WEBVTT 00:00:06.059 --> 00:00:09.800 Welcome to the bed. We'll go ahead and give you 00:00:09.800 --> 00:00:12.580 the story. This is all going to happen super 00:00:12.580 --> 00:00:40.289 fast. Welcome to the emergency room. Welcome 00:00:40.289 --> 00:00:49.899 back to the Deep Dive. Today we are walking into 00:00:49.899 --> 00:00:52.460 what I think is one of the most high pressure 00:00:52.460 --> 00:00:55.700 environments in medicine. Imagine you are standing 00:00:55.700 --> 00:01:00.039 in a pediatric emergency room or a neurology 00:01:00.039 --> 00:01:05.340 ward. A child is having a seizure. It is chaotic, 00:01:05.560 --> 00:01:08.099 the parents are absolutely terrified, and the 00:01:08.099 --> 00:01:11.560 clock is ticking. It is. And in that moment, 00:01:11.859 --> 00:01:14.400 the medication you pull, how you mix it, how 00:01:14.400 --> 00:01:18.290 fast you push it, That determines not just if 00:01:18.290 --> 00:01:21.370 the seizure stops, but if that child wakes up 00:01:21.370 --> 00:01:23.769 safely. It's the ultimate test of preparation. 00:01:23.930 --> 00:01:26.150 I mean, you can't be looking up the pharmacokinetics 00:01:26.150 --> 00:01:28.790 of Finnytoin while a child is actively seizing 00:01:28.790 --> 00:01:30.569 in front of you. You have to know it. You have 00:01:30.569 --> 00:01:32.870 to know it in your bones. And that is our mission 00:01:32.870 --> 00:01:36.310 today. We are stepping into the shoes of a pediatric 00:01:36.310 --> 00:01:40.359 neurology and nursing educator and... and NCLEX 00:01:40.359 --> 00:01:43.560 coach. We've got a massive stack of monographs, 00:01:43.760 --> 00:01:45.959 clinical guidelines, safety protocols right here 00:01:45.959 --> 00:01:47.920 on the table. We do. But we aren't just going 00:01:47.920 --> 00:01:50.079 to be reading drug labels. We're going to deconstruct 00:01:50.079 --> 00:01:52.359 the why behind the what. Which is, I mean, it's 00:01:52.359 --> 00:01:53.959 the only way to actually remember this stuff. 00:01:53.959 --> 00:01:56.260 Right. If you just memorize phenytoin causes 00:01:56.260 --> 00:01:59.219 gum overgrowth, you are going to forget it the 00:01:59.219 --> 00:02:01.859 day after the exam. Of course. But if you understand 00:02:01.859 --> 00:02:03.640 the mechanism, if you understand the physiology, 00:02:04.219 --> 00:02:06.250 it sticks with you. We're really focusing on 00:02:06.250 --> 00:02:09.090 the Pareto principle here, the 80 -20 rule. There 00:02:09.090 --> 00:02:12.169 are, what, dozens of anti -epileptic drugs or 00:02:12.169 --> 00:02:14.509 AEDs? Though many. But we are focusing on that 00:02:14.509 --> 00:02:17.430 core group that drives, you know, 80 % of the 00:02:17.430 --> 00:02:20.569 clinical decisions and arguably 99 % of the safety 00:02:20.569 --> 00:02:23.250 risks. These are the heavy hitters. We're talking 00:02:23.250 --> 00:02:25.610 about drugs that manage electricity in the brain. 00:02:26.050 --> 00:02:29.270 They're powerful. They're often toxic. And in 00:02:29.270 --> 00:02:32.669 pediatrics, the margin for error is it's razor 00:02:32.669 --> 00:02:35.560 thin. Why is that? Why pediatrics specifically? 00:02:35.699 --> 00:02:37.780 Well, a developing brain just doesn't react like 00:02:37.780 --> 00:02:40.360 an adult brain. Yeah. A toddler's liver doesn't 00:02:40.360 --> 00:02:42.460 metabolize like an adult's liver. Everything 00:02:42.460 --> 00:02:44.419 is different. Everything is weight -based. Got 00:02:44.419 --> 00:02:47.199 it. So we have a lineup to get through. Finitoin, 00:02:47.439 --> 00:02:49.979 carbamazepine, phenobarbital, valproic acid, 00:02:50.199 --> 00:02:53.580 toparamate, gabapentin, and leviteracetam. A 00:02:53.580 --> 00:02:55.379 lot to cover. And plus we have to talk about 00:02:55.379 --> 00:02:58.840 the rescue meds and the specific treatments for 00:02:58.840 --> 00:03:01.300 absence seizures. Right. It sounds like a lot, 00:03:01.360 --> 00:03:03.240 but there is a narrative arc here. We're gonna 00:03:03.240 --> 00:03:06.020 move from the older, I'd say junior drugs, the 00:03:06.020 --> 00:03:08.240 ones that work really well, but require intense 00:03:08.240 --> 00:03:10.699 monitoring, to the newer generation that solves 00:03:10.699 --> 00:03:13.000 some of those problems, but introduces entirely 00:03:13.000 --> 00:03:14.360 new ones. All right, so let's start with that 00:03:14.360 --> 00:03:16.840 high -maintenance group, the sodium channel blockers. 00:03:17.159 --> 00:03:19.500 And I feel like we have to start with the beast 00:03:19.500 --> 00:03:24.469 itself. Finny Toyne. Commonly known as Dilantin. 00:03:25.550 --> 00:03:27.909 Yes. Finitoin is the grandfather of the unit. 00:03:28.569 --> 00:03:31.569 It's a hydantoin anticonvulsant. It has been 00:03:31.569 --> 00:03:34.009 around for decades, and despite all the shiny 00:03:34.009 --> 00:03:37.469 new drugs we have, it is still a workhorse for 00:03:37.469 --> 00:03:40.560 tonic -clonic seizures. and for status epilepticus. 00:03:41.120 --> 00:03:43.500 But it demands respect. OK, let's get into the 00:03:43.500 --> 00:03:46.400 mechanism first. It blocks sodium channels. Now, 00:03:46.479 --> 00:03:48.580 to me, that sounds a little abstract. What is 00:03:48.580 --> 00:03:50.599 it actually doing to the neuron? OK, so think 00:03:50.599 --> 00:03:53.360 about a seizure as a wildfire. OK. For a fire 00:03:53.360 --> 00:03:56.300 to spread, it needs to jump from tree to tree. 00:03:56.620 --> 00:03:59.879 In the brain, for a seizure to generalize, that 00:03:59.879 --> 00:04:02.180 electrical impulse has to propagate from neuron 00:04:02.180 --> 00:04:05.810 to neuron. Finitoin acts like a fire break. It 00:04:05.810 --> 00:04:08.530 blocks those voltage -sensitive sodium channels, 00:04:09.169 --> 00:04:11.590 specifically in the neurons that are firing way 00:04:11.590 --> 00:04:13.810 too rapidly. So it doesn't necessarily stop the 00:04:13.810 --> 00:04:16.550 spark from happening? No. But it prevents that 00:04:16.550 --> 00:04:18.250 spark from spreading across the whole forest? 00:04:18.470 --> 00:04:20.870 Precisely. It limits the propagation of the seizure 00:04:20.870 --> 00:04:23.709 activity. It puts a damper on the ability of 00:04:23.709 --> 00:04:26.050 that neuron to reset and fire again instantly. 