what is going on wonderful people it's medicosis perfectus where medicine makes perfect sense welcome back to my pharmacology playlist today we'll talk about the medications used to treat seizure or epilepsy AKA anti-epileptic medications what's the difference between seizure epilepsy and convulsion today we'll find out the difference among these three we'll talk about nerve transmission and ion channels we'll talk about how to manage status epilepticus as well as how to manage seizure during pregnancy so click the like button click the Subscribe button and let's get started this video is part of my pharmacology playlist in which
you'll find any pharmacology topic you can imagine this video was made possible because of the great support from Maria she requested that I make a video on seizure medication so there you have it please please please say thank you to Maria in the comments thank you so much in advance and thank you Maria for supporting my my channel so what are we going to talk about today what is seizure what is convulsion what is epilepsy what is status epilepticus it's an emergency situation by the way we'll learn about synapses neurotransmitters and ions and ion channels
that are implicated in seizures we'll review some topics from pharmaco Kinetics remember that pharmacokinetics is all about absorption distribution metabolism and excretion metabolism is by the liver excretion or elimination is by your kidneys or your gut then we'll talk about these seizure medications as well as a quick review so if you want to understand what this is all about get a piece of paper and draw this with me here is the neuron what do we have we have a cell body here and we have an axons here amazing now what remember depolarization what was depolarization
depolarization was when something positive such as sodium enters into the neuron when the positive enters in the inside becomes more positive and this is called depolarization which is activation amazing but what if a positive left the neuron and went outside such as potassium leaving the chat as the positive leaves I get the exact opposite of activation which is inactivation instead of calling this depolarization we'll call this repolarization or hyperpolarization which means inactivation okay if a positive enters it is activation but what if a negative such as chlorine enters into the neurone oh since the positive
entry is activation therefore the negative entry will be inactivation so when sodium comes in this is activation or depolarization when chlorine comes in this is hyperpolarization inactivation when potassium leaves also hyperpolarization or inactivation you will learn soon that Gaba will open close chlorine channels so Gaba does what inactivation or hyperpolarization Gaba is inhibitory when the inside of the membran is negative we are inactive but when positive rushes in we become active some definitions please what is epilepsy epilepsy has to be chronic recurrent neurological disorders sensory problems maybe Plus Motor problems maybe with loss of consciousness
normally my brain activity should be a asynchronous nonsynchronous however a prolonged synchronous depolarization is what we call seizure and if I have it for a long time recurrent attack now we call it epilepsy so epilepsy is a chronic seizure dis order what causes seizure well we do not know also everything can cause seizure problems in metabolism glucose issues can lead to seizure electrolytes issue sodium high sodium low can cause seizures magnesium iium is high magnesium is low can also cause seizures infections can do it trauma can do it toxins can do it it is incurable
but controllable so seizure is a very big umbrella like you see here if I have chronic recurrent attacks of seizures we'll call this epilepsy chronic recurrent unprovoked now just because it is called seizure doesn't necessarily have to be convulsion sometimes I'm not shaking at all sometimes I'm if I am shaking we call this convence such as gr mal seizure but if I'm not shaking this is pity mal seizure what do you mean by shaking what do you mean by convulsions intense attacks of involuntary repetitive muscular contractions if they last more than 5 minutes and the
convulsions do not stop this is called status epilepticus and this is now an emergency what's the definition of seizure which is the broad umbrella parois electrical discharges of the brain sometimes people have loss of consciousness sometimes they do not sometimes I have alteration of perception maybe with impaired psychic function and maybe with loss of sensation what's the definition of epilepsy this is recurrent chronic unprovoked seizures what's the definition of status epilepticus convulsion for more than 5 minutes this is a life-threatening situation which requires immediate medical attention and of course the medications that we give in
an emergency are not going to be oral medications but instead they will be intravenous injections so seizure is the big broad umbrella term 2/3 of the seizures are convulsive seizures and only 1/3 is non-convulsive seizure seizures could be classified into focal seizures and generalized seizures what do you mean by focal seizure I mean it affects only one focus of the brain one part of the brain and it will involve only one part of the body for example just my right arm is shaking because the problem is in the part of the brain that controls my
right arm for example but generalized seizure means all over the body because all of the brain is involved focal or partial seizures are divided into two subtypes simple seizures and complex seizures what do you mean by simple I mean we have spared Consciousness I did not lose Consciousness but with complex seizures we have loss of consciousness abbreviated as L LOL sometimes seizures have Aura which is a prodrome of several kinds of symptoms could be sensory symptoms autonomic symptoms psychiatric symptoms or motor symptoms some auras or prodromes are visual such as flashing lights in front of
