Deadly Digitalis - Periodic Table of Videos
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- Опубліковано 6 січ 2023
- Professor Rob Stockman discusses Digitalis - used to save heart patients and poison spies.
More links and info in full description ↓↓↓
Rob Stockman at the University of Nottingham: www.nottingham.ac.uk/chemistr...
More videos featuring Professor Stockman: • Rob Stockman - Periodi...
An Account of the Foxglove and some of its Medical Uses by William Withering - www.gutenberg.org/ebooks/24886
Videos on all 118 elements: bit.ly/118elements
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From the School of Chemistry at The University of Nottingham: bit.ly/NottChem
This episode was also generously supported by The Gatsby Charitable Foundation
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Poisons have a long history of being used for medical treatment. We use opium poppies and cone snail venom for pain relief. We use colchicine for gout. We treat breast cancer with paclitaxel which comes from the Pacific yew tree. We treat acute leukemia with small amounts of arsenic. What makes a poison is the dose.
And oncology drugs are usually complex cytotoxins
but I still prefer nitroglycerine
nah dude poisons are things that can stop cellular respiration or otherwise stop your cells from getting energy.
@@simonlinser8286 so Botulinum toxin, incidentally called Botox and used for medicinal and cosmetic purposes.
Yeah, like Simon says, cyanide (for example) is just a poison. However, one the same note as your post, cyanide ions can be floated around an iron atom and you've got nitroprusside, a medicine that fights hypertension...
Foxgloves (Digitalis) are my favourite flowers. I have loads in my garden every year, they grow to around 6ft tall!
Great episode. Been a while since we had Prof. Stockman on here. Took me a moment to recognise him, and found he resembles Daniel Craig enough to allow for the fiction that he is James Bond working as an organic chemist in Q’s laboratory after retiring from active field duty. :)
Hahaa so true, his resemblance to Daniel Craig is really striking. Also the voice :)
this guy is my lecturer, nice bloke
We were sent a missive if not an epistle from health and safety at Herts County council, informing the school of all the chemicals that under no circumstance were we to have.
Chemistry technician checked and found the lot, every single one, starting with the arsenic compounds, right down to thallium. Headmaster, being a chemist of some note, was OK with that, and binned the letter.
As long as the scientists were well qualified, politicians should keep their noses to themselves imo.
@@chrispycryptic At a school you never really know whether the chemistry teacher is passionate enough about chemistry to really care, so it makes sense that the council wants them to get rid of dangerous chemicals.
@@Kenionatus
In an undergrad academic setting I definitely could see it potentially being an issue honestly... I just find the destruction of unique chemicals to be a sad situation...
Always fun to find old chemistry treasures! I've gotten ahold of a few from antique shops
where i did my apprenticeship we had a drawer labelled "danger, open carefully". nobody ever put anything in it or took anything out. when we did a big cleanup of the lab we opened it. turns out someone instead of properly disposing of the old mercury thermometers just gather all of them and put them in that drawer.
@@saladiniv7968 nice find i would say.
Wow.
The rigidity of the steroid structure is in the name, but only incidentally. That "ster" means 'solid: ie. rigid', and that is present in e.g. "stereochemistry". Steroids were named after "cholesterol", which was found in gall stones, which are solid!
Ah and probably steridian too
Thank you to everyone on the cast and crew for making these videos.
For sure, I've learned a lot of chemistry facts from these vids
As a Pharmacy Technician I loved learning about Digoxin... Foxgloves are my fave plant to grow. For those who don't know, 'Digitalis' means 'finger' (ie a digit) and comes from the German for Thimble which the flowers resemble.
My professor used to be fond of reminding us of the origins of our modern formulary of medicines and their importance in early 'potions' and the like... it was also his way of berating the ineffectiveness of 'alternative medicines' out there today; "We looked to natural remedies , finding the things that worked and adopting them as medicines ... everything else is just pot-pourri and soup!"🤣
As Tim Minchin once said, "Do you know what they call alternative medicine that's been proved to work? .... Medicine."
