Drugs for Epilepsy

foreign what's up Ninja nerds in this video today we're going to be talking about drugs for epilepsy before we get started really I urge you guys please if you guys do find these videos helpful and they make sense please support us and I mean this the best way that you really can do that is by hitting that like button commenting on the comment section and please subscribe it just really helps us to continue to keep making free videos for you guys is all enjoyment academic advancement so please check that out please also if you guys

really have a strong interest in really understanding this topic I highly suggest you go down in the description box below there's a link to our website on that we have some amazing notes illustrations that our Ninja new team has kind of whipped up for you guys that I really really think will help you guys in understanding this topic as we go along print off those templates print off those you know illustrative diagrams and follow along with me fill in the blanks I really think it's going to help you guys because then you get a little

bit of that my voice in there you get a little bit of drawing in there you get a lot of visual stimulus I think it just is all those learning Pathways so please do that without further Ado let's talk about the drugs for epilepsy in order for us to do that in order to talk about all these different drugs their mechanism what are they actually used for like how do I know which one's best for which type of epilepsy and then what are the adverse effects all those things that we're going to discuss we have

to get ourselves kind of built on that Foundation of what is epilepsy right and so there's a slight difference between seizures and epilepsy so seizures are generally it's the event of where a patient may be having or exhibiting this High electrical discharge from the central nervous system but if it's kind of a one-time event a one and done kind of thing that's kind of what we classify as a seizure but if they're having multiple seizures like okay so usually two or more seizures that they haven't resolved that it's continuing to happen chronically then we see

a disease of epilepsy so that leads to the question right so epilepsy is when a patient is having continuous recurrent seizures so there's different ways that a patient can seize in other words you could have three types what I really want you to remember is focal generalized and then we call this third one it's like an unknown but we kind of fit this in kind of this random category called epileptic spasms if you had picked two that I really want you to remember it's focal and generalized please don't forget that so when we talk about

focal seizures really there's this particular area in the actual brain in the central nervous system that's becoming agitated like maybe it's here near the cortex and in this region here there's this agitated Focus here where the neurons in this part of the cortex are agitated it's sending these high electrical discharges and depending upon where it is in that part of the cortex depends upon what type of seizure they actually present with just isn't a quick example if a patient had for example irritable area in the right motor cortex what do you think would happen they

might start exhibiting only left-sided type of symptoms so left-sided kind of movements abnormal movements and that's really really important so that's a focal seizure now focal seizures are really interesting because they can happen where you actually have no loss of consciousness or you have loss of consciousness and that determines if it's a focal seizure with impairment or a focal seizure without impairment but on top of that the other concept behind this is that it could be motor it could be sensory so if you hit the sensory cortex there's an irritable area there you may have

abnormal sensation or loss of sensation on that left side so you get the point you can have different types of focal seizures the next one is a generalized seizure in this sense there is multiple areas of the cortex that are agitated irritated and these are sending these irritable types of signals all over look at this this is terrible multiple areas of the cortex are agitated irritated and they're sending all of these high electrical discharges all over these patients usually have impairment or loss of consciousness they don't really remember the event that well okay so that's

a really really important thing is that generalized seizures they often times present with a loss of consciousness or a degree of impairment where they forget everything that happened now with generalized seizures there's different types really quickly one of them that I want you guys to remember here that's that common that scary one that you see is that Grandma that tonic clonic seizure that's one type the next one is where the patient has a really massively increased tone and their muscles are just literally like locked up that's called a tonic seizure then you can have clonic

seizures so you kind of have tonic clonic as a mixed right so clonic is like this so but you have tonic where now you have increased tone and you have that clonic movement so you can have clonic you can also have where the muscles literally go limp not even kidding and it can completely go limp and this is called atonic and then you have another one called myoclonic and this is usually quick jerky movements quick jerky rhythmic rapid types of movements all right there's one more which is also considered to be a part of the

generalized seizures and this is a really interesting one so I want to add this one over here that you guys don't forget so this would be the sixth type and this is called a absent seizure absence seizures are really really kind of sad they happen in young pediatric patients and usually this is classic for them to kind of be in class young pediatric patients staring out zoning out forgetting everything that usually happen during that time period we also call them like petit mal seizures so really important one there the last one just really quickly I

don't want us to go too crazy here we don't really know the actual true mechanism of kind of how this is all happening but there is three particular ones that I want you to know one is called benign rolandic spasms so benign rolandic the second one is really an important one called West syndrome so I really want you to remember this one here West syndrome and the third one is a sad sad case I've seen two cases of this in my neurology team a kind of a patient population but it's called Lenox Gestalt syndrome and

it's a really sad condition where they literally they have multiple seizures every single day and it's almost impossible to be able to control but these are the different types of classification of epilepsy and it's important remember that epilepsy is continued recurrent seizures that happen again and again and again when a patient has seizures we know now that there's focal generalized and epileptic spasms with the emphasis on these two why did I introduce this because guess what different drugs treat different types of seizures so I have a specific drugs that'll treat focal seizures I have specific

drugs that'll treat tonic clonic absence myoclonic seizure so it's really important to remember with an emphasis that I really want you guys to focus on this one myoclonic absent and tonyclonic just being that these are likely going to be the most common types of seizures that you'll see as well as focal seizures and then unfortunately West syndrome is the big one that I want you to remember as well all right that leads to the next question all right we have these irritable areas of the brain tissue that's causing this abnormal discharge of electrical events it's

causing these patients to develop many different things focal seizures could be one limb generalized could be bilateral but they lose Consciousness and it could be tonoclonic tonic clonic atonic myoclonic or they just blank out absence what's the reason that this area of the cortex become so irritable and start sending off these discharges whether it be focal or generalized what is the trigger that's the question right what is the thing that's activating or triggering this particular Focus now that's what I want you guys to be thinking about and I want you to remember the mnemonic vitamins