my eye then the seizure will happen or hearing a certain sound or a certain noise then seizure takes place or smelling a certain smell and then seizure happens or having a weird sense of taste then seizure takes place how about generalized seizures which involve all of the body and all of the brain here we'll have loss of consciousness which means they are complex some of them have shaking all over the body tonic clonic seizures in French gr M seizures some of them are all over the body the entire brain is involved however I am not
shaking and these are called absance seizure or pyol seizure then we have other types such as tonic seizures clonic seizures myoclonic or atonic I.E flaccid seizure so there you have it the definitions of seizures convulsion status epilepticus gral versus pmal as well as epilepsy now which site well partial seizure or focal seizure will involve one Focus but generalized seizures will involve the entire brain and you got to understand and know the different functions of the different parts of the brain for example the frontal L controls excusion movement thinking judgment Etc parietal lobe sensory remember my
imaginary line just like this in front is motor behind is sensory so in the parietal lobe we have what we have Sensations like the sense of touch the sense of pain temperature Etc the occipital lobe is for vision the temporal lobe is for hearing and memory the cerebellum is for balance and equilibrium as for the brain stem especially the medulla it has four famous centers heart and lungs get it in get it out Cardiovascular Center respiratory Center swallowing Center and vomiting Center heart and lungs get it in get it out what causes seizures well we
do not know also anything can cause seizure esia can do it hypoxia can do it Hemorrhage can do it inflammation can do it ector SK necturus jaundice and neonates can do it low glucose can do it high glucose might do it as well hypocalcemia hypomagnesemia hypo or hyper nmia as well as other issues and that's why we need to control and correct the underlying pathology if it exists and that's why we need CBC CMP electrolytes to find these abnormalities EEG will be very important why do seizures continue why do they prolong who sustains seizure re-entry
circuits in the brain re-entry of excitatory impulse creating a feedback loop again and again and again so the seizure stays with me conversely synaptic fatigue can reduce seizures transmission of impulses through the nerve synapse like this can get tired over time synaptic fatigue is one of the characteristics of synaptic physiology that's why it ends when it does so we've just finished the first bullet point now let's talk about status epilepticus which is an emergency situation what was the old definition the old definition was continuous unremitting unresolving continuous seizures for more than 30 minutes that was
the old definition but if you wait for 30 minutes to decide whether status epilepticus or not the patient would be toast that's why the definition was changed into for more than 5 minutes now when you change the definition like this when you lower the cut off value what's going to happen to the incidence of status epilepticus the incidence will increase and some lovely news journalists and fear mongers will claim there is an epidemic of status epilepticus in the country well of course when you change the definition from more than 30 minutes to more than 5
minutes more people will be counted within your new definition why is math so hard status epilepticus is an emergency neuronal cell death can occur and long-term neurological sequel May ensue that's why we need to treat the patient quickly with intravenous medications not oral medications because intravenous medications have higher bioavailability the bioavailability of intravenous medications is set to be very close to 100% so what should I do you give benzodiazapines like lorazapam or diazapam benzodiazapines are stives and hypnotics then what then you give phenin or phosphino phosphinine is a pro drug that will be metabol ized
into phenin what if my patient is not responding yet then give me phenobarbitol what if the patient is not responding yet now it's time to take it to the next level and give a general anesthetic such as propofol or theopen thiopental like phenobarbital is a barbiturate remember that toxins can lead to seizure remember that vitamin B1 deficiency can lead to seizure so it's a good idea to give thamin or vitamin B1 because sometimes the patient is an alcoholic and if you give glucose to an alcoholic patient without giving thamin you will kill the patient now
let's talk about some neurophysiology which is the basis to understand pharmacology remember again sodium enters this is activation when chlorine enters as in the gabet channel this is inactivation when potassium leaves the chat this is inactivation as well so in epilepsy or seizures what's happening is that the neuron is super duper hyper excitable so how should we treat decrease the excitation decrease the activation block those sodium channels so that sodium cannot enter or enhance the Gaba so that the Gaba can let the chlorine in and cause inactivation and calm my excited brain down there is
also another way to do it which is to inhibit calcium channels oh why should I inhibit calcium cuz remember that calcium is the thing that releases the neurotransmitter from the vesicle this is just one type of calcium channel Illustrated here reality is way more complex than this but you get the concept so I either block the sodium channels block the calcium channels or enhance the Gaba let's talk about neurotransmitters you know glutamate and aspartate these are excitatory neurotransmitters but Gaba and glycine are inhibitory neurotransmitters so how do I treat epilepsy get rid of glutamate and