@@IceMetalPunk YES! But I don't think he originated that phrase.
alternative medicine is quite useful but not when "normal" medicine is a requirement
@@rickkwitkoski1976 I first heard it as part of his 9-minute poem "Storm", so while I'm sure the sentiment is older than that, I do think that particular phrasing is his.
@@md4luckycharms It's useful only as a placebo at best, but can also be dangerous.
Our school had a speaker give a seminar on digitoxin biosynthesis a few months ago. If I remember correctly, plants have evolved the ability to produce these types of molecules (cardiac glycosides) several times independently.
I sure love old technology artifacts, use to work as a Biomedical technician in a Hospital and part of the work was supporting the Laboratory department. They had a storeroom containing lots of obsolete laboratory equipment, most of it very old and another room had lots of chemistry containers as at one time the lab technicians use to mix up reagents as part of running tests on patient fluid samples. Anyway one day I was exploring the old storeroom and looking at the chemical bottles and noticed a large glass bottle containing Picric acid which had somewhat dried out over years of storage. Picric acid of course was once used as an explosive however it can be unstable and dangerous, end of story was the lab and surrounding area was evacuated and a bomb disposal team was summoned to attend and remove the Picric acid and destroy it at a gun range, apparently went off with a decent explosion! Sadly a few years ago the old laboratory equipment was removed and destroyed and the old laboratory building was pulled down to make room for a multi level car park.
More in-depth human biochemistry every now and then would be nice.
Well... if you understand the pharmacokinetics of the molecules then you should contribute! I am quite curious honestly, but this is way out of my wheelhouse. I am more a solid state chemistry kinda guy myself...
I agree! More Rob! That was great, even though I understood little more than the mechanics. _"That bit can spin around"_ Yeah this stuff is easy!
Like any language the more i hear the more i'll understand. Keep it coming.
I loved Rob's I know what I know relaxed discussion of what he knows.
I've been watching Periodic Videos since 08.
Man I'm so glad when a new video comes on!
Loved this, it's saturated with so much information
Metformin comes from a plant, lovastatin comes from red yeast, salicylate is from willows. Most of medicinal chemistry gets its ideas from nature, then we synthetically make them better. E.g. So we acetylate the willow extract to get aspirin
I remember making a crude form of aspirin: acetyl salicylic acid in freshman college chemistry class. In medical literature it is often abbreviated ASA.
@@FiveBlackFootedFerrets sounds fun
@@S3v3n13tt3r5 it was great fun! I never lost my love of chemistry and biochemistry.
I was cleaning out a cabinet in a lab and found 2 glass tubes jointed together and held with elastic bands, with what looked like half-melted gold inside. It was around 60 g of cesium, but completely unlabeled. Dealing with that was intersting.
Wonderful video, something in the audio during the initial scene showing the Digitalis sample was absolutely maddening on the ears though. It sounded like there was a high frequency dental drill working right by the microphone.
So in Casino Royale they diagnosed him with tachycardia (fast heart rate) but you mention it causes the heart to pump harder & slower. Is that an inaccuracy on the film's part?
William Withering is a really wizard name!
Especially if was a geriatrician or a neurologist specialising in nerve damage.
He could form a partnership with Dr De'Ath - Withering & De'Ath General Practitioners
Great to see Rob back on
It's fascinating how the various components of the molecule and their spacing and orientations play a part in how the molecule behaves. They're like bumps and grooves on a key
Edit: TIL Digoxin is a steroid
The vast majority of biochemistry boils down to shape and charge. If the charges are in the right place and type (i.e. positive vs negative), and the pieces are in the right shape and orientation, then the molecule will have its specific effect. Change the shape or charges, and the effects change with them. And then of course, the locations of charges also affect the overall shape of the molecule as well, so those are intertwined, too :)
That's exactly right, the lock-and-key comparison is made very often in undergrad biochem. Because almost everything in our body works with enzymes. They are much like locks, folded in complex ways to form active sites where chemical reactions can take place, but only if a molecule (the key) can orient itself into that site in a certain way.