00:04:26.769 --> 00:04:28.810 It basically forces a little time out on the 00:04:28.810 --> 00:04:31.410 sodium channel. That sounds great on paper, but 00:04:31.410 --> 00:04:33.670 the pharmacology of this drug is where it starts 00:04:33.670 --> 00:04:36.949 to get, well, frankly, terrifying. I'm looking 00:04:36.949 --> 00:04:39.490 at the phrase zero -order kinetics. Most drugs 00:04:39.490 --> 00:04:41.750 don't work this way, do they? No, not at all. 00:04:41.889 --> 00:04:44.209 Most drugs follow first -order kinetics. That's 00:04:44.209 --> 00:04:46.300 linear. Meaning? Meaning if you have a headache 00:04:46.300 --> 00:04:48.980 and you take 200 milligrams of ibuprofen and 00:04:48.980 --> 00:04:51.399 then later you take 400, you get roughly double 00:04:51.399 --> 00:04:54.139 the blood level. The liver can handle the load, 00:04:54.519 --> 00:04:57.180 so the output matches the input. But phenytoin. 00:04:57.339 --> 00:05:00.500 Phenytoin breaks that rule. Completely. Phenytoin 00:05:00.500 --> 00:05:03.220 follows something called Michaelis -Menten kinetics, 00:05:03.500 --> 00:05:06.660 or what we call zero -order kinetics. Okay. Imagine 00:05:06.660 --> 00:05:09.279 a supermarket checkout line. If five people are 00:05:09.279 --> 00:05:11.139 in line, the cashier handles them just fine. 00:05:11.500 --> 00:05:13.379 If 10 people come, they still handle them fine. 00:05:13.779 --> 00:05:16.600 But eventually, that cashier is working at their 00:05:16.600 --> 00:05:20.139 absolute maximum speed. They physically cannot 00:05:20.139 --> 00:05:22.839 scan items any faster. I see where this is going. 00:05:23.040 --> 00:05:27.160 That cashier is the liver enzyme, CYP2C9, trying 00:05:27.160 --> 00:05:30.009 to metabolize phenytoin. So once the liver enzyme 00:05:30.009 --> 00:05:32.569 is saturated, once that cashier is maxed out, 00:05:32.970 --> 00:05:35.009 what happens if you add just a little bit more 00:05:35.009 --> 00:05:37.829 drug into the line? Chaos. Absolute chaos. Because 00:05:37.829 --> 00:05:40.750 the checkout line is full. Any new drug you add 00:05:40.750 --> 00:05:43.329 has nowhere to go. So it just backs up. It piles 00:05:43.329 --> 00:05:45.670 up in the bloodstream immediately. So a very, 00:05:45.670 --> 00:05:48.779 very small increase in... dose, I'm talking a 00:05:48.779 --> 00:05:51.459 tiny adjustment, can cause the serum level to 00:05:51.459 --> 00:05:54.160 skyrocket from therapeutic straight into toxic. 00:05:54.319 --> 00:05:56.600 And that explains why the therapeutic window 00:05:56.600 --> 00:05:58.779 is so incredibly narrow. You're balancing on 00:05:58.779 --> 00:06:01.079 a knife's edge. You are. And that's why we draw 00:06:01.079 --> 00:06:03.660 blood levels so frequently. You can't just guess 00:06:03.660 --> 00:06:05.899 with phenytoin. You have to know exactly where 00:06:05.899 --> 00:06:08.259 you are on that saturation curve. OK, now let's 00:06:08.259 --> 00:06:10.399 move to administration. This is the stuff that 00:06:10.399 --> 00:06:13.060 I think keeps nurses up at night. The the purple 00:06:13.060 --> 00:06:16.100 glove warning. This is a classic war story scenario. 00:06:16.100 --> 00:06:20.240 Right. Finitoin is inherently alkaline. It is 00:06:20.240 --> 00:06:23.459 incredibly irritating to veins. So if you are 00:06:23.459 --> 00:06:27.300 pushing IV Finitoin and that 5E line infiltrates. 00:06:27.620 --> 00:06:29.379 Meaning the needle slips out of the vein and 00:06:29.379 --> 00:06:31.319 the drug goes into the tissue. Exactly. When 00:06:31.319 --> 00:06:33.800 it goes into the tissue, it destroys it. And 00:06:33.800 --> 00:06:35.420 we're not talking about just a little redness. 00:06:35.439 --> 00:06:37.860 Oh, this is necrosis. The hand swells up, it 00:06:37.860 --> 00:06:40.879 turns purple, and the tissue dies. It's literally 00:06:40.879 --> 00:06:43.120 called purple glove syndrome. And in severe cases, 00:06:43.160 --> 00:06:46.500 it can lead to amputation. Wow. Okay, so to avoid 00:06:46.500 --> 00:06:49.540 that, there are very strict speed limits on how 00:06:49.540 --> 00:06:52.040 fast you can push it. Speed kills with phenytoin. 00:06:52.100 --> 00:06:54.839 Really does. For two reasons. One is the tissue 00:06:54.839 --> 00:06:57.339 irritation we just talked about. But the bigger, 00:06:57.379 --> 00:07:01.300 more immediate risk is the heart. Phenytoin and 00:07:01.300 --> 00:07:04.139 the propylene glycol it's mixed in is a cardiac 00:07:04.139 --> 00:07:08.160 depressant. You slam it in. You will cause profound 00:07:08.160 --> 00:07:11.680 hypotension and arrhythmias, bradycardia, heart 00:07:11.680 --> 00:07:14.970 block, even V -fib. So what is the speed limit? 00:07:15.170 --> 00:07:17.930 How slow are we talking? For an adult, you never 00:07:17.930 --> 00:07:21.449 exceed 50 milligrams per minute, ever. But for 00:07:21.449 --> 00:07:24.850 a child, much, much slower. We are talking one 00:07:24.850 --> 00:07:27.069 to three milligrams per kilogram per minute. 00:07:27.069 --> 00:07:29.750 OK. And you are staring at that cardiac monitor 00:07:29.750 --> 00:07:32.889 the entire time. No distractions. And because 00:07:32.889 --> 00:07:35.970 of these risks, the Purple Glove, the cardiac 00:07:35.970 --> 00:07:38.230 collapse hospitals have started using a different 00:07:38.230 --> 00:07:41.129 version of the drug, right? Phosphonitoin? Yes. 00:07:41.269 --> 00:07:43.730 The brand name is Cerebix. Phosphonitoin is a 00:07:43.730 --> 00:07:45.930 pro drug. Break that down for us. What exactly 00:07:45.930 --> 00:07:48.610 is a pro drug? It means that phosphonitoin itself 00:07:48.610 --> 00:07:51.089 is inactive. It's not an anticonvulsant yet. 00:07:51.110 --> 00:07:53.730 OK. It's water -soluble and much, much friendlier 00:07:53.730 --> 00:07:56.259 to the veins. Yeah. You inject it. And it travels 00:07:56.259 --> 00:07:58.279 to the liver, or the red blood cells, where the 00:07:58.279 --> 00:08:01.060 body cleaves off a phosphate group. Once that 00:08:01.060 --> 00:08:03.139 happens, it becomes phenytoin. So it's like a 00:08:03.139 --> 00:08:05.319 Trojan horse. It goes in nice and smooth, and 00:08:05.319 --> 00:08:07.300 then it transforms into the active drug once 00:08:07.300 --> 00:08:09.500 it's safely inside the body. That's a perfect 00:08:09.500 --> 00:08:12.920 analogy. It drastically reduces the risk of purple 00:08:12.920 --> 00:08:15.560 glove syndrome because it's not caustic to the 00:08:15.560 --> 00:08:20.240 tissue. But, and this is a huge but for the boards 00:08:20.240 --> 00:08:23.639 and for practice, it does not eliminate the cardiac 00:08:23.639 --> 00:08:26.740 risk. Once it converts to phenytoin, you still 00:08:26.740 --> 00:08:29.800 have the exact same cardiac effects. So you still 00:08:29.800 --> 00:08:31.800 have to monitor the heart rate and blood pressure 00:08:31.800 --> 00:08:34.539 just as closely, even with the safer version. 