, a GP on the Tiwi Islands. Just head south from East Timor, turn left at Darwin and there I am.

Today, I'm delighted to have one of my favourite topics on this podcast, and that is toxicology. With us today, I have Venita Munir, who's a former emergency physician and now editor of Toxicology and Toxinology, which is the latest of the Therapeutic Guidelines books. Although in this case, it's not physically a book because the eTG from now on are going to be published online only.

Welcome to the podcast, Venita.

Thanks, Justin.

One of the reasons I do love toxicology is it's all about poisons and that they go way back to Shakespearian days, I think. Romeo and Juliet having theirs, and Macbeth and Hamlet's sword, probably even earlier, Socrates, I think, was poisoned with hemlock.

Here's my first question. What's hemlock, Venita?

Oh. Well, that's a very difficult question for me because I don't actually have that in my guideline.

That's all right. I'm sure Socrates is most grateful.

I do have a poisons book that I could look it up for you. It's some sort of plant-based poison. But I don't think we really have it in Australia, so it's not in my guideline.

Not many calls to Poisons Information Service. So being a plant-based thing that would be toxinology, is that right? Is that the difference between toxicology and toxinology?

Yes, that's right. Toxicology is dealing more with your average poisons and other substances, whereas toxinology is based around toxins, so toxins from animals and plants.

Let me ask you a second question, Venita. Is it true that Harry Potter has revitalised the toxicology industry, in the same way as COVID has done for the virology industry?

That's quite possible. I've been watching a lot of Harry Potter recently because I have a 12-year-old daughter, and there certainly are a lot of very interesting potions going on in the dark arts there. I'm sure there's a whole generation of people who are going to think it's pretty cool and sexy to be a toxicologist in the future.

They'll be hanging out to find out what Basilisk venom, what the toxin in that is, I guess.

Even more in the news recently, there's a new show out on, I think Novichok was it? Was that the Salisbury, the Russian, I was going to say toxicologists, the Russian users of poisons killed a Russian agent and his daughter, I think, in Salisbury?

Oh, yes. Yeah. Was that one of those nerve poisons or radiation poison?

Yeah.

And there was something about the... Is it the opposition leader in Russia who's been poisoned recently as well?

Yeah, that's right. There's all sorts of goings-on over there, which would keep toxicologists well employed in Moscow, I would imagine. We probably should move on to your book. Enough banter.

One of the updates in the guidelines is about the highly toxic agents and there are various mushrooms and medications, which are rare but highly toxic and they've been updated, I gather?

Yes. We have added a whole lot of new material to the guidelines that wasn't in the previous version. So we have a number of totally new guidelines, including ones for the death cap or Amanita phalloides mushrooms and lots of other really nasty herbicides, paraquat and glyphosate, and then other insecticides, all hydrocarbon agents.

Then we've got some other weird and wonderfuls like isoniazid, the TB drug, and local anaesthetics, gabapentinoids and the newer antipsychotic agents like quetiapine.

Even good old paracetamol has an updated section for what you call repeated supratherapeutic ingestion. I assume that's where the person sort of takes more than eight tablets a day on a long-term basis.

Yes, that's correct. It's generally where people are unintentionally taking paracetamol because they’re unwell. Usually, they'll have pain or fever and they don't actually know that they're taking too much. Or they're taking multiple preparations that contain paracetamol and they don't realise that they're taking double the dosage, such as these combination products with pseudoephedrine or codeine or even ibuprofen.

Yeah. Look, you can certainly see how that does happen with the plethora of medications containing paracetamol on the market.

The other thing that strikes me is now with the slow-release preparations, and I guess this is a question generally for slow-release preparations. is it generally more dangerous to ingest excessive amounts of slow-release tablets, rather than the immediate release?

Not necessarily. It still is dependent on the dose that the person takes. I mean, paracetamol poisonings, as you would know, it's lucky that we have such an effective antidote in acetylcysteine. Because paracetamol also happens to be the most common poisoning within Australia and is still available freely over the counter at any old 7-Eleven, as well as supermarkets and pharmacies and so on.