@@At0mix And not only enzymes, either; that's also how receptors work.
Great presentation, thank you!
Wonderful program. Thank you and keep it up.
Another Periodic Video - yes!
This is one of those moments when I am really glad that I spent all those hours in university and medical school, studying bio chemistry! Fascinating and very useful video demonstration, and explanation of the structure with a 3-D model.
In the Casino Royale clip surely it should say bradycardia if it slows the heart rate?
Digoxin poisoning can induce a bidirectional ventricular tachycardia - as well as a range of other arrhythmias. Once you get conduction problems in the circuitry that controls the coordination of the heartbeat, a very wide range of things can happen.
That was my first thought too. Wikipedia has a page on "Digoxin toxicity": it says the heart rate can be too slow or too fast. It's not entirely unusual for an overdose to have the opposite effect of the therapeutic dose. You'd have to ask a cardiologist for why that is... ...I wonder what Rohin of Medlife Crisis would say about Digoxin.
These videos are so amazingly interesting. I’ve been watching them for a long time now and I really want to send my thanks to Riley and the University for making them possible.
Thanks and happy new year
Really refreshing when one hears the words “I don’t know” from a scientist 🧐.
I get this kind of response from my professors a lot, after throwing oddball questions like that at them. I suppose being humble and recognizing what you don't know is always important to be a rigorous scientist.
Great job, Prof. Stockman!
Great episode, loved it! Mr. Stockman seems to really know his stuff, fascinating!
Very nice video. My entire master's research and thesis was over the extraction and quantification of cardenolides from milkweed (Asclepias viridis) leaves.
Anyone else notice the "Ohm's Law Pyramid" on the whiteboard? That's an odd thing to find in the Chemistry department.
Yes. I assumed the apparatus drawn underneath used electricity and (perhaps like electrolysis) you would want to know the current to understand the quantitative yield.
I didn't realize that the "digitalis" referenced in "Casino Royale" is also foxglove. They talk about foxglove in "No Time to Die". So it's in Daniel Craig's first and last Bond films.
I learned a lot in one episode!
Thanks for the Info
The assay for powdered digitalis (in its herbal form) until relatively recently was commonly performed by determining how much digitalis it took to put a set of pigeons into cardiac arrest. Luckily there is an HPLC assay for the pure substance now though.
These videos are much more helpful than my uni courses. Just having their physical model of the molecule structure and seeing the rigidity of the ring back bone and the rotation of the feurone ring makes alot more sense of how chemistry works.
Love these molecular videos!!!!!!!!!!
I looked it up and the LD50 of Digitalis is 28.27 mg/kg
Humans are not rats. LD50 for humans is about 0.1 mg/kg
Very interesting. Thanks
How exciting would it to be to go through the archives of chemicals!!!
Love the old bottle with the string tie for the lid.
Happy New Year!
Thank you very much.
The same to you.
Great video.
Id love to see more biochemistry and organic chemistry from this channel. This was cool :D
"Purified digoxin is typically used at daily doses of 0.125 to 0.25 mg"
i've always had an interest in digitalis and how it works - thanks for the explanation ♥
ok, but don't say it that way, some policeman could get interested about you
@@matteofabbris7877 sigh
This man’s knowledge is outstanding. Explains very well and constructive, enjoyed the video!
Obviously doing it off the top of his head, which is why corrections appear beside him. Might have been better to write a script.
@@pattheplanter No, because corrections in a conversation between scientists let our brain process data biochemically very well, while flawless lectures are tiring for us ;)
As made famous by one of my favourite episodes of Columbo!
Glad to see another Columbophile! Great episode. "Uneasy Lies the Crown".
I hadn't heard that digoxin shrinks the heart, but if I had to guess, it's actually from left ventricular hypertrophy.