00:08:34.740 --> 00:08:36.779 That is a critical distinction. Just because 00:08:36.779 --> 00:08:38.940 it's safer on the vein doesn't mean it's safer 00:08:38.940 --> 00:08:41.440 on the heart. Not at all. Now let's talk about 00:08:41.440 --> 00:08:44.200 the side effects that happen over months or years. 00:08:44.720 --> 00:08:46.879 The patient isn't actively seizing, but they're 00:08:46.879 --> 00:08:50.159 dealing with some... Pretty strange changes to 00:08:50.159 --> 00:08:53.019 their body. Yes, the exam favorites. First up 00:08:53.019 --> 00:08:56.059 is gingival hyperplasia. The gums growing over 00:08:56.059 --> 00:08:58.379 the teeth. It's startling to see, really. The 00:08:58.379 --> 00:09:01.299 gum tissue becomes fibrotic and enlarged. I mean, 00:09:01.399 --> 00:09:03.539 it can literally bury the teeth. And for a child, 00:09:03.559 --> 00:09:06.100 that's a huge deal. It's a hygiene nightmare 00:09:06.100 --> 00:09:09.259 and a major social issue. We have to teach meticulous, 00:09:09.460 --> 00:09:12.320 oral, caresoft, brushing, flossing, frequent 00:09:12.320 --> 00:09:15.059 dental cleanings. That can minimize the growth. 00:09:15.279 --> 00:09:17.200 But sometimes surgery is needed just to trim 00:09:17.200 --> 00:09:20.519 the gums back. And then there's the hair, her 00:09:20.519 --> 00:09:22.919 suitism. Excessive hair growth on the face and 00:09:22.919 --> 00:09:25.360 body. Now imagine you are a 14 -year -old girl. 00:09:25.460 --> 00:09:27.759 Right. You already have epilepsy, which can be 00:09:27.759 --> 00:09:30.320 isolating. And now your medication is causing 00:09:30.320 --> 00:09:33.120 you to grow mustache and thick arm hair. The 00:09:33.120 --> 00:09:35.500 non -compliance risk there must be massive. It 00:09:35.500 --> 00:09:37.879 is the number one reason for non -adherence in 00:09:37.879 --> 00:09:39.519 that demographic. Right. I mean, they would rather 00:09:39.519 --> 00:09:41.779 risk a seizure than deal with the body image 00:09:41.779 --> 00:09:43.799 issues. And you have to be sensitive to that. 00:09:43.820 --> 00:09:45.940 You have to talk about it. And lastly, the bones. 00:09:46.340 --> 00:09:49.360 Right. Phenytoin induces liver enzymes that chew 00:09:49.360 --> 00:09:52.740 up vitamin D. OK. Over time, this leads to weak 00:09:52.740 --> 00:09:55.779 bones, osteomalacia, or even rickets in kids. 00:09:56.159 --> 00:09:58.659 So these patients need vitamin D and calcium 00:09:58.659 --> 00:10:00.899 supplements if they are on it long -term. Okay, 00:10:00.960 --> 00:10:03.519 so that is phenytoin. The high -maintenance, 00:10:03.799 --> 00:10:06.519 zero -order, gum -growing fire break? Let's pivot 00:10:06.519 --> 00:10:10.620 to its cousin, carbamazepine or tigretil. Carbamazepine 00:10:10.620 --> 00:10:14.240 is chemically related to the tricyclic antidepressants, 00:10:14.240 --> 00:10:16.620 actually. Really? Yeah, it's a carboxymide. We 00:10:16.620 --> 00:10:19.279 use it for vocal seizures and generalized tonic 00:10:19.279 --> 00:10:22.529 -clonic seizures. But it also has this second 00:10:22.529 --> 00:10:25.110 life as a mood stabilizer for bipolar disorder 00:10:25.110 --> 00:10:28.769 and for neuropathic pain. The mechanism is similar 00:10:28.769 --> 00:10:30.990 to phenytoin. It's blocking sodium channels, 00:10:31.549 --> 00:10:34.409 but it has this kinetic trick that is entirely 00:10:34.409 --> 00:10:37.250 unique, this idea of auto -induction. This is 00:10:37.250 --> 00:10:39.210 fascinating, pharmacologically. We talked about 00:10:39.210 --> 00:10:41.809 how phenytoin saturates the liver enzymes. Right, 00:10:42.049 --> 00:10:44.529 it maxes them out. Carbon mesopine does the exact 00:10:44.529 --> 00:10:47.600 opposite. It trains the liver to be a hyper -efficient 00:10:47.600 --> 00:10:49.840 machine. Like it's sending the liver to the gym. 00:10:50.059 --> 00:10:53.279 Exactly. It induces the CYP3A4 enzyme, which 00:10:53.279 --> 00:10:55.539 is the very enzyme responsible for metabolizing 00:10:55.539 --> 00:10:58.080 carbamazepine. So the drug actually tells the 00:10:58.080 --> 00:11:00.779 liver, build more machinery to destroy me. So 00:11:00.779 --> 00:11:02.539 you start the patient on a dose and it works 00:11:02.539 --> 00:11:05.320 great, but then two weeks later. The levels drop. 00:11:05.620 --> 00:11:07.820 Not because you changed the dose, but because 00:11:07.820 --> 00:11:10.019 the liver has bulked up and is now chewing through 00:11:10.019 --> 00:11:12.960 the drug twice as fast. The half -life can drop 00:11:12.960 --> 00:11:16.470 from, say, 30 hours, down to 15 hours in the 00:11:16.470 --> 00:11:18.929 first few weeks of therapy. So clinically, you 00:11:18.929 --> 00:11:20.870 have to anticipate this. You can't be caught 00:11:20.870 --> 00:11:23.049 off guard. You have to warn the parents. You 00:11:23.049 --> 00:11:25.210 say, look, we might need to increase the dose 00:11:25.210 --> 00:11:27.610 in a month, not because the epilepsy is getting 00:11:27.610 --> 00:11:29.929 worse, but because the body is getting too efficient 00:11:29.929 --> 00:11:32.789 at clearing the drug. OK, now, we need to start 00:11:32.789 --> 00:11:35.049 for a really serious safety warning. The black 00:11:35.049 --> 00:11:38.029 box warning regarding genetics. The HLAB Star 00:11:38.029 --> 00:11:41.169 1502 allele. This is a matter of life and death, 00:11:41.169 --> 00:11:43.309 and it's a real triumph of pharmacogenomics. 00:11:44.030 --> 00:11:46.370 We discovered that patients with this specific 00:11:46.370 --> 00:11:50.330 genetic marker, the HLA -B star 1502 allele, 00:11:50.570 --> 00:11:53.710 have a massive catastrophic immune reaction to 00:11:53.710 --> 00:11:55.929 carbamazepine. And who carries this genetic marker? 