or actually I'm sorry vitamin d e okay so V is for vascular etiologies and so if there is some type of bleed within the brain that can cause an irritable area of the brain just a quick example if someone has a bleed if someone has a subarachnoid hemorrhage if someone has an acute ischemic stroke those are particular areas where you damage that tissue now it can become irritable I is infectious so if someone has things like meningitis or Encephalitis I'm just going to put m e meningitis or Encephalitis this could be a potentially irritable kind

of focus or because the meninges are right next to the cortex T trauma so sometimes if someone bangs their head and they get a bleed that's kind of compressing and irritable kind of focus to the brain tissue here such as a epidural hematoma a subdural hematoma these are other ones autoimmune so this could be a patient who has an underlying autoimmune disease examples could be something like SLE and they trigger antibodies and these antibodies go and attack parts of the brain tissue and cause irritability and inflammation of the brain tissue sometimes it can even be

something called perineoplastic where you have a Cancer and then that cancer produces antibodies so if you really wanted to remember that you could add a second one called Para neoplastic all that means is to give an examples I have a tumor here here's my tumor cell it produces antibodies and these antibodies go and attack the actual cortex of the tissue all right so that's the part for vitamin Ray so we're almost there m is metabolic and this Believe It or Not tends to be pretty common there's many different things one that I really want you

to remember is hyponatremia believe it or not high or low glucose can do this and things like thyroid disorders lipid disorders those are also big ones as well I another I is idiopathic meaning we don't really know why this happens this tends to be these epileptic types of disorders that I want you to remember the next one is neoplasia and this is obviously really sad but someone has some type of mass right they have some type of primary Mass like a GBM they have a metastatic lesion that spread from somewhere else sad sad case is

there and then the other one which believe it or not is very very common drugs and toxins and this list could be never ending in so long we can't go through all of them but remember that and then the last one is that pregnant patient the eclamptic patient so eclampsia would be another particular one to remember as well all right so the basic concept is we have things that can trigger patients to have seizures the vitamin D and E would be the things that can trigger this area to become irritable cause that cortex to start

sending off these high electrical discharges which if it causes only one arm or to have motor movement or sensory loss then it could be a focal seizure if it's complete loss of consciousness bilateral generalized tonic clonic seizures that could be one type of presentation they could also be completely tensed up tonic they could have some type of movement like this clonic they could go limp atonic they could have rhythmic discharging kind of rhythmic movements myoclonic or they could have absence where they lose Consciousness and then completely blank on stair the next question that you have

to ask is okay I know the thing that triggers this I know if this thing becomes irritable what it can present like if we get down to the neuronal level what's actually happening there let's talk about that so what I wanted to do is I want to kind of zoom in on this irritable area the irritable area in the brain where there's this trigger of kind of seizures it could be one area it could be the entire cerebral cortex right and that's kind of the basic concept between generalized and focal seizures now it is important

to remember that a patient can have a focal seizure that's secondarily generalizes in other words you could have this Focus here where a patient has electrical discharges and then at some point they lose Consciousness and have bilateral kind of all extremity involvement so you can have a patient who has focal seizures that progresses into a generalized honoclonic seizure so that's important but nonetheless if we zoomed in on these areas of irritability within the cortex and we looked at this neuronal type of diagram this is really where it's important so let's say here's the neuron here's

the neuron that's the problem and it's sending these Action potentials down the axons that are triggering this seizure activity if you will right this is the neuron that's giving us some problems there's other neurons that influence this particular neuron okay this is our seizure neuron what I really want you to remember is the basic kind of mechanism behind this is that you have too much glutamate activity that's one particular reason is high glutamate activity that can cause seizures I'll explain why that why that is in a second the second one is there's a very little

gab activity so there's very low or decreased Gaba activity and it's these two particular things that are the primary kind of reason why patients develop these seizures let me explain here's a neuron and this is a glutaminergic neuron in other words it releases out of these axons here out of this neuron it releases the chemical called glutamate so all of these little circles here are called glutamate now the way that this neuron releases glutamate is important because it's going to come into the drugs later here we have an axon here right here's the axon of

the neuron on the axon there's these special channels called voltage-gated sodium channels I'm just going to mark this as 0.1 so 0.1 is the voltage-gated sodium channels when these become active sodium we'll rush into the cell and make the axon positive right so engage in what's called depolarization that depolarization is the thing that triggers the Second Step so we have sodium rushing in that triggers the depolarization of the axon that depolarization of the axon then stimulates these next channels the second Channel the second one is these green channels called the voltage-gated calcium channels whenever sodium

rushes into the axon it depolarizes the axon then it opens up these voltage-gated calcium channels and calcium will flood in when calcium floods in the reason why it's so special is it binds on to these different types of vesicles these proteins on these vesicles which helps the vesicle to fuse with the cell membrane and release out the glutamate so there's another important part which is the you need these particular types of proteins or receptors to bind calcium or to fuse with the cell membrane that's a third point the next thing is that the glutamate that's

when it's released into the synaptic cleft has to go here and bind onto these little pockets here called these different types of receptors these are special special receptors here where it binds onto and triggers these channels to open when they open they lead to things like sodium and calcium rushing in to the actual cell when it rushes into the cell these things do what they increase the action potential type of pathway so then you get an increase in the action potential path which causes an increase in seizures why because they depolarize this neuron they make

it super super positive so they're going to make this neuron super positive and cause it to depolarize so if you have excessive glutamate release this is going to cause an increase in the action potentials from this irritable Focus area huh okay let's come to the other part here's a gabergic neuron meaning that when this neuron releases particular chemicals from this actual neuron it releases all these like blue dots here you know what these blue dots are called shocker right it's called Gaba gamma aminobutyric acid now the this gamma butyric acid is very very special in

the sense that when in order for this one to get released there usually is an action potential that comes down the axon right so there is some type of action potential that comes down these axons but there's no special channels that are relevant to the the pharmacology what it'll do is it'll lead to the stimulation of these vesicles to fuse with the membrane and release Gaba Gaba will then go and bind onto this particular types of protein here and this is called a Gaba a receptor I really want you to know this as again the