enhance the Gaba get rid of the excitatory and boost the inhibitory to inhibit I.E calm down my excited brain see pharmacology makes so much sense once we understand what the flip we're talking about so the pharmacology hinges around blocking sodium channels blocking calcium channels or boosting Gaba there are many different types of Gaba such as Gaba a Gaba B and Gaba C medications that work on Gaba a include benzodiazapines and barbiturates both of them can be used to treat seizures all of the following drugs act on Gaba which is an inhibitory neurotransmitter benzodiazapines do it
that's why they are sedatives and hypnotics they C you down nonb diazines barbiturates propol inhale General anesthetics and more that's why these medications the sedatives and hypnotics can be used for Sedation hypnosis decrease anxiety decrease seizure decrease memory relax your muscles and knock you unconscious because they do what they boost Gaba and Gaba is what an inhibitory neurotransmitter here is Gaba when you enhance Gaba the chloride Channel opens chloride delves into the neuron I.E chloride influx causing what when the negative enters into the neuron it is hyperpolarization or inactivation medications that act on Gab a
include benzodiazapines and barbiturates but what's the difference benzodiazapines increase the frequency of chloride Channel opening so they open more often leading more chloride to enter into the neuron conversely barbituates increase not the frequency but the duration I.E the chloride channel will remain open for a longer period of time so both Bodines and Bar bit rates are sedatives and hypnotics the Bodines increase the frequency of opening of the chloride channels but verbit rates increase the duration of opening either way you're going to lead more chloride into the neuron causing inactivation and hopefully treating the seizure how
do I remember which is which for barbiturates it's duration so just say barbiturates Barb durate duration and now onto pharmaco kinetics let's review the kinetics of pharmacology if you want a more detailed discussion on pharmaco kinetics check out my general pharmacology course on my website medicosis per fiction.com pharmacokinetics is basically what your body does to the drug but for Maco Dynamics is the opposite it's what the drug does to your body for Maco kinetics what my body does to the drug it's basically absorption distribution metabolism and elimination or excretion so is a d m e
or you can say Adam spelled funny there are many roads of administration you can give the drug orally intravenously intramuscularly Etc intravenous will give you the highest bioavailability which is around 100% so intravenous medications have high bioavailability the highest that you can imagine conversely if I taking oral medication what's going to happen is after it leaves my gut and goes to the blood it's going to reach the vicinity of the portal circulation and it's going to go to the liver and the liver will metabolize it first before sending it to the bloodstream or the peripheral
circulation and this is called what the first pass hepatic effect or first pass metabolism by the liver then it will send it to the blood and then eventually it will come back to the liver to be metabolized again and that's why if I have an emergency like status epilepticus we give intravenous medications not oral medications because they have high bioavailability what's the definition of bioavailability the relative amount of the drug that reaches the systemic circulation here is the story of phaco kinetics in just one slide suppose that you injected me with a drug so the
syringe is now inside my vein and the drug will be injected to my veins to my circulation so it did not cross any membrane because you already put it here yourself so there is no Crossing of membranes which means there is no absorption however if you give me an oral medication it has to leave my gut and go to the blood and in order to do this you have to cross a membrane when you cross a membrane it is called absorption okay whatever whether I took it intravenously or orally or intramuscularly eventually it's going to
reach the blood then what inside the blood some of the drug or a part of it a portion of it will be bound to Albin another portion will be free in the blood which one is physiologically and pharmacologically active the free Unbound form is active however the one that is bound to albumin is inactive and then what when this albumin carries the drug towards the cell then it will leave that drug hey you can leave me now and go to the cell and when the drug goes to the peripheral tissue it is called distribution then
after it gets distributed to tissue it's going to take its effect it's going to cause me or give me the therapeutic effect and and the side effects you cannot have one without the other it's like two faces of the same coin the trick is to try to maximize the therapeutic effects the desired effects while reducing the side effects but remember that when the drug leaves the albumin and leaves the blood and goes to the tissue that tissue could be what could be liver metabolism or kidney elimination the liver does many things one of them is
to make albumin which is the protein that will carry a portion of many drugs in the blood it also secretes a waste product known as Ura so now my blood has Albin and Ura what's going to happen they will reach the kidney eventually Ura is the bad guy so let's get rid of it this is called elimination or excretion but albumin is the good guy albumin should not be urinated out albumin should stay in the blood that's a good kidney it is a kidney that does not filter the albumen out but what if I have