00:11:56.129 --> 00:11:58.169 It is most prevalent in people of Asian ancestry, 00:11:58.649 --> 00:12:00.570 particularly Han, Chinese, Thai, and Malaysian 00:12:00.570 --> 00:12:02.570 populations. And if they have this marker and 00:12:02.570 --> 00:12:04.610 they take the drug? Sidney Johnson syndrome, 00:12:04.909 --> 00:12:07.590 SJS, or toxic epidermal necrolysis tendonitis. 00:12:07.679 --> 00:12:09.980 We hear those terms a lot in nursing school, 00:12:10.440 --> 00:12:12.759 but describe what that actually looks like for 00:12:12.759 --> 00:12:15.019 a nurse on the floor. What are you seeing? It's 00:12:15.019 --> 00:12:18.139 horrific. I mean, it is essentially a burn from 00:12:18.139 --> 00:12:20.720 the inside out. The immune system attacks the 00:12:20.720 --> 00:12:23.899 skin and the mucous membranes. The patient blisters 00:12:23.899 --> 00:12:26.620 and not just on their arm, but inside their mouth, 00:12:26.879 --> 00:12:30.419 their eyes. They're urethra. Wow. The skin slows 00:12:30.419 --> 00:12:34.000 off in sheets. The mortality rate is high, mostly 00:12:34.000 --> 00:12:36.240 due to infection and massive fluid loss. Well, 00:12:36.299 --> 00:12:38.399 the protocol isn't just watch for a rash. It's 00:12:38.399 --> 00:12:41.000 much more proactive. Oh, absolutely. The protocol 00:12:41.000 --> 00:12:43.629 is... If you have a patient of Asian descent, 00:12:44.029 --> 00:12:45.889 you must screen for this allele before you write 00:12:45.889 --> 00:12:47.590 the first prescription. Before they even take 00:12:47.590 --> 00:12:50.129 one dose. Before one dose. If they are positive, 00:12:50.509 --> 00:12:52.389 carbamazepine is absolutely contraindicated. 00:12:52.590 --> 00:12:55.230 You do not pass go. You find another drug. Are 00:12:55.230 --> 00:12:57.210 there other blood -related warnings with this 00:12:57.210 --> 00:13:00.200 one? Yes. Carbamazepine can suppress the bone 00:13:00.200 --> 00:13:03.340 marrow. It can cause leukopenia, which is low 00:13:03.340 --> 00:13:06.019 white blood cells, anemia, and thrombocytopenia, 00:13:06.159 --> 00:13:08.399 low platelets. So if a mom calls the clinic and 00:13:08.399 --> 00:13:11.320 says, my kid on tigretto has a sore throat and 00:13:11.320 --> 00:13:14.320 a fever that just won't go away, or he's covered 00:13:14.320 --> 00:13:17.210 in new bruises. That is a red alert. That is 00:13:17.210 --> 00:13:20.110 not something you watch. You need a CBC immediately 00:13:20.110 --> 00:13:22.629 to make sure he isn't developing a plastic anemia 00:13:22.629 --> 00:13:25.669 or a granulocytosis. There's one more nuance 00:13:25.669 --> 00:13:28.710 about carbamazepine administration. The liquid 00:13:28.710 --> 00:13:31.769 versus the tablet. The notes say they aren't 00:13:31.769 --> 00:13:34.370 bioequivalent. Yeah, this trips people up all 00:13:34.370 --> 00:13:37.409 the time. The suspension is absorbed much, much 00:13:37.409 --> 00:13:40.409 faster than the tablet. It creates a higher peak 00:13:40.409 --> 00:13:42.830 level in the blood. So if you take a kid who 00:13:42.830 --> 00:13:45.250 is stable on tablets you switch them to the same 00:13:45.250 --> 00:13:47.429 number of milligrams and liquid Maybe they have 00:13:47.429 --> 00:13:50.009 a sore throat and can't swallow pills You might 00:13:50.009 --> 00:13:52.269 accidentally cause toxicity just because it hits 00:13:52.269 --> 00:13:54.210 the system so fast. So what do you do? You have 00:13:54.210 --> 00:13:56.450 to space it out, right? You give smaller doses 00:13:56.450 --> 00:13:59.600 more frequently instead of giving it BID Twice 00:13:59.600 --> 00:14:02.419 a day, you might have to switch to QID four times 00:14:02.419 --> 00:14:04.840 a day, just to flatten out that absorption curve 00:14:04.840 --> 00:14:07.500 and avoid those toxic peaks. OK, let's shift 00:14:07.500 --> 00:14:09.740 gears. We're leaving the sodium channel blockers, 00:14:09.840 --> 00:14:11.919 and we're going back in time to the old guard. 00:14:12.139 --> 00:14:15.559 Yeah. The barbiturates, specifically phenobarbital. 00:14:15.980 --> 00:14:18.320 This is likely the oldest drug we will discuss 00:14:18.320 --> 00:14:21.299 today. It was introduced in 1912. Wow. The fact 00:14:21.299 --> 00:14:24.399 that we still use it. tells you two things, how 00:14:24.399 --> 00:14:27.059 effective it is, but also how limited our options 00:14:27.059 --> 00:14:29.200 were for a very long time. And this one works 00:14:29.200 --> 00:14:33.080 on GABA. The brain's brake pedal, gamma -aminobutyric 00:14:33.080 --> 00:14:36.340 acid. When GABA binds to its receptor, it opens 00:14:36.340 --> 00:14:39.000 a chloride channel. Chloride, a negative ion, 00:14:39.200 --> 00:14:41.440 rushes in, makes the cell more negative, and 00:14:41.440 --> 00:14:44.070 basically tells the neuron, Do not fire. Now 00:14:44.070 --> 00:14:45.970 benzodiazepines also do this. We'll talk about 00:14:45.970 --> 00:14:49.029 them later. What is the difference between how, 00:14:49.029 --> 00:14:52.070 say, Valium works and how phenobarbital works? 00:14:52.190 --> 00:14:54.029 It's the difference between how often and how 00:14:54.029 --> 00:14:56.929 long. OK. Benzodiazepines increase the frequency 00:14:56.929 --> 00:14:58.870 of the chloride channel opening. They make the 00:14:58.870 --> 00:15:02.059 door flap open and closed really rapidly. Phenobarbital 00:15:02.059 --> 00:15:04.559 increases the duration, it props the door wide 00:15:04.559 --> 00:15:06.419 open, and holds it there. That sounds like a 00:15:06.419 --> 00:15:09.120 much more forceful, much heavier break. It is, 00:15:09.200 --> 00:15:11.799 which is exactly why it is so sedating. It essentially 00:15:11.799 --> 00:15:15.059 puts the brain to sleep, and in high doses, it 00:15:15.059 --> 00:15:17.460 puts the respiratory drive to sleep too. That's 00:15:17.460 --> 00:15:20.580 the major risk. And yet, in pediatrics, we sometimes 00:15:20.580 --> 00:15:23.840 see the exact opposite of sleep, the pediatric 00:15:23.840 --> 00:15:26.659 paradox. This is a classic pediatric nursing 00:15:26.659 --> 00:15:30.769 phenomenon. You give a child phenobarbital, expecting 00:15:30.769 --> 00:15:35.179 them to be calm and sedated. they become a tornado. 