fifth Point here because this is a very specific point if we can have again Gaba bind onto this receptor it should do what normally it should allow for chloride ions to come into the cell if chloride ions come into the cell what would be the effect then the effect is that if you have chloride ions it'll make the cell super negative and that will do what that'll try to inhibit the increase in action potentials right so it's going to try to hyperpolarize the cell but the problem is is that there's some type of dysfunction at

the Gaba a receptor where this doesn't work if this doesn't work you get less chloride influx and you get less inhibition of this actual hyperpolarism you don't hyperpolarize as much so therefore you end up causing stimulation of an increase in action potential so again I want you to remember normally Gaba will cause chloridines to influx hyperpolarize the cell and inhibit Action potentials but in this disease you're not making a lot of Gaba or producing enough Gaba or The receptors aren't responding to the Gaba so therefore chlorines don't flow in they don't inhibit Action potentials and

instead they lead to the stimulation of action potentials that's that's not that's not fun okay well the next thing is the Gaba once it's actually released it has to get recycled and when it gets recycled it's important to know that in this particular thing if there was a particular way which Gaba maybe there's a lot of uptake now there's less Gaba present here in the actual synapse so sometimes this is another thing where there's an increase in Gaba reuptake and there's less of this Gaba available to bind onto the receptors cause chloride ions to flow

in inhibit Action potentials but if you're taking a lot of it in there's less Gaba less ability to get chloride in less ability to inhibit the action potentials and seizures occur there's another step and there's another one one more in here which is I'm going to get rid of this part here I'm going to get rid of this part here when Gaba comes in back in to the actual neuron it can get recycled or it can get metabolized and it can be turned into an inactive metabolite and so if there was a potential process here

on this seventh step here where there was a increase a increase in the breakdown of Gaba there'll be less Gaba that can be recycled less Gaba released less Gaba to bind onto the channels less chloride coming in less hyperpolarization therefore you're going to depolarize and stimulate Action potentials and cause seizures that's the process that I really want you guys to remember here and the reason why is I'm going to give drugs to block the sodium channels that'll block glued memories I'm gonna give drugs that block calcium channels that'll block glutamate release I'm going to give

drugs that block these proteins from fusing with the cell membrane therefore these vesicles won't fuse and release glutamate I'm going to give drugs that block these receptors that allow glutamate to bind to them and cause ions to flow in and Trigger action potentials I'm going to give drugs that stimulate the Gaba a receptor increase chloride and influx if I do that I'll cause the cell to hyperpolarize and inhibit Action potentials I'm going to give drugs that inhibit the re-uptake of of Gaba so that more Gaba stays in the synapse binds to these receptors causes chloridine

influx hyperpolarize and inhibits Action potentials I'm gonna give drugs that prevent the breakdown of Gaba so that more Gaba is getting recycled being released finding on inhibiting action potentials and that is the next step that we have to talk about which is the mechanism of action and the names of all these different drugs all right my friends so now we've kind of got to the point that we know that one of the pathophysiological points or the mechanisms behind epilepsy is that there is again an increase in action potentials and these increases in action potentials are

leading to an increase and these seizures that we see whether it be focal or generalized right but we said that the basic reasoning behind one of them was that there was an excessive increase in the glutamate activity so now what I want to do is I want to come up with a mechanism right so the increase in glutamate activity was really causing this problem it was leading to increased Action potentials and then subsequently increase seizures so my goal is I want to come up with drugs that are going to inhibit that glutamate activity and so

my end goal is to decrease the action potentials within this neuron and therefore decrease the electrical discharge is leading to decreased seizures so how do I do that great question first thing is I want to block the sodium influx if I can block sodium influx I prevent sodium from coming in so I'm going to inhibit sodium influx then I won't lead to depolarization I won't depolarize I'll inhibit the depolarization if I inhibit the depolarization then I won't stimulate these particular channels called calcium channels I won't allow calcium to flow in I won't allow the calcium

to bind with the vesicles to fuse with the synaptic membrane and to release what chemical out here glutamate I won't allow glutamate to bind onto these receptors causing sodium influx calcium influx which both collectively depolarize in lead to a what a decrease in action potentials and a decrease in seizures so if I block the sodium Channel I block all the downward Cascade effect so that's where these drugs come into play because they're going to do again what they're going to work on inhibiting these particular channels so that deserves the question what are these drugs so

first one that I want you to remember here is carmazepine carbamazepine is a really great drug carbamazepine another one is a close friend or cousin of it which is called oxcarbazepine another good drug that you can actually put in this category is called phenytoin and then it's cousin phosphonatoan another one is called lamotrigine lamotrigine another one is called Topiramate and then the last one that I want to put in this list is what's called valpro 8 there is another one called licosamide you can also add that one in there I'll just do it for you

guys there's another one called lookosamide as well so these drugs all have the ability to inhibit this particular Channel prevent glutamate release Downstream which leads to decreased stimulation of these neurons decrease Action potentials and decrease seizures cool that's it this is the most challenging group to remember because there's so many dang drugs in it go through it a couple times write it out a couple times and just keep trying to go through it I wish I had a trick a mnemonic to help you guys remember it I don't I apologize but just keep trying to

go through these a couple times all right next one is the calcium channel blockers the calcium channel blockers again they're going to inhibit this calcium influx if you inhibit the calcium influx calcium won't be able to come in if calcium can't come in it can't stimulate the fusion of these vesicles with the membrane it can't release glutamate it can't stimulate these actual neurons to cause sodium calcium influx it doesn't allow Action potentials and it decreases seizures it's pretty straightforward right so calcium channel blockers the big one that I want you to remember is called Etho

succimide now back in the day we used to use another drug category I'm not going to put them in here because we don't utilize them for seizures as much anymore but we used to use drugs that would bind to an alpha subunit on the calcium channel and inhibit that which would allow the calcium to go into the actual neuron and this used to be for gabapentin and pregabalin we don't utilize those as much anymore for seizure or epilepsy again it's more for like your neuropathy types of pain and situations like that so ethosoxamide actually this