kidney disease oh oh my kidney is screwed so the albumin will be lost in the urine and I will get albuminuria oh if there is more albumin in your urine what's going to happen to the level of albumin in your blood it will be low which means that kidney disease can lead to hypoalbuminemia or low albumin in the blood what else can lead to hypoalbuminemia how about a problem in the factory liver disease can also lead to hypoalbuminemia so whether I have liver disease or kidney disease I can get hypo albuminemia what's going to happen
to the albumin level in my blood it decreases which means what I'll have less taxi cabs to carry the medications around so the medication will be unable to bind to Albin because I have less Albin so the drug will be forced to float freely into the bloodstream and this is more active and therefore more toxic so hypo albinia can lead to what increased drug toxicity and that's why if you know that your patient has liver disease or kidney disease you should adjust the dose I.E reduce the dose of the medication and give that patient a
lower dose than his counter part with no liver or kidney disease pharmacokinetics is a DME absorption distribution metabolism excretion let's talk about metabolism I.E biotransformation let's transform the drug from one form to another it is mainly done in the liver why do we metabolize drugs to convert them from something less water soluble into something more water soluble send that more water soluble thing to the kidney to get eliminated in stage four metabolism of drugs in the liver could convert something active into something inactive or something inactive to something active such as pro drug example phosphinito
becoming photoin or converting active to something more active or converting active to something toxic one of the enzyme systems in the liver is called p450 and it's used for huged metabolism it's also known as liver microsomal enzymes and as you know enzymes are proteins these kinds of proteins contain he some medications induce the p450 enzyme system which means the liver will met abize other medications faster leaving less of the medication in the circulation conversely other medications inhibit the p450 system when I inhibit metabolism of other drugs what's going to happen the drug will stay longer
in the plasma causing more toxicities famous examples of p450 inducers are photoin carbamazapine rampin barbiturates chronic alcohol NAA pain aavin glucorticoids St John's wart and gravin as for the p450 Inhibitors we have quinidine we have SEO we have ionized grapefruit juice aryin acute alcohol use indinavir cadine sulfonamides ssris calcium channel blockers and ketonal I try to divide them into antifungals so here's an antifungal that induces and here's an antifungal that inhibits here's an S so St John's versus Sul pides here is anti-immune Ulcer here is an anti-hiv medication anti-v medication here is chronic alcohol versus
acute alcohol here is a medication for tuberculosis another medication for tuberculosis since today we focus on anti-epileptics please remember that photoin carbamazapine and barbiturates are p450 inducers phac kinetics is all about absorption distribution metabolism elimination let's talk about elimination or excretion let's get rid of the drug usually done by the kidney but could also be lost in the stool some medications are excreted via bile what is elimination halflife it's the time needed to eliminate 50% of a given amount of a drug or the time needed to reduce the plasma level of a drug to 50%
of its original value for example let's say that you gave me 100 mg of drug and then we waited 2 hours after 2 hours only 50 mg of that drug is left in my system what's the half life I.E how long did I have to wait before I get half of the amount answer the half life is 2 hours in this case how about here look at those 50 Mig wait another 2 hours they become 25 what's the half life here 2 hours so when you give me the medication I start up here this is
my plasma concentration and look what happens what happens as I eliminate the drug its concentration decreases over time there are two main patterns of elimination there is zero order elimination and first order elimination the former is known as saturation kinetics the latter is known as exponential kinetics here is a linear relationship as you see but this one is an exponential or nonlinear relationship linear is also known as arithmetic and the exponential is also known as is geometrical saving your money under the mattress year after year will make it grow linearly but investing money year over-year
and earning compound interest on top of compound interest will make your wealth grow exponentially donating $10 every year is a linear relationship that's a constant amount being donated every year but donating half of your wealth every year is an exponential relationship because you are donating a constant fraction not a constant amount every single year so when a constant amount is being lost this is called zero order elimination but when a constant fraction percentage is being lost this is first order elimination how do I remember which is which the one that has fraction with an FR
is the first order elimination f r so constant amount is being lost per year is zero order constant fraction or percentage being lost is first order if I am taking a medication would I prefer that this medication follows zero order elimination or first order elimination of course I will prefer the first order elimination because a constant percentage is being eliminated per unit time but with zero order elimination a constant amount is being eliminated per unit time which means if I mistakenly took an overdose the body doesn't care the body will still get rid of a