So immediate-release preparations, you generally go by the paracetamol levels and work out what sort of treatment guided by the paracetamol toxicity treatment nomogram. The modified-release preparation, it's actually a combination of immediate-release and modified-release. So, in fact, for the modified-release preparations there's a completely separate treatment flow chart. We actually have five different paracetamol poisoning monographs now in the toxicology guideline.

Then some of the other medications, also the common ones would be some of the antipsychotics and certainly things like quetiapine, I think, are used and sometimes abused as well, whether intentionally or unintentionally. Some of them even have a street value, so I guess it's important to have an update on those.

Yeah, it is. Previously there was a topic on antipsychotic drug poisoning. But because of the difference between the older style antipsychotics and the newer antipsychotics and their different risk profiles, we separated them out, so that there's now a general topic on all antipsychotics. Then we have four separate ones on the newer ones, so there's amisulpride, clozapine, olanzapine and quetiapine.

For instance, amisulpride poisoning causes more cardiac issues with QT-interval prolongation and arrhythmias. Quetiapine, as you were saying, does have some street cred, and people have been selling it on the street as a sedative, I suppose. Basically it's about managing the sedation and the potential for respiratory depression and aspiration pneumonia.

Okay, so primarily sedation for the antipsychotics.

For the hypoglycaemics, is the main issue there just the low blood sugar, and the clearly very serious risk, even of death in fact, it can entail, or are there other specific things for the hypoglycaemics?

Well, for insulin and sulfonylureas, certainly it's mostly hypoglycaemia that's the problem, particularly for insulin poisoning. For metformin poisoning, metformin itself doesn't cause hypoglycaemia, but it can lead to a pretty severe metabolic acidosis and make people pretty unwell with that and might require intensive care and haemodialysis.

Excellent. Lots of new stuff in this latest eTG Toxicology.

Moving away from pharmaceutical drugs now and onto some of my favourite little critters, so we've got snakes and things that sting and bite and poison, ultimate Australian topic, I guess. This has been a bit of up and down over the years, in terms of how much antivenom to use and whether to use it and when to use it. The current guidelines, what do they tell us about the steps in managing snake bite?

Okay. We updated it to really put the emphasis on determining whether your patient has clinical or laboratory evidence of systemic envenoming. Then if that is the case, then you determine which antivenom might be indicated, determining which snake group is the most likely to be responsible going by the geography of where you are and what snake species are endemic in that area. I mean, it's always preferable that if you know exactly which snake you're dealing with, that you would give the relevant snake antivenom. So you might give a tiger snake antivenom or a black snake antivenom, or a brown snake antivenom.

But in most scenarios, people don't know what snake they've been bitten by, or it's notoriously difficult to identify a snake from a description. The current recommendation is actually to give two vials of antivenom. This is at least for the eastern seaboard of Australia, and that would be one vial of tiger snake antivenom and one vial of brown snake antivenom. Those two antivenoms will cover most significant snake bites in the eastern part of Australia.

There are different recommendations for places where there are other species predominant. Say for instance, in Tasmania, they only have tiger snakes, so you would give one vial of tiger snake antivenom, or in Western Australia, they have more black snakes and tiger snakes. In the northern part of Australia and where there are taipans and also where there are mulga snakes and death adders, well, then you would go for the polyvalent antivenom because then you really are faced with different snakes that don't occur elsewhere.

I think up where I live, the reason you can't detect what sort of snake it is, it's because it's usually eaten by the locals by the time you try to find out.

Is that right.

It's quite a delicacy up here.

Right.

I know we don't test so much with venom detection kits anymore. Is that right?

No. Toxicology and Toxinology group have actually said that the venom detection kit is no longer recommended.

There's also antivenom no longer recommended, I think, for red back spiders and box jellyfish, at least, for the intramuscular immediate antivenom. We're moving a little bit away from antivenoms?

Yeah. In red back spider bite, the RAVE-II study showed that red back spider antivenom was actually only minimally better than analgesia for the treatment of red back spider bite. In fact, again, the Toxicology and Toxinology expert group decided to no longer recommend its use, unless there's really specific circumstances where the patient has ongoing pain and are not responding to parenteral analgesia.