00:15:35.259 --> 00:15:38.559 Chuckles. A tornado. Hyperactive, irritable, 00:15:38.799 --> 00:15:41.220 aggressive, literally banking off the walls. 00:15:41.259 --> 00:15:43.600 That has to be so confusing for parents. It's 00:15:43.600 --> 00:15:45.419 incredibly distressing. They think the epilepsy 00:15:45.419 --> 00:15:47.419 is affecting the behavior or that their child 00:15:47.419 --> 00:15:50.059 is just being bad. No, it's the drug. It disinhibits 00:15:50.059 --> 00:15:52.200 them. And if that happens, we usually have to 00:15:52.200 --> 00:15:53.899 switch medications because it just interferes 00:15:53.899 --> 00:15:56.080 with learning and development too much. So why 00:15:56.080 --> 00:15:58.799 do we still use it if it's so sedating and has 00:15:58.799 --> 00:16:03.179 this major behavioral risk? Two words. The NICU. 00:16:04.000 --> 00:16:06.440 Neonatal seizures are very, very difficult to 00:16:06.440 --> 00:16:08.860 treat. And phenobarbital is still the gold standard, 00:16:08.960 --> 00:16:11.639 the first -line therapy for newborns. Their brains 00:16:11.639 --> 00:16:13.779 just respond to it better than older children. 00:16:14.220 --> 00:16:16.700 Plus, it has a wondrously long half -life. So 00:16:16.700 --> 00:16:18.960 you can dose it just once a day. Right. Which 00:16:18.960 --> 00:16:20.840 is great for maintenance therapy if the side 00:16:20.840 --> 00:16:22.879 effects are tolerated. But just like phenytoin, 00:16:22.960 --> 00:16:26.240 it's an enzyme inducer. Yes. It eats up other 00:16:26.240 --> 00:16:30.389 drugs. If you're on phenobarbital and, say, warfarin 00:16:30.389 --> 00:16:33.129 or hormonal contraceptives. The phenobarbital 00:16:33.129 --> 00:16:35.470 will make those other drugs less effective. It's 00:16:35.470 --> 00:16:38.070 a major source of drug interactions. All right, 00:16:38.070 --> 00:16:41.370 let's move to the kitchen sink drug, valprog 00:16:41.370 --> 00:16:45.509 acid or Deepakote. If phenytoin is a sniper rifle 00:16:45.509 --> 00:16:48.049 targeting sodium channels, valprog acid is a 00:16:48.049 --> 00:16:53.340 shotgun or maybe a grenade. Yeah. Laughs. Okay, 00:16:53.340 --> 00:16:55.200 why do you say that? Because we still aren't 00:16:55.200 --> 00:16:57.879 100 % sure of everything it does. We know it 00:16:57.879 --> 00:17:00.179 increases GABA levels by stopping GABA from breaking 00:17:00.179 --> 00:17:02.840 down. We know it blocks sodium channels. We suspect 00:17:02.840 --> 00:17:05.480 it messes with calcium channels. It just, it 00:17:05.480 --> 00:17:07.079 hits everything. Which is what makes it broad 00:17:07.079 --> 00:17:09.180 spectrum. Exactly. It works for almost every 00:17:09.180 --> 00:17:12.420 seizure type generalized focal absence myoclonic. 00:17:12.619 --> 00:17:15.259 It's also a first line mood stabilizer and it's 00:17:15.259 --> 00:17:17.400 used for migraine prevention. It is the Swiss 00:17:17.400 --> 00:17:19.890 army knife of neurology. But, you know, carrying 00:17:19.890 --> 00:17:22.009 a Swiss Army knife in your pocket has risks. 00:17:22.349 --> 00:17:24.509 Valproc acid has some of the scariest black box 00:17:24.509 --> 00:17:26.809 warnings in the book. You call them the big three. 00:17:27.009 --> 00:17:29.230 The big three. Hepatotoxicity, pancreatitis, 00:17:29.369 --> 00:17:31.930 and teratogenicity. Let's take them one by one. 00:17:32.970 --> 00:17:35.130 Hepatotoxicity. This isn't just, oh, the labs 00:17:35.130 --> 00:17:37.450 are a little elevated. No, this is fatal liver 00:17:37.450 --> 00:17:40.029 failure. And the demographic at the absolute 00:17:40.029 --> 00:17:42.859 highest risk... is children under two years old, 00:17:43.240 --> 00:17:45.119 especially those with underlying mitochondrial 00:17:45.119 --> 00:17:47.880 disorders. So in a toddler on this drug, you're 00:17:47.880 --> 00:17:50.420 watching those LFTs, the liver function tests, 00:17:50.680 --> 00:17:53.220 like a hawk. You're watching the labs, and you're 00:17:53.220 --> 00:17:55.740 watching the child clinically. Are they jaundiced? 00:17:55.940 --> 00:17:58.759 Is their urine dark? Are they lethargic? Vomiting? 00:17:58.980 --> 00:18:01.640 Those are all signs the liver's in trouble. OK, 00:18:01.859 --> 00:18:04.470 warning number two, pancreatitis. This one can 00:18:04.470 --> 00:18:06.549 happen at any time after one week on the drug 00:18:06.549 --> 00:18:09.309 or after five years. And it could be hemorrhagic 00:18:09.309 --> 00:18:12.470 and rapidly fatal. What's a telltale sign a nurse 00:18:12.470 --> 00:18:14.829 or a parent should look for? Severe abdominal 00:18:14.829 --> 00:18:17.670 pain that radiates to the back, nausea and vomiting. 00:18:18.250 --> 00:18:20.730 If a kid on Depakote has a tummy ache that seems 00:18:20.730 --> 00:18:22.789 way out of proportion to a normal stomach bug, 00:18:23.190 --> 00:18:24.890 you check an amylase and lipase immediately. 00:18:25.009 --> 00:18:27.049 You do not send them home with Tylenol. And the 00:18:27.049 --> 00:18:30.470 third one, teratogenicity. This is the conversation 00:18:30.470 --> 00:18:32.869 that must break hearts in the clinic. It's awful. 00:18:33.150 --> 00:18:36.349 Yeah, malprolac acid is the most terachetic AED 00:18:36.349 --> 00:18:39.750 we have, period. It has a very high risk of causing 00:18:39.750 --> 00:18:42.450 neural tube defects like spina bifida, where 00:18:42.450 --> 00:18:45.329 the spinal column doesn't close properly. It's 00:18:45.329 --> 00:18:47.950 also been shown to lower the child's IQ. So if 00:18:47.950 --> 00:18:50.390 you have a 16 -year -old girl with generalized 00:18:50.390 --> 00:18:53.190 epilepsy, you have a very, very difficult decision. 00:18:53.630 --> 00:18:55.670 Valproat might be the only drug that controls 00:18:55.670 --> 00:18:58.470 her seizures. But if she becomes pregnant, the 00:18:58.470 --> 00:19:01.150 risk to the fetus is massive. So what's the protocol? 00:19:01.470 --> 00:19:03.509 You have to have a brutally honest conversation 00:19:03.509 --> 00:19:06.190 about effective contraception. You need to prescribe 00:19:06.190 --> 00:19:09.390 high -dose folic acid. But generally, the rule 00:19:09.390 --> 00:19:12.410 is we try to avoid Valprod in any female of childbearing 00:19:12.410 --> 00:19:14.930 age if there is any other viable option. There's 00:19:14.930 --> 00:19:17.890 another weird side effect with Valprod hyperammonemia. 