is an eye ethosoxamide is going to be the primary one that I really want you to remember here okay the next one is what if I block the third point which is I block or I inhibit the fusion right I inhibit these particular cute little proteins these little sv2a proteins synaptic vesicle proteins that are supposed to fuse with the cell membrane when they get Bound by calcium they're supposed to fuse with the cell membrane and then release glutamate if I inhibit that they don't fuse they don't release glutamate doesn't bind onto these channels doesn't allow

sodium calcium influx doesn't cause depolarization doesn't cause Action potentials doesn't lead and then inhibits seizure production this drug is going to be a heck of a one here called Leva teracetam Leva teracitam this is actually a really really great drug very very little adverse effects and it's just very very effective all right next thing so we block sodium influx which led to inhibit depolarization calcium influx and all the downstream effects calcium channel blockers ethosoxamide blocking the vesicles sv2a receptor blockers then we can block the glutamate from binding onto this receptor or this receptor this one

here is called an ampa blocker blocker so we're going to inhibit this particular channel here preventing glutamate from binding into it and causing sodium influx the primary drug in this one is called felbamate it's called felbamate then we have another one which is going to inhibit this particular one and that's the nmda receptor blocker and this primary one that I want you to remember is going to be ketamine all right so from this what I really want you guys to understand is there's drugs that'll help to be able to block the seizures or inhibit seizure

production by doing what decreasing the glutamate activity their whole job is to do what all of these drugs these aeds all of these aeds will do what they will work to inhibit the increase in glutamate activity and that includes sodium channel blockers calcium channel blockers sv2a receptor blockers as well as ampa receptor blockers and nmda receptor blockers beautiful well then that leads to the other mechanism which is the patient who had very little or decreased gab activity what if we had aeds that could increase gab activity let's talk about those so again we said that

whenever patients are having seizures right there's a generally these neurons here the problem they're having an increase in action potentials and one of the reasons why was that there is a decrease in what there was a decrease in the Gaba activity so Gaba wasn't binding onto these receptors well as you weren't having enough Gaba you weren't releasing enough Gaba Gaba wasn't binding The receptors appropriately whatever it is and the result of that is that decreasing gab activity led to less hyperpolarization and so that increased the action potentials and then subsequently increase the seizures well now

what I got to do is I got to come up with some aeds here some different types of anti-epileptic drugs that'll help to inhibit this decrease in gab activity in other words we want to increase gab activity how do I do that great question well the first thing is Gaba is going to fuse right so there was no specific kind of sodium calcium channel type of blocking activity there was no specific type of synaptic vesicle proteins that were relevant that we discussed in the mechanism here it's just we know that Gaba is released from these

gabergic neurons when gaba's release what it does is it binds on to this particular protein or this receptor and this is called a Gaba a receptor when it binds onto this Gaba a receptor what it does is it causes chloride ions to influx into the cell that's naturally what should happen when chlorine ions influx into the cell it makes the cell negative and what that means is it causes the cell to hyper polarize and if it hyperpolarizes it decreases the action potentials and that will decrease effectively that seizure production so that begs the question is

there some way somehow I can have drugs that could bind onto this Gaba a receptor stimulate the son of a gun or increase the activity in its response to Gaba Absa stinking lutely and that's called Gaba a receptor Agonist they're going to bind to the gab a receptor and increase the activity of that receptor acting as if Gaba was already binding what are those drugs so if we stimulate this more chloride will flow in more hyperpolarization decrease Action potentials decrease seizures these drug categories the first one that I want you to remember is called benzo

diazepines and there's so many in this particular category I'm only going to list the relevant ones so the relevant ones include lorazepam this is a big one midazolam is another big one diazepam is another big one and there is a few other ones such as clabazam which is a newer type of benzodiazepine and clonazepam as well but these are one great drug where they have the ability to bind onto these Gaba a receptors and increase this is keyword keyword here I can't stress this enough they increase the frequency of the opening of the chloride channels

in other words when benzodiazepines bind onto these Gaba a receptors they increase the frequency at which those channels open and allow for chloride ions to flow in there's another drug that also does this and this is called barbiturates barbiturates now barbiturates include drugs like phenobarbital and another one called pentobarbital and these drugs are really really powerful extremely powerful and what they do is they bind onto the Gaba a receptor cause it to open up but keep it open very long so they increase the duration they increase the duration of the chloride Channel opening you know

how someone told me to remember this Ben the husband would like to have things with his wife more frequently all right whereas Barb the wife would like Ben to be able to do things a little bit longer in duration so that's how I was helpful to remember this in one of my classes in Pharmacology and I think that this has stuck with me since I hope that helps you so these are the big big drugs that have this ability there's another one another one that I really want you to remember here is Propofol so propofol

is a very powerful type of medication that also has this ability another one that you can also add into the mix here it's called to Pyramid well you're like wait wait to pyramid didn't I see that drug up there before absolutely you did so just remember that to Pyramid I'm going to represent this kind of in a two different color here has an ability to decrease glutamate activity and it has the ability to increase Gaba activity which is pretty cool all right so Topiramate has kind of a dual action and a lot of these drugs

do have dual actions I'm just going to mention a few that are actually pertinent all right so there's one way that we can do this one way that we can increase gab activity is by giving drugs that bind onto the Gaba a receptor to open it up cause chloride ions to influx in there and cause hyperpolarization decrease Action potentials these are the drugs here that I want you to remember with the emphasis on benzodiazepines and barbiturates and then the emphasis on which one increases frequency and which one increases the duration Ben likes it more frequent

