Drug Mechanisms, Indications & Side Effects: Simplified with Mnemonics
1. Valproate (Valproic Acid)
Mechanism
- Inhibits voltage-gated sodium channels (decreases excitation)
- Increases GABA activity (increases inhibition)
Indication
- First-line for generalized seizures (tonic-clonic, partial), the default "go-to" when no specific seizure type is mentioned.
Main Adverse Effects (ADRs)
- Anemia, Hepatotoxicity, Pancreatitis, Spina bifida (neural tube defect)
Mnemonic: Think "All-Pro" (from Val-pro-ate).
- A = Anemia
- L = Liver (hepatotoxicity)
- P = Pancreatitis
- O (the hole/pouch) = Spina bifida (neural tube defect)
2. Phenytoin (Fenytoin)
Mechanism
- Inhibits voltage-gated sodium channels (only), no GABA effect.
Indication
- No single high-yield indication; used broadly for seizures.
Key Pharmacokinetics & ADRs
- Zero-order kinetics: drug eliminated at a constant rate regardless of dose.
- P450 inducer (increases metabolism of other drugs).
- Gingival hyperplasia (gum overgrowth).
- Fetal hydantoin syndrome (craniofacial abnormalities, limb defects, mental retardation).
Mnemonic: Think "Towin" (as in needing a tow truck).
- "If they don't salt the roads (voltage-gated salt channels), your car will need a towin."
- Snow hyperplasia = Gingival hyperplasia (snow = gum overgrowth).
- Zero order = No order on icy roads.
- P450 inducer = Inducing tow trucks to rescue cars.
- Fetal hydantoin syndrome = name ends in "-to win."
3. Ethosuximide
Mechanism
- Inhibits T-type calcium channels (just remember "calcium", that's the test answer).
Indication
- Absence seizures (high yield).
Main ADR
- Stevens-Johnson syndrome (severe rash).
Mnemonic: "Absence seizures suck" = Suc-cinimide (ethosux-imide).
Stevens-Johnson Mnemonic: The band "*NSYNC" members: Ethan (ethosuximide), Carl (carbamazepine), Larry (lamotrigine), Steven, Johnson. Ethan, Carl, and Larry can all cause Stevens-Johnson syndrome.
4. Carbamazepine
Mechanism
- Increases the refractory period of voltage-gated sodium channels (making them "rest" longer, blocking excitation).
Indication (Super High Yield)
- Trigeminal neuralgia, sharp, shooting, lancinating pain along V1/V2/V3 trigeminal nerve distribution.
Main ADR
- Stevens-Johnson syndrome (Carl from the *NSYNC mnemonic)
Mnemonic: "You chew carbs with your cheek." (Cheek = trigeminal nerve distribution; carbs = carbamazepine).
5. Lamotrigine
Mechanism (Unique: Dual Action)
- Inhibits voltage-gated sodium channels AND has activity at glutamate receptors.
- Only AED with this dual mechanism.
Main ADR
- Stevens-Johnson syndrome (Larry from the *NSYNC mnemonic)
Mnemonic: The seizure says, "Wow, you're attacking me at two receptors, that's lame-o" (la-mo-trigine).
6. Benzodiazepines vs. Barbiturates
Mechanism (Both: Increase GABA-A activity)
- Benzodiazepines: Increase frequency of chloride channel opening.
- Barbiturates: Increase duration of chloride channel opening.
Mnemonic: Barbiturate → "Bar-bi-dur-ate" → Dur-ation. (Then by elimination, benzos = frequency.)
Clinical Pearl
- Benzodiazepines are used as abortive therapy for active seizures.
7. Levetiracetam
Mechanism
- Unknown (but tested as "unknown mechanism" on exams).
Mnemonic: Imagine a magician making someone levitate. "How does he levitate? I don't know."
8. Tiagabine & Vigabatrin
Mechanism
- Both work on GABA (GABA reuptake inhibitor / GABA transaminase inhibitor).
Mnemonic: The drug names literally contain "GABA", Ti-gaba-ine, Vi-gaba-trin. Easy point.
9. Topiramate
Mechanism
- Inhibits voltage-gated sodium channels.
Mnemonic: Think of a top pirate on a pirate ship. Pirate ships sail on salt water → voltage-gated salt channels.
Summary: High-Yield Takeaway
- Stevens-Johnson syndrome: Remember Ethan (ethosuximide), Carl (carbamazepine), Larry (lamotrigine), three of the five friends.