00:19:18.089 --> 00:19:20.410 Yes. It can cause high ammonia levels in the 00:19:20.410 --> 00:19:22.690 blood, even if the liver tests look perfectly 00:19:22.690 --> 00:19:25.009 normal. And ammonia is toxic to the brain. Right. 00:19:25.150 --> 00:19:28.430 It causes encephalopathy. The patient gets confused, 00:19:28.609 --> 00:19:31.549 lethargic, maybe a taxic. If a patient on Valprote 00:19:31.549 --> 00:19:34.470 starts acting drunk or is just incredibly tired 00:19:34.470 --> 00:19:36.750 and out of it, check an ammonia level. We can 00:19:36.750 --> 00:19:39.150 treat it with laxulose or l -carnitine. Let's 00:19:39.150 --> 00:19:41.930 talk about the practical side. Deepakote sprinkles. 00:19:42.529 --> 00:19:44.890 I've seen this prescribed a lot for kids. This 00:19:44.890 --> 00:19:48.250 is a huge nursing tip. The capsules are filled 00:19:48.250 --> 00:19:50.829 with these little coated beads. For kids who 00:19:50.829 --> 00:19:53.150 can't swallow pills, you can actually pull the 00:19:53.150 --> 00:19:55.809 capsule apart and sprinkle the beads onto soft 00:19:55.809 --> 00:19:58.569 food. Like applesauce or pudding. Exactly. But 00:19:58.569 --> 00:20:02.130 the rule is, swallow, do not chew. And why is 00:20:02.130 --> 00:20:05.450 that? Two big reasons. One, the beads are coated 00:20:05.450 --> 00:20:07.410 to delay the release of the drug. If you chew 00:20:07.410 --> 00:20:09.390 them, you break the coating and dump the drug 00:20:09.390 --> 00:20:12.910 all at once. Okay. And two, valproic acid tastes 00:20:12.910 --> 00:20:16.230 absolutely awful. It is incredibly bitter and 00:20:16.230 --> 00:20:18.549 irritating to the throat. If the kid chews it, 00:20:18.589 --> 00:20:20.410 they will spit it out and probably refuse to 00:20:20.410 --> 00:20:22.750 ever take it again. So you put it on a spoonful 00:20:22.750 --> 00:20:24.309 of pudding and tell them to gulp it down like 00:20:24.309 --> 00:20:26.349 a snake. You gulp it like a snake. I'm definitely 00:20:26.349 --> 00:20:28.569 writing that down. OK, so we've covered the heavy, 00:20:28.730 --> 00:20:31.029 dirty, older drugs. Let's move to the newer generation. 00:20:31.490 --> 00:20:33.750 These drugs were designed to be cleaner, but 00:20:33.750 --> 00:20:36.329 they have their own quirks. Let's start with 00:20:36.329 --> 00:20:39.430 Toparomet or Topamax. Toparomet is another one 00:20:39.430 --> 00:20:41.950 of these broad spectrum drugs. It blocks sodium, 00:20:42.170 --> 00:20:45.529 helps GABA, and it also blocks glutamate. But 00:20:45.529 --> 00:20:49.000 it has this unique chemical. property. It's a 00:20:49.000 --> 00:20:51.619 weak carbonic anhydrase inhibitor. That sounds 00:20:51.619 --> 00:20:53.099 like something straight out of chemistry class. 00:20:53.099 --> 00:20:54.799 What does that actually mean for the patient? 00:20:55.240 --> 00:20:57.240 Well, carbonic anhydrase is an enzyme that's 00:20:57.240 --> 00:21:00.420 involved in maintaining acid -base balance and 00:21:00.420 --> 00:21:05.319 sweating. Sweating? Yes. Toiparamid causes oligohydrosis. 00:21:05.339 --> 00:21:07.920 That's the fancy term for little sweating. So 00:21:07.920 --> 00:21:10.799 the child loses the ability to cool themselves 00:21:10.799 --> 00:21:13.700 down. Exactly. So imagine a 10 -year -old on 00:21:13.700 --> 00:21:17.779 top of Max playing soccer in July. They're generating 00:21:17.779 --> 00:21:20.019 all this metabolic heat, but they aren't sweating. 00:21:20.380 --> 00:21:22.099 They're core temperature spikes. They can get 00:21:22.099 --> 00:21:24.640 heat stroke very, very easily. So the teaching 00:21:24.640 --> 00:21:26.779 point for parents is absolutely critical here. 00:21:26.880 --> 00:21:29.579 Hydrate, hydrate, hydrate, and limits. If it's 00:21:29.579 --> 00:21:31.500 a hot day, they cannot stay out as long as the 00:21:31.500 --> 00:21:33.380 other kids. They need frequent cooling breaks. 00:21:33.759 --> 00:21:36.480 It's a major safety issue. And because of that 00:21:36.480 --> 00:21:39.380 same carbonic and hydrous inhibition in the kidneys. 00:21:39.599 --> 00:21:43.450 Kidney stones. It causes a metabolic acidosis, 00:21:43.690 --> 00:21:46.690 which changes the urine pH, and that leads to 00:21:46.690 --> 00:21:49.829 the formation of stones. So again, hydration 00:21:49.829 --> 00:21:52.289 is the number one prevention. Now, Topamax has 00:21:52.289 --> 00:21:55.390 a nickname in the medical community, Dopamax. 00:21:55.470 --> 00:21:58.950 Yes, because it makes you feel, well, dopey. 00:21:59.250 --> 00:22:02.369 Is it just sedation? Like feeling tired? It's 00:22:02.369 --> 00:22:06.259 more like a cognitive dulling. Word finding difficulties, 00:22:06.460 --> 00:22:08.000 you know that feeling where you know what you 00:22:08.000 --> 00:22:09.839 want to say But you just can't find the word 00:22:09.839 --> 00:22:12.200 the tip of the tongue phenomenon all the time 00:22:12.200 --> 00:22:15.559 memory lapses Slowed processing speed for a student 00:22:15.559 --> 00:22:18.680 in school. That is a major major problem It is 00:22:18.680 --> 00:22:21.099 I've had college students who had to stop taking 00:22:21.099 --> 00:22:23.059 it because they literally couldn't pass their 00:22:23.059 --> 00:22:25.380 exams They described it as feeling like they 00:22:25.380 --> 00:22:27.880 were trying to think through mud. It's dose dependent 00:22:27.880 --> 00:22:29.839 So sometimes lowering the dose helps, but it's 00:22:29.839 --> 00:22:32.890 a very real quality of life issue Okay, next 00:22:32.890 --> 00:22:36.529 on the list is Gabapentin or Neurontin. Now, 00:22:36.569 --> 00:22:38.170 based on the name, I'm going to assume it works 00:22:38.170 --> 00:22:40.170 on GABA receptors? You would think so, would 00:22:40.170 --> 00:22:42.289 you? But that is the great pharmacological lie. 00:22:42.430 --> 00:22:45.750 Juggles. Real. Gabapentin was designed to mimic 00:22:45.750 --> 00:22:48.710 GABA, but it doesn't bind to GABA receptors at 00:22:48.710 --> 00:22:51.230 all. So what does it do? It binds to calcium 00:22:51.230 --> 00:22:55.049 channels, specifically the alpha -2 delta subunit 00:22:55.049 --> 00:22:58.039 of voltage -gated calcium channels. By doing 00:22:58.039 --> 00:23:00.819 that, it reduces the influx of calcium, which 00:23:00.819 --> 00:23:03.680 in turn stops the neuron from releasing excitatory 00:23:03.680 --> 00:23:06.819 neurotransmitters like glutamate. So it stops 00:23:06.819 --> 00:23:09.099 the shout before it even leaves the mouth. That's 00:23:09.099 --> 00:23:11.380 a good analogy, yeah. We use it as an add -on 00:23:11.380 --> 00:23:14.160 medication for focal seizures, but in current 00:23:14.160 --> 00:23:17.019 practice, you see it used way more for neuropathic 00:23:17.019 --> 00:23:20.039 pain. Now, gabapentin has a kinetic profile that 00:23:20.039 --> 00:23:23.220 is the exact opposite of phenytoin. Finitoin 00:23:23.220 --> 00:23:26.599 saturates the liver. Gabapentin saturates the 00:23:26.599 --> 00:23:29.440 gut. Correct. Gabapentin has saturable absorption. 