Hi, welcome back to the Internet Book of Critical Care Podcast. I'm here with Adam Thomas,

and we're going to talk about Valproc acid intoxication to distract everyone from the political

Twitter. Yeah, Hanner Key, but this one will be a fun distraction, Josh, because it's a quick

hit, but the physiology is really interesting,

right? These are really interesting overdoses. Let's get straight into the pharmacology and pathophysiology

of philproc acid intoxication. So tell me about first off, when we talk about restratification,

dosing, why is it important to figure out formulations and absorption and timing. Yeah, so pharmacokinetics is super

important in toxicology. And this is particularly important for patients who took sustained

release or extended release valproc acid. So these patients can show up. They may have a normal

valproc acid level initially. And then their levels can gradually increase over a period up to

about 24 hours. So this can essentially cause what is known

as like the so-called toxin bomb where patients look fine initially. They're triaged, you know,

to the floor or their sent home, and then they kind of fall apart. Agreed. And this is maybe that

patient that our colleagues saw and emerge. They were medically cleared, went to psych, and then

were being called for either a code blue or a console because they're really not doing so well over in psych. Exactly. Let's move on to protein binding and

distribution in the same light. Is this drug, because this is important for our clearance discussion,

is it small, is it big? Is it protein bound? I.e., can I dialize this drug or not, Josh? Yeah, so it's

relatively small, essentially fatty acid type of molecule.

And at therapeutic doses, it's protein bound.

But then at toxic levels, over about 150mg per ML or 1,000 micromoles per liter, it's

increasingly free.

So essentially, the drug saturates all of the protein binding sites and the amount of free

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