Barb likes it longer all right next thing we also said that another problem is that when Gaba is done performing its action it gets taken back up into the actual axon and then two things can happen one is once the gab is inside it can get metabolized into an inactive metabolite right or it could get recycled back up into this actual vesicle but some of it could get broken down what I would like is maybe if I keep as much Gaba out into this actual space it can bind onto more of the Gaba a receptors

cause more chloride influx and then cause a decrease in action potentials so I'm going to give a drug here that inhibits this Channel so then Gaba won't get taken back in if Gaba doesn't get taken back in then the Gaba will be in higher levels in this actual synapse and it'll have more powerful stimulation of these receptors more powerful chloride and influx more hyperpolarization decreased Action potentials and decrease seizures what is the drug that actually does this to be honest with you it's not really utilized that much unless it's very refractory partial seizures and that's

the only time that we're going to mention it is this is called tyaga Bean and I'm just going to mention this here it's not frequently utilized it's primarily utilized in focal seizures so it's primarily utilizing focal seizures that are generally pretty refractory to a lot of your first line therapy which we'll talk about all right all right the last thing is okay we either binded the Gaba a and increased its activity we inhibited the Gaba reuptake protein so that we keep more of it in the synapse to bind to the gab a receptors or we

prevent the breakdown so in other words what if we did this what if we said okay Gap against brought back in yes it's going to get brought back in how about I make sure most of it almost all of it gets recycled back into this vesicle and I basically don't allow this process to occur here I'm going to inhibit this enzyme so that I don't make any of this inactive metabolite and most of it goes into this actual vesicle so that I can increase the amount of Gaba that's getting released with every neural stimulus hmm

that sounds pretty interesting and the drugs that actually do this that I want you to remember called vigabitrin VI gabatrin and then the other one is called valproate and you're like wait a second valproate that sounds familiar it sure does my friends valpro was a sodium channel blocker like to Pyramid which means that like Topiramate valproide has the ability to do what decrease the glutamate activity by inhibiting the sodium channels like the pyramid and it also has the ability to increase the Gaba activity by inhibiting the breakdown of Gaba into the inactive metabolites was to

Pyramid bind onto the Gaba a receptors and act as an Agonist beautiful process of all of these drugs so that's what I want you guys to remember when you go through here okay which is the drugs that basically increase gab activity and which are the drugs that decrease decrease glutamate activity that's the process now we had to go on to the next step which is we have a patientos focal seizures generalize seizures right we found the underlying cause we treated the underlying costs but they continued to have seizures now they have epilepsy we have to

then say okay which drugs could I give that'll stop this focal or generalized seizure which is going to be treated by decreasing their glutamate activity or increasing their gab activity so let's find which drugs are best suited for that specific type of seizure and we're going to focus on first line medications let's talk about it all right my friends let's now talk about how we're going to approach treating epilepsy particularly utilizing anti-epileptic drugs so one of the first things is okay we obviously can give medications to patients who have epilepsy but you have to treat

the underlying cause so if the patient has a particular cause that can be reversed and then they don't require an anti-epileptic that's great so again you have to be able to remember that so just a quick caveat here is just remember always treat the cause the reason why is they may not require they may not need an anti-epileptic drug all right but if you found it there you've gone through you've tried to treat the cause they continue to have seizures or they have no identifiable cause that you've been able to elucidate then you're probably going

to need aeds to continue to suppress or prevent their seizure activity so that's the first thing so I have epilepsy right I've tried to treat the cause or I've tried to find a cause and see if they don't need it but if they do need it I need to find which AED I can pick for the patient that is going to be the best suited it's best found for their evidence to treat that particular type of seizure disorder and doesn't have any significant adverse drug reactions if I've gone through that and the patient is seizure

free okay then I'm done I don't have to do anything else that's great but if the seizures continue to persist so the patient continues to have seizures then I gotta go and I gotta think okay well maybe this wasn't the best AED so then I got to look at doing a second AED and then I got to start decreasing the first AED so start down try down try titrating the first AED so that's the whole point within this one so a patient has epilepsy you have to find the underlying cause treat that if you treat

it they get better they don't have seizures then you don't maybe need to put them on an AED if they have no identifiable cause or they've treated the cause and they continue to have seizures put them on the first line AED that fits that particular seizure disorder with minimal adverse effects if they're seizure free great if they have seizures or they have significant adverse drug reactions which we're going to talk about next add on a second AED titrate that to the therapeutic level and then down titrate the first AED and get that one off if

they have no seizures after that great well then I found the best AED that reduces seizures and has very little adverse drug reactions but if the patient continues to have seizures or they have adverse drug reactions to the second AED then I need to consider two options one is a combo therapy in other words I may need two aeds I may need something like levitarazatan and oxcarbazepine or carbamazepine to be able to meet that particular demand to stop the seizures or I need to pick a third AED and then get down decrease the actual second

80. so down titrate that second AED maximize the efficacy of the third AED so again that's the big big concept that I need you guys to understand to come in epilepsy start them on a first one they stop having seizures great they have seizures or they have adverse drug reactions pick a different one and then get rid of the first one they have no seizures great you found the perfect drug they continue to have seizures or adverse drug reactions get rid of the second one and pick a third one pick a different one this would

be the third AED in this particular situation and then down titrate the second or you can pick two aeds oftentimes most patients two-thirds out of the most epileptic patients can respond to monotherapy but if they require combination that's when you have to kind of think about that with adverse drug reactions if the patient continues from this tab no seizures great we found the best particular scenario for this patient whether it be an alternative AED that third AED or a combo if they continue to have seizures or they have an adverse drug reaction then we're out

of the possibility really of being able to maintain these seizures properly with aeds oftentimes we need to go to something like a VNS which is like a vagal nerve stimulator okay that's outside of the window of this discussion so that's the whole concept that I need you guys to understand a patient comes in they have epilepsy you try an AED first line for that particular situation doesn't work they have adverse drug reactions pick another one pick one that's going to be a better option so that's the second AED they continue to have seizures or adverse