Regarding box jellyfish sting, there was a move towards paramedics giving intramuscular box jellyfish antivenom at the scene. Unfortunately, what this meant was that people weren't then doing adequate CPR and there were more delays getting the patient to a definitive emergency department. The patient's survival really depends on adequate CPR and getting them into a hospital for intravenous antivenom. That is much preferred to mucking around on the beach and giving intramuscular antivenom that doesn't actually reach the circulation for a long time, anyway.

Thank you. Well, moving on from things that bite and sting and slither and swim to button batteries. With button batteries, we're looking at serious adverse events very quickly within two hours, which surprised me, and you need to get an x-ray fast.

Yes. Unfortunately, there have been a few small children who've ingested button batteries that weren't picked up for quite a long time, and they've died from catastrophic consequences of aortoesophageal fistulas and horrible things like that. So there's a real push to try to identify button battery ingestions a lot earlier because they can actually perforate the oesophagus within a couple of hours.

Management priority is to make sure they have a high triage, that they don't just sit in the waiting room for ages waiting for investigations and things, but that they actually get a prioritised time-critical neck-to-bottom x-ray. That is an x-ray of their neck, chest and abdomen from triage, and then an urgent referral for endoscopic removal of a battery if one is seen on the x-ray.

Yes, very important. I've often wondered, is there something intrinsic to button batteries that gets them stuck more often than most other things in the oesophagus? Because not many things get stuck in people's oesophagus. Or is it just that if they happen to get stuck there, they cause catastrophic damage?

A bit of both. There are so many different button batteries available these days, and they come in all different shapes and sizes. So the larger they are in diameter and also thickness, obviously, will mean that they have the propensity to get stuck at the gastroesophageal junction. If that's the case, then they almost immediately set up a caustic type of injury. It can burn through the oesophagus very quickly. If the battery's in the stomach, they generally will pass through the gastrointestinal tract.

I think we might finish now on one of the other sections, which has been updated, which is the recreational drugs. I guess that's something that always has to be updated because they move fast. In fact, where I live init's, certainly in the top end, I think there's a bit of a problem with some of the synthetic cannabinoids being smoked. Around here, they call it Kronic with a K, I guess K is cooler than a CH, and smoke a bit of that. But it must be hard to keep up with all the different recreational drugs and keep up with the advice about each of them individually.

Yeah, that's right. There are just so many new and novel drugs on the market. We've written some new material for the guidelines about these, but even so, there's an awful lot of crossover between these drugs as well. Often they are not what they said they are meant to be, and often they have very similar effects. So one drug, they might think that it's a hallucinogen, but then it actually is a stimulant or vice versa. So they're really tricky drugs, and there's just hundreds and hundreds and hundreds of these drugs coming in, mostly from China, but also from Mexico, into Australia.

So we have some new topics on these drugs with all the new types of amphetamines, the cathinones, which are other novel stimulants, the synthetic cannabinoid receptors, as you mentioned. They are often just sold in packets of leaf that is sprayed with the drug and smoked. There's so many of these drugs that they can't be made illegal because there's so many of them churning through that they can't keep up with what each one is and how to ban them.

Also in our recreational drugs, we've got some other updated monographs on the stimulants. We've got new monographs on cocaine, a new monograph on buprenorphine and few other interesting things like GHB. There's an awful lot, an awful lot of new stuff in there, and I suppose it will just be on the day if someone presents, you have a look in Toxicology.

It must be a wonderful position being one of the Australia's experts on recreational drug use, and you've written the book about it and …

Not quite. No. No, working at St Vincent's probably gave me a little bit more information on recreational drug use.

Very true. It has been a delight talking to you today, Venita Munir, and thank you very much. I think it's a wonderful resource for GPs. It's the sort of thing which we really do need to look up where, as long as you're aware of the broad categories as a GP, I think, the finer detail, you probably only need to look up each particular chapter once in a blue moon. But by George, it will help you on that day and help the patient in front of you. So I think it's a fantastic resource, and thanks very much for coming on …

Thanks.

... our podcast to speak about it.

Thanks, Justin. Thanks for having me. I do hope that it is helpful to a lot of clinicians, particularly in the rural and remote areas who might not see these things very often. But when you do, you want to know how to treat them in the best possible way.

Thanks so much.

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My guests' views are their own and don't represent Australian Prescriber, and my views are certainly all mine.