00:23:29.940 --> 00:23:31.559 There are only so many transporters in the intestine 00:23:31.559 --> 00:23:33.259 they can pick up the drug and move it into the 00:23:33.259 --> 00:23:35.960 blood. So if I take a massive dose? The transporters 00:23:35.960 --> 00:23:38.119 get full and the rest of the drug just passes 00:23:38.119 --> 00:23:39.900 right through the GI tract and ends up in the 00:23:39.900 --> 00:23:42.579 toilet. So taking 3 ,000 milligrams isn't that 00:23:42.579 --> 00:23:45.720 much different from taking 2 ,000. The bioavailability 00:23:45.720 --> 00:23:48.680 actually decreases as the dose goes up. It makes 00:23:48.680 --> 00:23:51.200 it relatively safe in an overdose. It's hard 00:23:51.200 --> 00:23:53.480 to absorb enough to kill yourself, but it also 00:23:53.480 --> 00:23:55.660 means there's a ceiling to how effective it can 00:23:55.660 --> 00:23:58.559 be. OK, let's move to the rock star of the modern 00:23:58.559 --> 00:24:03.140 era. Leviteracetam or Keppra? Keppra really changed 00:24:03.140 --> 00:24:05.599 the game. It is currently one of the most prescribed 00:24:05.599 --> 00:24:08.220 AEDs in the entire world. Why? What makes it 00:24:08.220 --> 00:24:11.269 so special? It is just so incredibly easy to 00:24:11.269 --> 00:24:14.769 use. It has linear kinetics. It has almost 100 00:24:14.769 --> 00:24:17.750 % bioavailability when you take it orally. It's 00:24:17.750 --> 00:24:19.390 excreted by the kidney so it doesn't chew up 00:24:19.390 --> 00:24:22.650 the liver. And it has almost no drug interactions. 00:24:22.950 --> 00:24:24.670 So you don't have to worry about it messing with 00:24:24.670 --> 00:24:27.490 the patient's other medications. Exactly. And 00:24:27.490 --> 00:24:30.549 the big one, the IV to oral conversion is one 00:24:30.549 --> 00:24:33.109 to one. Explain why that matters so much for 00:24:33.109 --> 00:24:35.950 a hospital nurse. It simplifies discharge planning 00:24:35.950 --> 00:24:38.430 immensely. If a patient comes in seizing, we 00:24:38.430 --> 00:24:40.630 can load them with ID Capra. Once they're awake 00:24:40.630 --> 00:24:43.009 and can swallow, we can switch them to the exact 00:24:43.009 --> 00:24:46.130 same dose in a pill immediately. No complicated 00:24:46.130 --> 00:24:49.670 calculations, no overlap period. None. It's seamless. 00:24:50.049 --> 00:24:54.029 But nothing is ever free in pharmacology. There 00:24:54.029 --> 00:24:56.269 is a side effect that parents warn each other 00:24:56.269 --> 00:25:00.880 about in online support groups. It is very real. 00:25:01.039 --> 00:25:04.220 While the drug is kinetically clean, it can be 00:25:04.220 --> 00:25:06.259 behaviorally dirty. What does that look like 00:25:06.259 --> 00:25:09.839 in a child? Irritability, education, hostility. 00:25:09.960 --> 00:25:12.839 I mean, a normally sweet, calm child can become 00:25:12.839 --> 00:25:15.299 aggressive, screaming, throwing things. It can 00:25:15.299 --> 00:25:17.539 happen within days of starting the drug. Is there 00:25:17.539 --> 00:25:19.480 anything we can do besides just stopping the 00:25:19.480 --> 00:25:22.700 drug? There is some evidence, it's mostly anecdotal, 00:25:22.700 --> 00:25:25.839 but it's very widely practiced, that supplementing 00:25:25.839 --> 00:25:29.559 with vitamin B6 curadoxin can help mitigate some 00:25:29.559 --> 00:25:31.140 of those behavioral side effects. Interesting. 00:25:31.279 --> 00:25:33.740 We often prescribe B6 right along sidekepper 00:25:33.740 --> 00:25:36.339 for this exact reason, but if the rage is really 00:25:36.339 --> 00:25:38.960 bad, we just have to switch drugs. Okay, we've 00:25:38.960 --> 00:25:41.640 covered the maintenance meds, but we cannot end 00:25:41.640 --> 00:25:44.180 a deep dive on PEDS neuro without talking about 00:25:44.180 --> 00:25:46.500 the rescue squad and the absence specialist. 00:25:46.740 --> 00:25:48.480 Right. The rescue squad is for when the seizure 00:25:48.480 --> 00:25:51.299 won't stop. Stance epilepticus. This is a true 00:25:51.299 --> 00:25:54.000 emergency. A medical emergency. The brain is 00:25:54.000 --> 00:25:55.779 cooking. You need to stop that electrical firing 00:25:55.779 --> 00:26:00.000 immediately. And the drugs of choice are? Benzodiazepines, 00:26:00.339 --> 00:26:02.359 lorazepam, which is autovan, diazepam, which 00:26:02.359 --> 00:26:06.119 is valium, or mitazolam, versed. We talked about 00:26:06.119 --> 00:26:08.519 their mechanism with phenobarb. They open that 00:26:08.519 --> 00:26:10.259 chloride channel frequently. They kick the door 00:26:10.259 --> 00:26:13.099 open and shut really fast. Right. They are fast 00:26:13.099 --> 00:26:15.900 -acting, very potent inhibitors. But they're 00:26:15.900 --> 00:26:18.440 also short -acting. They stop the seizure now, 00:26:18.440 --> 00:26:20.519 but they wear off pretty quickly. Which is why? 00:26:20.579 --> 00:26:23.359 Which is why you always follow a benzo with a 00:26:23.359 --> 00:26:26.210 loader. of a long -acting drug like phenytoin 00:26:26.210 --> 00:26:29.490 or kepra or phenobarbital. The benzo stops the 00:26:29.490 --> 00:26:31.430 fire, the loader prevents it from reigniting. 00:26:31.670 --> 00:26:35.109 What is the main safety risk when you push aviadavan 00:26:35.109 --> 00:26:38.650 in a seizing child? Respiratory depression. The 00:26:38.650 --> 00:26:41.309 same mechanism that quiets the brain also quiets 00:26:41.309 --> 00:26:43.490 the breathing drive. So if you stop the seizure 00:26:43.490 --> 00:26:45.130 but the kid stops breathing, you haven't really 00:26:45.130 --> 00:26:47.150 won yet. Right. You have to be ready to bag mask, 00:26:47.289 --> 00:26:49.769 ventilate, or even intubate. Airway is always 00:26:49.769 --> 00:26:54.319 the priority. And finally, the specialist. Ethasexamide. 