constant amount per unit time so if I take a low dose same amount is being eliminated if I take a very large dose the same amount is being eliminated so you can imagine that this is why toxicity of a drug in zero order elimination is more dangerous than that in a first order elimination thankfully most drugs follow first order elimination but the there are some medications that follow zero order elimination such as aspin ethanol and phenin especially at high doses phenin is a famous anti-seizure medication but we got to be very careful with the dose
because it can follow zero order elimination and we will talk about the side effects of photoin very soon next we have first order elimination where a constant fraction of the medication is being eliminated per unit time so do I prefer this of course course because if I take a low dose let's say the body will get rid of half of it in the first day but if I take a high dose the body will still get rid of half of it in the first day which is amazing which decreases the risk of toxicity most drugs
follow first order elimination except if given in very high concentrations because if you give them in very high concentrations you will saturate the receptor or the carrier protein and you will shift from first order to zero order remember first order a constant fraction is being eliminated and this is the exponential decay so can you look at these two graphs let's call this one graph a and this one graph B which one is zero order and which one is first order please pause and try to answer this yourself the linear Decay is zero order elimination but
the exponential decay is first order when there is a constant fraction it's first order now let's actually talk talk about the anti-epileptic medications some general rules on anti-epileptic medications gradual dose titration is recommended so that I do not overdose unexpectedly many patients prefer sustained release of the medications which also will give me a steady state concentration without being below the threshold or above the threshold gab a Penton has very slow GI absorption please remember that many of these anti-epileptic drugs are excreted or eliminated by the kidney so if the patient has kidney disease you need
to adjust the doses I.E lower the doses of the following medications these are the ones excreted by the kidney Gabapentin pregabalin litam vigabatrin and zonisamide as for the other anti-epileptic medications you will need to adjust the dose for patients with liver disease so how do I remember it I remember the kidney ones and everything else is liver so what are the kidney ones recall that the kidney can remind me of GFR oh that's true GFR loves but we will write loves this way okay who's the GFR the G is Gabapentin okay how about the F
FR well that's pre gabblin so it became GPR r instead of GFR okay what is loves LV z l is Liv acetam V is VAB vatran and Z is zamite and there you have it everything else is liver many of these anti-epileptic drugs have p450 interaction many of them induce the p450 enzyme system except great love G LV who's the G Gaba Penton again who's the L Liam again and who's the V vabon one more time you know what we can change this pneumonic so who excr renally great love and then easy peasy peasy means
p and Z so great love that's the G LV great great love easy peasy p and Z great love easy peasy means kidney anything else is liver great love means I am not going to interact with p450 I'm not going to induce it I'm not going to inhibit it many medications and medicine love to bind to plasma proteins especially albumin in my bloodstream so if this is my blood vessel right here and I have albumin inside of it many medications will hug the albumin strongly and these include fenin pric acid and carbamazapine these are three
anti-epileptic medications and I will give you three non anti-epileptic medications include thyroxin silicate and phenazone which is not used today all of these medications love to hug alamin strongly which means they can be displaced by another medication that also loves to bind albumin strongly so these medications can kick others from the AL Albin or they can get kicked off the albumin and if they get kicked off the Albin what's going to happen they will go to the plasma they will be freely floating and when they are free they are active increasing their toxicity next don't
forget that liver disease or kidney disease can give me hypo albuminemia and if there is no Albin to hug the drug the rest of the drug will go to freely float in the plasma raising the plasma drug concentration increasing the desired effects and of course increasing the side effects increasing the toxicity now let's give a hypothetical example suppose that the half life of the drug is 10 hours okay so every 10 hours the concentration of the drug in my plasma decreases by half how should I give the drug to the patient in a way in
a pattern that makes the drug within the range of steady state concentration and not fall below the sub threshold or the sub therapeutic level so here's how you you do it you give a dose every half of the half life what does that mean if the half life of the drug is 10 you should give a dose every 5 hours so that every time the drug tries to decrease and get eliminate completely you add another dose tries to get eliminated you add another dose tries to get eliminated you add another dose to prevent the drug
from falling beneath the sub therapeutic level here's a lovely summary of the anti-epileptic drugs drugs that inhibit voltage gated sodium Channel include photoin carbamazapine valproic acid or valproate to parate and the mogene note that phenin velate and lamotrin inhibit not just the sodium Channel but also the calcium channel s for carbamazapine it inhibits sodium channels only then medications that inhibit the calcium channels include ethos oxamide and vate again lamotrin could be also written here because lamotrin inh inhibits both sodium and calcium channels ethos oxamide inhibits only the calcium channels which type of calcium channels the