drug reactions get rid of the second one try a third one that has an alternative type of therapy and if that's maybe not best then do combo therapy maybe you need two ads to suppress the seizures and if they're still having seizures then oftentimes you need to go to consider other alternative options all right beautiful that's the thing going to lead us into the next step here how do we treat all the specific types of seizures so focal seizures when a patient has a focal seizure really the big thing is that these patients have specific

anti-epileptics that have been researched to be most effective and what are those anti-epileptics oftentimes this is one that I really want you guys to remember because it's likely to come up on your exam is carbamazepine I am a huge fan of this one it's cousin the carbamazepine I really like this drug I found it to be very very effective and my personal practice was shutting down focal seizures other drugs that have also been pretty good is levitarazatam so levitaracetam is another one that's very very good here and then another one that's also been shown to

be good a little bit is the lamotrigine there's other drugs that can be considered as second line options things like phenytoin phosphenitone valproate to Pyramid you can consider those particular drugs those are going to be the alternative or second line agents the big ones that I really really want you to take into consideration is the carbamazepine and the oxcarbazepine these are big ones one other one that I want to put down here just in a different type of color here are just to kind of highlight here is phenobarbital so phenobarbital can be utilized to shut

down these focal seizures but it's a very specific population I want you to remember phenobabytol you know that sounds dumb but phenobabytol because this is best in neonates so this is Basin neonates and this is actually really important I don't want you guys to forget this okay so we can use phenobarbital in neonates who are having focal seizures these are the big ones that I want you to remember what about the generalized apps on seizures right so apps on seizures everything goes blank right you come back later and you're like man what that happened in

those particular situations there's three well there's a couple but ethosoxamide is going to be the preferred agent if that's not an option valproate is another one and lamotrigine is another option but again I think it's really really high yield to remember that ethosoxamite is that preferred type of treatment especially in the younger children adolescent type of children who have generalized apps on seizures okay we move into the next situation here which is all right we have focal seizures we have generalized absence seizures what about if we come down here generalized myoclonic seizures and then generalize

tonic clonic seizures let's talk about those so the next one here is your generalized myoclonic seizure so in this one again that kind of like rhythmic type of consistent movement repetitive movement in this particular situation one thing that I found is that valproian evidence is found is that valproate is very very effective another one would be levitarazatan this is very very good as well of being able to shut down those seizures another one is um there's been some degree of efficacy with like Lamotrigine as well so Lamotrigine is another one and then benzodiazepines benzodiazepines these

have also been shown to be very very effective but I'd say the most important ones is going to be valproate and levitaracetam these have been shown to be very effective being able to treat myoclonus or myoclonic seizures all right now we come to the generalized tonic clonic seizures and generalized tonic colonic seizures that Grandma's seizure the really scary one how do you treat this one oftentimes valproate is a very good option valproate is very good another one would be levitarazatam is a very good one as well Levitz aracetam Lamotrigine has been shown to be somewhat

beneficial as well until Pyramid has been shown to be somewhat beneficial now there is varying evidence on this right but some will even say that phenytoin phosphen atone is also pretty good in this particular situation so phenytoin and then it's causing phosphonetoin have also been shown degree to some degree to have an efficacy as well and then another one which I don't want to forget here is Fino baby tall right our phenobarbital so phenobarbital remember and babies are neonates this tends to be very effective at being able to shut down those generalized tonic colonic seizures

and neonates which is really sad but please don't forget valproate levitarazatam phenytoin phosphonotonin and phenobarbital especially in these neonates all right so we've covered at this point we've covered the specifically focal seizures we've covered the absence we've covered the tonic clonic in the myoclonic seizures let's now talk about the next thing which is what if a patient has whether it be a focal seizure that continues and they lose Consciousness or generalized seizure and they continue to cease for more than five minutes or they seize and then they have again a little break but then they

seize again without a complete return to their functional Baseline then we have status epilepticus how do we treat those all right my friends so now we have a status epilepticus patient in this particular scenario we often do these in a very specific order so we'll start off in this patient with benzodiazepines right so we always start off with benzodiazepines and again this goes back to this being the first type of Step so you start off with these when a patient comes in you give them Lorazepam diazepam midazolam one of those two after that then you

move on to the next step which is adding on one of the other drugs that's going to prevent recurrent seizures so it's as a prophylaxis so this is where you can use drugs such as phosphen atone is way more preferred in status as compared to phenytoin valproate is another potential option here levitarazatam is another potential option here and then I've also come to be fond of licosamide as well but these are basically prophylactic of being able to prevent seizures when a patient is in status epilepticus then from there if a patient still has seizures they're

instilled in status despite benzos and one of these agents then oftentimes we do something like Propofol or ketamine and then if they still are kind of having seizures we move to the last line which is usually going to be the last step here which is going to be barbiturates so barbiturates would be the last step here and this again would consist of which particular drugs this would consist of your phenobarbital or pentobarbital and generally when a patient requires barbiturates to the point of a pentobarbital state they're usually at the point of almost needing to go

into a coma but this is how we would treat status epilepticus now moving to the next state which is this epileptic spasm so an epileptic spasms again there's the benign rolandic the West syndrome and Lenox gastot syndrome there's one particular drug that I want you guys to remember here and this is Lamotrigine so Lamotrigine that's all I really want you guys to remember for this particular one here but again to highlight here benzodiazepines very very important and then this is very very important for remembering a status epilepticus Lamotrigine is the only agent that I really

want you to remember here and thankfully there's only one specific agent that's high yield for West syndrome and this is called vigabitrin this is called vigabitrin all right let's talk about the last one which is the linuskast thought syndrome For linnig's Thought syndrome is a really really sad case I've seen two of these in practice and they're just terrible for these ones they often are refractory okay so you can give them multiple anti-pileptics oftentimes they're still going to be continuing to have seizures so some of these options that we can consider in this particular situation