00:26:54.319 --> 00:26:56.400 Ethasexamide is a one -trick pony, but it is 00:26:56.400 --> 00:26:58.740 a magnificent trick. It is used exclusively for 00:26:58.740 --> 00:27:01.259 absence seizures. Describe an absence seizure 00:27:01.259 --> 00:27:03.420 for us. What does that look like? It's not a 00:27:03.420 --> 00:27:07.259 convulsion. The child just goes away. They stare 00:27:07.259 --> 00:27:09.119 blankly. They might blink their eyes rapidly. 00:27:09.440 --> 00:27:11.559 It lasts for just a few seconds, and then they're 00:27:11.559 --> 00:27:14.079 back as if nothing happened. But it can happen 00:27:14.079 --> 00:27:16.990 hundreds of times a day. It looks like daydreaming. 00:27:17.269 --> 00:27:19.829 It's often confused for ADHD. Teachers are usually 00:27:19.829 --> 00:27:22.150 the first to notice Johnny isn't paying attention 00:27:22.150 --> 00:27:25.869 in class. But actually, Johnny is having tiny 00:27:25.869 --> 00:27:29.210 seizures all day long. And ethosoxamide fixes 00:27:29.210 --> 00:27:32.450 this. Yes. It works by blocking something called 00:27:32.450 --> 00:27:35.829 T -type calcium channels in the thalamus. These 00:27:35.829 --> 00:27:37.750 channels are basically the pacemakers that create 00:27:37.750 --> 00:27:40.769 the specific electrical rhythm of absence seizures. 00:27:41.690 --> 00:27:43.849 Ethosuximide stops that rhythm cold. But you 00:27:43.849 --> 00:27:46.650 would never use it for a tonic -clonic seizure. 00:27:46.869 --> 00:27:49.509 Never. It would do absolutely nothing for a generalized 00:27:49.509 --> 00:27:51.809 motor seizure. It is a very specialized tool 00:27:51.809 --> 00:27:54.690 for a very specific job. We have covered a mountain 00:27:54.690 --> 00:27:56.650 of information. Let's try to synthesize this 00:27:56.650 --> 00:27:59.670 into a don't kill the patient checklist. If you 00:27:59.670 --> 00:28:01.740 are at the bedside, What are the red flags you 00:28:01.740 --> 00:28:03.420 need to have front of mind? Alright, let's run 00:28:03.420 --> 00:28:05.099 through the body system. Okay, start with the 00:28:05.099 --> 00:28:08.119 liver. Valproic acid. Be extra careful in toddlers 00:28:08.119 --> 00:28:10.660 under two. The skin! Carbamazepine is the big 00:28:10.660 --> 00:28:13.619 one. And phenytoin and limatrogeny too. Watch 00:28:13.619 --> 00:28:16.920 for that SJS rash. And remember to screen Asian 00:28:16.920 --> 00:28:20.079 patients for the HLAB Star 1502 allele before 00:28:20.079 --> 00:28:22.859 starting carbamazepine. It's the blood. Carbamazepine 00:28:22.859 --> 00:28:25.640 and valproic acid. Watch for signs of infection. 00:28:25.930 --> 00:28:29.190 Watch for unusual bruising or bleeding. The gums. 00:28:29.450 --> 00:28:32.769 Phenytoin. Dental care is mandatory patient education. 00:28:32.990 --> 00:28:35.930 The temperature. Topiramate. They can't sweat. 00:28:36.150 --> 00:28:38.750 Keep them cool. Keep them hydrated. The IV site. 00:28:39.690 --> 00:28:41.829 Phenytoin. Watch for that purple glove. Push 00:28:41.829 --> 00:28:45.849 it slow. Always. This summary is gold. It really 00:28:45.849 --> 00:28:48.690 shifts the focus from just memorizing lists of 00:28:48.690 --> 00:28:51.309 side effects to understanding real, tangible 00:28:51.309 --> 00:28:53.490 risks. And that's the key to clinical practice. 00:28:53.750 --> 00:28:56.519 You treat the child. not the monitor, but you 00:28:56.519 --> 00:28:58.779 respect the drug. Before we wrap up, I want to 00:28:58.779 --> 00:29:00.240 zoom out for a second. We've talked a lot about 00:29:00.240 --> 00:29:02.839 molecules and receptors and channels, but what's 00:29:02.839 --> 00:29:04.839 the bigger picture here? What is the goal? The 00:29:04.839 --> 00:29:07.660 bigger picture is the trade -off. We are constantly 00:29:07.660 --> 00:29:10.759 balancing seizure freedom with cognitive freedom. 00:29:11.039 --> 00:29:14.380 Explain that. Every single drug we give alters 00:29:14.380 --> 00:29:16.819 the brain's fundamental operating system. The 00:29:16.819 --> 00:29:21.099 old drugs, phenobarb, phenytoin, they work, but 00:29:21.099 --> 00:29:24.549 they are heavy. they sedate, they slow down processing 00:29:24.549 --> 00:29:27.109 speed. And for a developing brain, a child who 00:29:27.109 --> 00:29:31.309 is learning to read, to walk, to socialize, that 00:29:31.309 --> 00:29:34.809 slowing down has a real cost. A huge cost, exactly. 00:29:35.069 --> 00:29:38.069 The holy grail of pediatric neurology isn't just 00:29:38.069 --> 00:29:40.289 stopping the seizure, it's stopping the seizure 00:29:40.289 --> 00:29:43.109 without blunting the child's potential. We want 00:29:43.109 --> 00:29:45.970 drugs that are precision instruments, not blunt 00:29:45.970 --> 00:29:47.730 force hammers. And are we getting there? We're 00:29:47.730 --> 00:29:49.589 getting closer with things like Keppra and some 00:29:49.589 --> 00:29:51.849 of the even newer genetic base therapies, but 00:29:52.190 --> 00:29:54.230 We aren't there yet. So the nurse's job isn't 00:29:54.230 --> 00:29:56.529 just to give the pill on time, it's to advocate 00:29:56.529 --> 00:29:58.789 for the child's quality of life. Correct. You 00:29:58.789 --> 00:30:00.849 have to be that advocate. If the seizure is gone 00:30:00.849 --> 00:30:03.150 but the child is a zombie, we haven't succeeded. 00:30:03.289 --> 00:30:05.349 We need to keep pushing for that balance. That 00:30:05.349 --> 00:30:08.250 is a really powerful thought to end on. Treat 00:30:08.250 --> 00:30:11.170 the whole child. Always. Thank you so much for 00:30:11.170 --> 00:30:13.390 this master class. I honestly feel like I could 00:30:13.390 --> 00:30:15.690 walk into a neuro unit now and really understand 00:30:15.690 --> 00:30:18.190 what is happening in those IV bags. It was my 00:30:18.190 --> 00:30:21.059 pleasure. Just keep those kids safe. To our listeners, 00:30:21.240 --> 00:30:23.400 thank you for diving deep with us. Review your 00:30:23.400 --> 00:30:26.079 kinetics, check your IV sites, and we will see 00:30:26.079 --> 00:30:27.099 you on the next episode.