Anti-Epileptic Medications: Pharmacology of Seizures, Epilepsy & Status Epilepticus

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

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