valproate tends to be very good another one that you can consider here is to Pyramid so to pyramid is also a pretty decent option Lamotrigine is another potential option here um another one that I would also consider here which we did not mention but just for consistency sake canopy dial this has actually been shown to be very very effective in patients who have Linux thought syndrome and then from there we go into another drug which is usually if they're super super refractory we can consider something like felpamate but oftentimes these patients require vns's as well

as generalized toniconic seizures that are uncontrollable the next custod syndrome that's uncontrollable and then also focal seizures that are uncontrollable sometimes require vns's all right my friend so now we're on to the last part which is adverse effects of these aeds so we kind of talked about how when a patient comes in right they're having focal seizures or generalized seizures we know that the basic concept the basic pathophysiology is there's increased glutamate and decreased gab activity right that's the basic pathophys and then we also have all these causes that we talked about but whenever we

have a patient who has these we have to think about okay what kind of drugs could I give that would actually help to either turn down good made activity or increase gab activity right we went through all those whether it be a sodium channel blocker calcium channel blocker sv2a receptor blocker ampa and MDA receptor blocker to shut down glutamate or agaba a Agonist a Gaba reuptake inhibitor or a Gaba transaminase inhibitor we talked about all those then we said okay the patient has a focal seizure we're going to give them this drug if they have

generalized tonyclonic this one Etc the choice of picking one of those drugs obviously comes from which has been shown to be most effective in this disorder and believe me I know it's going to be tough to memorize that entire list go through it write it down with me take a little break go back write them down again write them down again just keep doing them to see if you guys can help yourselves through repetition go back through these there's no beautiful easy way unfortunately to remember those except for just unfortunately a little bit of brunt

memorization but to help you for when the questions come up on the exam this is where it's really helpful so you're stuck between okay a patient has having focal seizures which one do I give them do I give them carbamazepine oxcarbazepine do I give them love a terazotin do I give them Lamotrigine really it's thinking about the adverse effects that are actually concerning so let's go through these which one of these drugs would cause significant cardiac and respiratory depression in other words they could cause things like bradycardia they can cause low blood pressure they can

cause a decrease in your respiratory rate and the decrease in your depth which are drugs that have the ability to do this and the ones that I really want you guys to remember is going to be your benzodiazepines so your benzos your barbiturates are really really powerful and then the other one here is going to be something like what else Propofol propofol is going to be another one to some degree things like phenytoin phosphenytoin they can cause that as well but it's more likely the sedation that they cause so they cause a degree of central

nervous system depression which can cause a small degree of bradycardia hypotension and decrease respiratory rate and depth but not directly these are the most profound ones I want you to remember the next thing is Steven Johnson syndrome everything is nasty right so basically the patient has just multiple types of rashes positive types of nikolski sign all those different findings and usually the most common ones is Ethan Carl and Larry you're like what the stink is he talking about so this is Etho suxamide ethosoxamide for Ethan coral for carbamazepine carbamazepine and then Larry for Lamotrigine these

tend to be the most common offenders of Stephen Johnson syndrome there's some that say like phenytoin phosphen atone as well but these tend to be the ones that are most associated with it and the most likely ones to come up on the exam okay the next thing here is whenever a patient has hepatotoxicity so in other words if a patient has some type of underlying liver disease it may be a good idea to avoid giving these particular agents and pick another one what are those so sums that are actually going to be particularly good that

can cause a lot of liver damage and may require monitoring because whenever there's liver damage there's some degree of increase in things like your lfts your AST alt alcohols Etc these particular drugs have been shown to be able to cause this so things like valproate is a really big one carbamazepine can also cause this carbamazepine another one is going to be feldomate and this is that really really powerful refractory one that we can see in Linux Gustavo syndrome so these are the particular ones that I want you guys to remember to some degree phenotonin phosphonatone

but nowhere near as powerful as these particular ones all right we come to the next thing which is these drugs can have drug to drug interactions in other words you give these particular drugs they have the ability to act on the cytochrome p450 system inhibit it or induce it so you know that inducers do what they stimulate the cytochrome p450 system so they want to stimulate the cytochrome p450 system so that you break down the drug more quickly and you decrease the efficacy of the drug so you decrease the drug levels of something else so

if you're taking this anti-balaptic plus another drug you're going to decrease the efficacy of that other drug whereas cytochrome p450 Inhibitors they're going to inhibit the cytochrome p450 system so they don't break down the drug and this would potentially increase the concentration of the drug making it super therapeutic these are going to be things like barbiturates right so barbiturates so this is going to be your phenobarbital your pentobarbital these are very very powerful cytochrome p450 inducer so they will decrease the efficacy of other drugs other ones that you want to remember is going to be

something like phenytoin phosphonotonin but more specifically we found that phenytone is a little bit more powerful so phenytone is a really really big one here and the last one is carbamazepine so carbamazepine karba Mazza pain now when we have all of these particular drugs here again it comes down to which one do I pick which is the one that's again going to have the least adverse effects so these have a pretty decent adverse effect profile if it's going to cause a lot of drug drug interaction the one that really causes cytochrome p450 inhibition which can

increase the efficacy of other drugs is going to be valproate so that's what I really want you to remember so again a quick recap here cardiac respiratory depression benzos barbiturates and Propofol Stephen Johnson syndrome Ethan Carl Larry ethosexamide it's going to be then the next one Lamotrigine and then last one is going to be carbamazepine hepatotoxicity valproate carbmazepine and feldmate and then cyp 450 interactions in other words it can alter the efficacy of other drugs the ones that'll decrease the efficacy of another drug would be carmazepine phenytoin and barbiturates and the ones that can actually

do what increase the efficacy of another drug it is going to be valproate all right let's now come down and talk of which drugs are actually dangerous in pregnancy or child-bearing women and then some specific adrs that may come up in your exam all right so teratogenic meaning that it's actually very dangerous to women who are pregnant or of childbearing age and looking to have a child you have to be able to remember these so what are some of these these particular drugs that I really really want you to remember here is going to be