T type in the thalamus among other areas of the brain next the Gaba enhancers include remember the barbituates and the benzodiazapines barbituates will increase the duration of chloride Channel opening the benzo diazines will increase the frequency of the chloride Channel opening next we have medications that inhibit Gaba trans m& which is an enzyme that breaks down Gaba so when I break the breaker I will end up having more Gaba oh boosting Gaba yeah who does that V pro8 can do it and V gabrin I mean look at the name it has Gaba in it of
course it boosts Gaba another medication is called T gabin oh look at the Gaba in the name it inhibits the reuptake of Gaba so if this is my neuron like here and then this is the post synaptic neuron and then I have the receptor for Gaba Gaba is here I want Gaba to bind to its receptor so I will inhibit the reuptake of Gaba so that Gaba does not enter the neuron again and instead of going to the pre synaptic neuron it will stay on the post synaptic neuron causing its Gaba effect and Gaba is
inhibitory that's how you treat seizures you see this to pamade it is anti-a glutamate receptor glutamate has two types of receptors ampa and nmda who's going to inhibit ampa toate who's going to inhibit nmda felbamate remember that glutamate is an excitatory neurotransmitter when you inhibit the excitatory you become inhibitory I.E you inhibit the seizure excitation let's start by phenin which is a hent toin or sodium hyen toin if you're picky when should we use it what are the indications you can use it for focal or partial seizure as well as generalized tonic clonic seizure so
partial as well as generalized can we use it for status epilepticus yes because we used phenin or it's prod drug fos phenin this medication is available oral as well as intravenous of course intravenous has higher bioavailability does fenin cause excessive sedation not usually how does it work well it inhibits voltage gated sodium channels that's the most important mechanism and then if you want to add inhibiting calcium channels that's also okay it keeps my sodium channels in the inactivated State and when sodium is not rushing in I am decreasing the conduction of action potential I.E decreasing
the seizures remember that many seizure medications can be used to treat cardiac arrhythmias because what is arhythmia but a seizure in my heart what is seizure but an arhythmia of my brain that was deep this quote is not mine is it water soluble not really therefore what therefore I have a variable absorption time in the GI usually slow absorption in the gastrointestinal tract the initial dose for adults is usually between 3 and 4 Mig per kilogram of body weight try not to exceed 500 mg because that's too much and remember when you give too much
what's going to happen zero order elimination which is dangerous because at a certain height dose you will saturate all of your receptors I.E all of the hydroxy enzymes in my liver and after that point just adding a little dose of photoin will lead to a huge increase in the plasma concentration and therefore toxicity of photoin so be very careful so I should not exceed 500 mg oral dose how about intravenous you should not exceed 5 mg per minute and in the Pediatric population you should not exceed 1 to 3 mg per kilogram what if I
gave too much well you go to zero order elimination which is dangerous how dangerous don't forget that anti-seizure medications are also anti- arhythmic medications so I can get what I can get Brady cardia and hypotension and Brady arhythmia okay what do you want my plasma concentration of photoin to be I want it to be between 10 and 20 microG per ml is it used for anything else but seizure yes you can use it for arhythmia especially dejin induced cardiac arhythmia 90% of photoin likes to bind albumin which means I got to be very careful in
patients with liver disease who have low albumin in patients with kidney disease who have low albumin and in neonates at low concentrations less than 10 microgr per ml it follows first order but if you give too much such as above 10 10 microG per ml you switch to zero order and you get this dramatic increase in plasma photoin concentration what are the side effects it is toxic to the liver can lead to hepatotoxicity especially at high dose of course phonin is given to trade seizure which is hyper excitability so that's why it causes CNS depression
instead high doses can lead to heroism gingival hyperplasia important lupus like reaction or drug induced lupus allergic such as rash and pseudolymphoma which is not a true lymphoma there is no cancer just swollen lymph nodes with fever and rash photoin can interfere with the absorption of vitamin B9 which is folate this can lead to megaloblastic anemia photoin can also interfere with vitamin D leading to rickets in children or osteum malaia in adults if I overdose I can get coma cardiovascular collapse with hypotension and bradicardia as well as respiratory depression depression photoin is not okay during
pregnancy it can be dangerous causing the fetal hyen toin syndrome Canino lead to nagas Sure Axia yeah diplopia vertigo drowsiness yes indeed can it cause peripheral neuropathy sure here is your normal sodium Channel it is resting then it opens then it closes then it rests etc etc what finin does is that it comes to the sodium Channel and keeps it in the close Ed inactive State that's how it treats the seizure and that's how it causes CNS depression side effects of phenone the P suo lymphoma the age hepatotoxicity gum hyperplasia or gingival hyperplasia heroism and