Heart failure with preserved ejection fraction (HFpEF) is what happens when the left ventricle becomes too muscular, usually from long-standing hypertension. In this case, the heart failure isn't because the heart can't squeeze enough. It's because its too muscular, so even when it relaxes, the muscle takes up the space where the blood that should be filling it would go. The "cup" holding the blood is smaller. It still pushes that through your body, but it's not nearly enough.
That is opposed to Heart failure with reduced ejection fraction (HFrEF). That's when the heart can hold all the blood it wants, but it can't squeeze enough to move it around.
I would guess that the digoxin makes the heart too muscular, which leads to HFpEF.
That being said, we don't really use digoxin anymore. It has a very narrow therapeutic window, and the side effects can be pretty rough.
More importantly, it hasn't been shown to improve mortality.
If it's used at all, it's used for people with heart failure with reduced ejection fraction (HFrEF) but only to treat symptoms.
Source: MD who has been a fan of this channel forever and finally knows what they are talking about.
An alternative explanation might be that it reduces detrimental remodeling in dilated cardiomyopathy by increasing cardiac contractility
Thank you for the story! Happy new year too!
human heart is almost like a petrol engine, when the heart is weakened, it's behaving like its knocking on low octane fuel but with this medication it would increase the octane level of the fuel. the heart would perform with better pumping rhythm
Found it really interesting. Maybe you could do an episode on the basics of molecular shapes and what they are the shapes they are
Quantum mechanics gives all the structure at a glance, that part of it is simple, worth googling.
Very informative video thank you from India 👍👍😍😍
"Elaborate shrubbery"... can't say I've ever heard of that one before, especially when referring to molecular structures :)
A striking and memorable description that blew right into the memory cells 👍.
Well he starts off saying 'all this shi..', so I'm guessing elaborate shrubbery was a quick catch to cover what he was about to say 😉
i really enjoyed this episode. i love the disection of the parts of the steroid molecule and exolaining their function
This was used in an episode of Columbo.
Digitalis is the name for one aspect of the enemy in the video game Creeper World 3, and it has a net-like appearance not unlike the molecular model. Today I learned!
Thanks
thanks
Can you do an episode on warfarin? Pretty sure it's used as both a cardiovascular medicine and as rat poison.
You are right it's a blood thinner. At high doses it prevents blood from clotting at all. So the rodents hemorrhage and die.
It definitely is used in both….. it was discovered in rotten clover that animals were eating and bleeding out
@Robert Mailander isnt the antidote high dose vitamin K. Thats why rat poison doesn't work in pet stores. Because vitamin k is put in the dog and cat food for said reason. Lol
@@ArtDeGuerra Mechanism of action - Warfarin and related vitamin K antagonists (VKAs) block the function of the vitamin K epoxide reductase complex in the liver, leading to depletion of the reduced form of vitamin K that serves as a cofactor for gamma carboxylation of vitamin K-dependent coagulation factors [1]. I copied this text from a reputable website describing the exact mechanism. Once you've ingested warfarin in great quantity your odds for survival are nil. It completely blocks the mechanism for vitamin k as described above. The only way you stand a chance of surviving is if you did not ingest a fatal dose. Your question was valid. I just thought I needed to give you a more comprehensive answer.
@@FiveBlackFootedFerrets The fun part, if you could call it that, is that it was invented and used as a rat poison many years before someone realised that preventing blood clots was actually useful medically as well
Beatiful flowers. I'm a big fan of the digiplexsis (digitalis x isoplexis).
Fascinating!
@6:11 "and not have all this shi- err... umm.... elaborate shrubbery"
My thinking is the digitalis molecule is shaped in such a way so as to bind to certain receptors on specific cells. Interfacing these triggers the desired cellular mechanisms.
YASSSSS MORE OLD TIMEY SAMPLES!
Excellent episode. I would like to know more about what he said concerning the stripping of a morphine molecule. Which parts can you remove? Where can I find out more information about this?
please someone give that guy a new molecule kit, with plenty of parts!