valproate this one is likely to be the most stratogenic and the reason why is it can cause a lot of inhibition of folate production which can lead to something called neural tube defects and this is really really sad you don't want to really see this in patients so be very cognizant and try to avoid these particular agents in a patient who is pregnant another one would be your phenytoin so your phenytoin or phosphenytoin these ones have been shown to cause something called fetal hydrantonin syndrome Highland tones High Denton syndrome so fetal High Dan toen syndrome

is a really really big one so don't forget that one and the last one is carbamazepine so carbamazepine is going to cause things like cleft lip and a cleft palate and these are really really sad things so you really want to be able to pick this up and make sure that you don't miss this whenever a patient is pregnant I wouldn't want to put a patient who has generalized on a chronic seizures on valproide who's potentially pregnant are looking to be of childbearing age and looking to get pregnant they have this high risk of neural

tube defects generally Sonic's these are the status epileptic because of the patient I wouldn't want to give them phenotone phosphatidone focal seizures I wouldn't want to give carbazepine all right couple other things to remember that may come up on the exam because they love to ask these questions because they're always usually the likely thing to be questioned on is other specific big high yield Buzz term adrs valproate specifically watch out for pancreatitis so inflammation of the pancreas is pretty common also it may drop the playlist so thrombocytopenia but pancreatitis is the big one carbamazepine it

may produce siadh which may cause the patient to have a hyponatremia so watch out for that with carbazepine and oxcarbazepine phenytoin phosphenotonin really weird one but it's important to remember it can cause a very significant thickening and increased production of the gingiva which is called gingival hyperplasia that's another big one and if you stop that use it we'll actually regress back to the normal position vygabitrine vigabitrine vision loss is a big one and then last but not least my friends is to Pyramid this one has been shown to cause things like metabolic acidosis metabolic acidosis

as well as kidney stones and to some degree relatively rare but glaucoma as well but I really want you to remember metabolic acidosis and then again kidney stones because they're likely going to be the most common causes that you can see without drug all right my friends that covers the Whiteboard section but let's quickly do some questions to see if we can test your knowledge and understand everything we went over all right my friends so let's do some questions here so first one we have a nine-year-old boy sent for a neuro evaluation because of episodes

of apparent inattention right so over the past year he's been having these kind of episodes where he develops a kind of a blank look in his face his eyes blink for about 15 seconds and then he resumes his previous activity like nothing ever happened which best describes this type of seizure well remember there's focal seizures right there's generalized seizures within the generalized category there is tonic clonic tonic clonic there's atonic myoclonic and then absence remember I told you that this is tonic clonic this is tonic this is clonic atonic as you go limp myoclonic is

rhythmic kind of jerking quick movement and then absence is you stare out so this would fit in absence seizure right so that's classic and young individuals um who kind of have these blank stares in class pretty classic all right child is experiencing absence users that interrupt his ability to pay attention during school which is the most appropriate therapy for this patient most common answer is that those socks Vibes remember absence seizures you can use things like valpro you can use Lamotrigine or you can use ethosoxamide generally in children ethosoxamine is preferred okay but other options

include about protein lamotrigine so what drug is most useful for the treatment of absence teachers again it could be Lamotrigine valproate or ethosoxamide ethosoxide is prefer for children but you could also use something like in this category is their valpro 8 no is there Lamotrigine yes so it's got to be Lamotrigine all right 25 year old woman would generalize seizures as well controlled on valpro8 okay so she's taking this for generalized seizures likely tonic clonic she indicates that she is interested in becoming pregnant in the next year with respect to her anti-seizure medication which the

volume should be considered remember valproate carbamazepine and phenotone phosphonatone have uh teratogenic effects so I need to avoid those drugs at all costs so I would just discontinue her off of that and if I could switch to something switch to something that has less type of you know toxic effects and so leave her under current therapy no switch to the motor Gene there's no teratogenic effect of Motrin add a second anti-seizure no because then she's still on valpro 8 or decrease her valproduce no just get rid of it so best answer would be switched to

another one that's not teratogenic such as Lamotrigine okay so that'd be the best option here our patient focal seizures has best been has been treated for six months with carbamazepine it's great for focal seizures that as well as oxcarbazepine are going to be good ones in this particular situation levitarazatam Lamotrigine to Pyramid to some degree phenytone phosphenotonin not so great um but valproates also kind of okay in this particular scenario but generally Lamotrigine to pyramate levitarazatam oxcarbazepine and carbamazepine are the preferable ones so with that being said having some breakthrough seizures on a more frequent

basis you're considering adding a second drug to the anti-seizure regimen which of the following drugs is least likely to have a pharmaceutic interaction with carbonazepine so this is basically saying which one of these drugs has less kind of cytochrome p450 interactions in comparison to others and the one that I think is really really important to remember that really has almost no drug interactions because it's primarily renally excreted it's levitaraz attempt so levitarazatam is going to be one of the best drugs with less drug drug interactions as well as very little adverse effects 75 year old

woman had a stroke approximately one month ago she was continuing to have small focal seizures so again focal seizures oxcarbazepine carbamazepine levitarazatam is a potential opsin option here um as well as Lamotrigine to Pyramid those are all options and then phenobarbital and neonase remember phenobabies tall but in the situation they can have small focal seizures which she fails to respond appropriately while talking which is the most appropriate treatment for this individual so for a focal seizure you could consider oxcarbazepine phenytoin levitarazatam or phenobarbital between these phenobarbital is not a good option okay that's usually going

to be for more patients like remember neonates is the preferable agents or status epilepticus refractory phenotone's not super great um for patients who have again focal seizure so it leaves oxcarbazatine and levitarazatam these are both great agents so I think when it comes down to it I would consider levitarazatam to be the preferable agent just because of age all right so levitarazatamine is going to have way little adverse effects so I'd go with that one being the option I'd love to razzatam but again ice-carbazepine is not a bad option you could also consider that one

all right my friends that covers these questions here regarding the anti-seizure or drugs for epilepsy medications I hope it made sense so but you guys enjoyed it as always until next time [Music]