Fetal hent toin syndrome the E reminds me of vitamin B9 which is folate and vitamin D then I have the O zero order elimination when I exceed 10 microG per ML and the N is nice tagas if you want to learn more about fatal hyen toin syndrome I've talked about it in a separate video that you will find in my pharmacology playlist don't forget that fos phenin is a pro drug that can later be converted to phenin phos phenone is given by intravenous infusion to treat the emergency situation known as status epilepticus do we love
phosphinito yes we love fosin because it has less side effects than phenin here's a list of medications that can lead to gingival hyperplasia this is not a comprehensive list but you need to remember feno in cyclosporin and calcium channel blocker anti-seizure anti-immune arhythmic next we have carbamazapine why do we use it it can treat partial or focal seizure it can treat tonic clonic generalized seizure it can treat status epilepticus it can even treat bipolar Mania trigeminal neur neuralgia and glosso faral neuralgia very important this medication is only available orally it has robust rapid absorption about
80% of carbamazapine is bound to albumin its elimination halflife ranges between 8 hours and 24 hours carbom amip Pine is weird it induces its own metabolism # autoinducer which can result in sudden reduction in its own plasma concentration which decreases its therapeutic effects so what should I do it requires increase in the dose in about 2 to 4 weeks what does it do it inhibits sodium channels what are the possible side effects hepatitis again with elevated liver enzymes CNS depression again don't forget that it's autoinducer it can lead to rarely a plastic anemia which is
not an anemia but pancytopenia low red blood cells low platelets and low white cells it can also lead to rash and Stevens Johnson syndrome which is a potentially fatal disease carbamazapine can also lead to a syndrome of inappropriate ADH secretion because at high concentration carbamazapine acts like ADH or anti- dtic hormone also known as Arginine V supress since caripan is a p450 inducer it will induce the metabolism of itself plus other medications carbamazapine induces the metabolism of valproic acid ethos oxamide corticosteroids anticho and even anti-coagulants because they use the p450 system conversely medications that inhibit
the p450 system will result in inhibition of the metabolism of carbom mopine and increase in the toxicity of carbamazapine such medications include cadine deltm Verapamil isid and erisin as we have discussed before carbamazapine can be teratogenic it causes cleft lip cleft pallet neural tube defects cardiac defects and bladder defects or urinary defect next we have Vel Pro weight it inhibits the sodium channels the T type calcium channels and it even inhibits gabat transaminase raising Gaba which is inhibitory to inhibit the seizures what kind of seizures all kinds of seizures it can treat partial seizures it
can treat generalized seizures whether the are tonic clonic or Epson gr M or p m it can even help us in status epilepticus when it comes to the partial seizures valproate is better at suppressing the convulsive partial seizures rather than the non-convulsive partial seizures valproate is absorbed quickly by giving it orally the peak plasma concentration is between 1 and 4 hours more than 80% of V pro8 loves to hug plasma proteins especially Albin the elimination half life is between 7 and 17 hours side effects of course if you know nothing just say nause your vomiting
diarrhea if you want to add another one zeria V proit can also lead to anorexia it can cause weight gain that's important pneumonic Val Pro weight with a V will make me overweight with a V it can lead to hepatotoxicity there is no shock there it can lead to pancreatitis CNS depression thrombocytopenia which raises or prolongs the bleeding time it is also teratogenic it can lead to neural tube defects and it can lead to alopecia or hair loss and when it damages the liver it can lead to hyper ammonemia increased ammonia in the blood but
the hyper ammonemia from V proit can happen even if the liver was not damaged another side effect IS F Tremors valproic acid can be eliminated as a ketone containing metabolite velate is capable of displacing phenin from the plasma protein binding site which means valproate will kick phenin off the Albin increasing the phenin side effects valproic acid can actually work as a p450 enzyme inhibitor not an inducer so all of the previous ones were inducers we talked about the carbamazapine the phenin and even barbiturates can induce the p450 system but not Vel pro8 V pro8 enough
is enough I'm going to inhibit the p450 system which slows down the metabolism of other medication such as phenin yet another mechanism by which Vel proit increases the toxicity of phenin velate can also raise the plasma concentration of phenobarbitol which is a barbiturate does v pro8 interfere with the action of oral contraceptive drugs no remember when we talked about anti-seizure medications the ones that inhibit the calcium channel they inhibit the T type IE transient type calcium channel in the thalamus to prevent the burst of thalamic activity and to prevent excitation classic example is ethos oxamide
ethos oxamide inhibits the T type calcium channels we use it mainly for epsons or p m which is a generalized seizure with no vence side effects CS depression yet again blood discaria so it can lead to anemia thrombocytopenia Etc and maybe maybe teratogenic but usually not as much as the previous ones glutamate and aspartate are excitatory but Gaba and glycine are inhibitory too much glutamate I get seizure too much Gaba I get no seizure therefore how do you treat seizure you either inhibit glutamate or boost Gaba Bingo how do I inhibit glutamate we'll talk about