My Cockeral feasted on a foxglove, it became paralysed, I read to infuse it with sodium hydrogen carbonste solution and glucose, I also googled its half life, when it could just walk again and was recovering, it did what a cockeral does and jumped on the back of a hen and nearly passed out again.......The other event we had was when all the chickenns got so pissed on fermenting pear fruit they had to be taken in from blazing sun and given re-hydrate salts.
can you guys make a video explaining how to construct the t-s diagram of water for the first time, or any pure compound
On the subject of ld50, I've been given a megaphone a few years ago, it was from a protest at Porton down for ld50 animal testing, I don't have any info on the protest itself but its a pretty cool thing to own
6-6-6 the chemical of the beast! Cool viddy!
Digoxin is also used in the surgical termination of pregnancy as well.
6:34 "I can't say I know the answer to that"
I wish more people would admit that then what is currently acceptable in society today.
I came here to see the new video.
I left here with a little bit of my faith in science restored.
idk what kinda scientists, you're talking about, but i'm sorry to hear that that affected your faith in science. Being humble is essential, understanding what it is, that you don't know is really important.
Throwing oddball questions like this at my professors, gets me this kind of a response A LOT and sometimes a week later, there'd be a little chat about anything you found.
I'd have liked to have seen an NMR of the sample, it would be interesting to see if it was still pure, can't believe it is.
It definitely isn't, the vial was clouded and it obviously had not been kept in a controlled climate. There was visible polymerization of the interior, from vapour forming. Cleaning it up would be... possible, but not simple.
It may not have been pure to start with, it may have been a crude extract of the foxglove. So, a mixture of the various steroid compounds found in the leaf. I would love to see an assay of the activity as well as an analysis of the compounds present. I think digoxin is pretty stable. Modern digoxin tablets have a three year shelf-life.
Please give a room tour of the professor, I would really like it
A bit unsettling that you find stuff like this
How funny to see that bottle. My first job as a chemist was at Lannett.
What does the foxglove do with digitalis? It can't be intended to strengthen the heart muscle, in a plant which has no heart.
It kills animals that enjoys eating foxgloves. This tends towards better survival.
I’d like to see a video that includes a synthesis, a simple one, one or two steps, along with appropriate analysis of the starting and end products to show what has been accomplished.
1:37 One thing in organic chemistry that always puzzled me is how the scientists came up with these spatial molecule models. Alright, simple substances like ethanol or acetone should be easy. But this one has 42 carbon atoms - how in the world did they arrange it the way they did, and how did they prove that it's correct?
So how exactly did he figure out the doseage?
take care with the stuff
There's some really high pitched noise at the beginning of the video.
I take this!
This is interesting like how did they know back then, that what they were making is a medicine that is still used today?
Guess and die!
Nitro-glicerene is also used for some heart issues. Just don't jump up and down after taking the tablets.
why does the hydroxyl make it long-lasting in the body?
Potion seller, my heart is going into battle, and I need only your strongest potions.
I wish I learn all these in high school.
The ringing noises throughout the first minute were painful
Hello professors
Lots of medicines and poisons have that steroidal structure. Seems likely that it is because it can bind to cell walls and then do things to ion channels.
A lot of common human steroids actually have that structure specifically so they *don't* interact with cell walls - steroid hormones for instance diffuse straight through cell walls and interact with receptors inside of cells, whereas other types of hormones need to interact with cell surface receptors
If you had an enlarged heart would this be a valid treatment?
if you've got one[i do] i'll give you my daily pill regiment .
my EF went from 22% to 51%
let me know and i'll take the time.
new video!
Anyone else worried he was going to drop it?
Yes, me. His erratic movements made me nervous.
I remember the name of the toxin from an episode of The X-Files. I think it was the Eve 6 episode.
What does it smell like?
Despite having watched Casino Royale not less than 3 times, I didn't realize Bond was poisoned by digitalis until now XD
Ssssso, reviewing this new knowledge, a wrong dose is a right dose, but only if you are a Bond villain. Thank you 👍