some medications that are anti-glutamate but how do I induce Gaba we'll talk about some medications that boost Gaba some of them mimic Gaba some of them inhibit the re-uptake of Gaba and some of them inhibit the metabolizer of Gaba Gaba pentin pregabalin and vegab batrin are Gaba medications if you're PR Gaba we can use you to inhibit pain so they can manage pain to inhibit chronic pain neuropathic pain in diabetic people Etc but if we inhibit you so much what's going to happen weight gain due to decrease activity and decrease metabolism and it's not just
Gaba pentin pregabalin and V gabrin because we also have t gabin look at the Gaba in the name which inhibits the re-uptake of Gaba and you shall not forget that phenobarbitol lorazapam diazapam clobazam are sedatives and hypnotics how did they do this barbiturate increase the duration of chloride Channel opening but the benzos increase the frequency of chloride Channel opening and the chloride channel is part of the Gaba so we either boost the Gaba or inhibit the glutamate let's inhibit the glutamate we have three medications lamotrin Topiramate and felbamate Topiramate inhibits the ampa glutamate receptor filate
inhibits the nmda receptor how do I remember which is which look at the T with Thea together this is Tampa which is a city in Florida so it is Tampa and therefore the other one is the other one we are anti-glutamate we are anti- exitation therefore you can use us to treat seizure bipolar migraine Etc side effects Lam motogen is nasty it can lead to rash Stevens Johnson syndrome which is potentially fatal and it's also teratogenic and lead to cleft flip and cleft pallet when you inhibit excitation what do you get oh I get inhibition
I get sedation I get obesity as for felbamate it can lead to a plastic anemia which is a misnomer it's not just anemia it's anemia leucopenia and thrombocytopenia so a better term is a plastic pan cytopenia and there you go here is a summary of anti-epileptic drugs please pause and review epilepsy during pregnancy first of all there is no such thing as the best medication for seizure during pregnancy there is no the best medication it's all about tradeoffs balancing the risk with the benefit hey if I have an epilepsy or a seizure disorder is this
a contraindication to getting pregnant no pregnancy and seizure if I'm taking any of the anti-seizure medications they can lead to what decrease folage so folage supplementation is a must at a higher dose than the other pregnant women with no epilepsy why is this because many anti-epileptic drugs cause folate deficiency so what should I do take a medication that controls the seizures if we can get the seizure under under control with just one medication I.E monotherapy that's amazing not just that we will try to stay on the lowest possible dose which anti-seizure medication is the most
cogenic Val proit is which ones have high risk of fetal malformation photoin carbamazapine and to pomate remember that many anti-epileptic drugs induce the p450 boosting the metabolism of oral contraceptive pills which decreases the efficacy of oral contraceptives so if I'm taking let's say photoin and an oral contraceptive pel well I can get pregnant pregnant even after taking the pel yeah because the pill is being destroyed by photoin which boosts the metabolism of the oral contraceptive pill almost all of the anti-epileptic medications do it except Vel proit Vel Pro is not an inducer of the p450
system during pregnancy the clearance of lamotrin increases so if I decide to take lamotrin while pregnant I need to increase the dose of lrene what if I have convulsion during pregnancy what should we do right now bipin intravenously lorazapam for example should I give magnesium sulfate no magnesium sulfate is for eclampsia and not for the acute management of seizure during pregnancy are anti-epileptic medications contraindicated during breast feeding no they are not don't forget that 90% of pregnant women with epilepsy will have an absolutely normal pregnancy so let's recap we're trying to use monotherapy during pregnancy
we'll taper the dose to the lowest possible dose if the patient is seizure free for the last 2 to 5 years we try to completely withdraw the drug altogether but we only do so 6 to 12 months before conception we need to give folate at high do and we need to order maternal alphaet protein regularly during pregnancy to check for the presence of neural tube defects what's the medication that we use to treat galonic clonic generalized seizure you can use phenin carbamazapine vate barbiturate to pomate or lrene how about the p m or abson seizure
you can use ethos oxamide valproate or lrene how about partial or focal seizures you can use caropine phenin loten or to pyamid how about status epilepticus you start with loram diam you can add phenin or fosin if the patient is not responding add phenobarbitol if the patient is not responding switch to general anesthetic like propofol or thiopental theopen is also a barbituate like pheno barbital and here is the management of stus epilepticus once again this is very important for your exam and there you go the best chart for anti-seizure medications of all time today we'll
learn about seizure convulsions epilepsy we'll learn about status epilepticus we learned about neurophysiology for Maco kinetics the anti-epileptic medications and the summary table if if you want more pharmacology in your life I have the complete pharmacology set on my website medicosis per fiction.com such as my antibotics course my cardiac pharmacology course my neuro pharmacology course and every pharmacology course you can imagine if you want to learn about ischemic stroke hemorrhagic stroke angina myocardial infarction arhythmia ards and much more download my emergency medicine high yields course at medicosis per fiction.com there are more than 300 premium
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