- Carbamazepine → Trigeminal neuralgia.
- Ethosuximide → Absence seizures.
- Barbiturates = Duration; Benzos = Frequency at GABA-A.
- Valproate: Anemia, Liver, Pancreatitis, Spina bifida.
- Phenytoin: Zero-order kinetics + P450 inducer + Gingival hyperplasia + Fetal hydantoin.
- Levetiracetam: Unknown mechanism.
- Lamotrigine: Only dual mechanism (Na+ channels + glutamate).
For a deeper dive into how these drugs affect cardiac conduction (especially at toxic levels), see this Comprehensive Guide to Drug Effects on ECG Patterns and Cardiac Safety. To understand how NSAIDs (sometimes used in seizure-associated pain) work, check out Understanding NSAIDs: Mechanisms, Types, and Effects. If you need to differentiate seizure types by EEG, the Electrolyte Abnormalities and Their Impact on ECG Changes Explained resource can help rule out metabolic causes. For the neuroscience behind synaptic transmission and how drugs like benzodiazepines modulate it, refer to Drogues et Transmission Synaptique : Ecstasy, Cannabis et Neurotransmetteurs. Finally, for a review of learning and memory systems (relevant to understanding epilepsy's impact on cognition), see Module 12 : Plasticité Synaptique, Apprentissage et Mémoire - Cours Keane 17-20.
Use these mnemonics, they are free points on every pharmacology exam.
So when we go through this, we're going to cover three main things. Now, some drugs are not going to have an
indication. Some drugs are not going to have a high yield adverse drug reaction. And if that's the case, I'll point it
out. But when we go through these drugs, we want to think about the mechanism, the indication, and the main side
effects or adverse drug reaction. So the main ADRs. Um, don't worry guys. I want you to sit back, take a deep breath, and
just follow my lead. We're going to simplify all of this in a really high yield fashion. So let's start with
valproate, also known as valproic acid. So the mechanism of valproate is that we're going to inhibit or decrease the
activity at voltage gated sodium channels. In addition to that, we're going to increase the activity of GABA.
So think of sodium in this lecture as like sort of excitatory. So when you decrease voltage gated sodium channels,
we decrease the excitation that causes seizures. Likewise, GABA is an inhibitory neuron. So if we increase
activity of GABA, we're increasing inhibitory activity, which means we're getting inhibited, which tones down the
excitation in the brain that causes seizures. So valproate decreases or inhibits the voltage gated sodium
channels and increases GABA. Valproate is really a firstline medication here. And if you're taking your exam and they
want you to pick what uh anti-epileptic drug you're going to give to somebody who has a you know like a just a general
seizure um a partial or a toniconic seizure and they don't um specify a specific subtype of seizure and you'll
understand what I mean as we go through this lecture but generically speaking if you have to pick a first-line medication
valate is usually your go-to. Adverse drug reactions. Let's talk about a few. The ones you should know are
anemia, hpatotoxicity, pancreatitis, and spinobipida. Right? So, how do you remember this? Well, when
you think of valproate, I want you to think of all pro. So, you take the alpro out of valrate. So, all pro. That
reminds us of two things. The if we drop one of the L's, all pro stands for anemia, liver, pancreatitis. And then
the little R big O reminds me of the hole that you get in the neural tube defect of spinobipida. So the O is
literally just the hole or the pouch through which you have the spinobipida occurring. So all pro from volate all
pro anemia liver which is hpatto toxicity pancreatitis and then our big O is the little spinobipida. The other
reason that I think all pro is because we need to have a way to memorize the mechanism of valproate. And if you're
not a sports fan, I apologize, but an allp pro athlete who is a very salty person is Dez Bryant, the wide receiver
for the Dallas Cowboys. So that's Val Pro8. All pro from Valproate. Now let's talk about fenito. Phenito's
mechanism is that you have uh an inhibition or decrease activity at voltage gated sodium channels. So same
exact mechanism minus the GABA part. Um there's really no main indication for fenytoin. So the adverse drug reactions
that you should know about are gingivvil hyperplasia and fetal hyantoin syndrome. In addition to that I want you to know
that this drug underos zeroorder kinetics which means just to refresh your memory that the drug is eliminated
at a constant rate that does not change based on the amount of the drug. It's the same amount um per hour shall we say
that gets eliminated and it's a P450 inducer that's also really high yield. So how do we remember fanny towin? Well,
to remember fenny towin, we're going to think about a tow truck because fenny towin, you're going to need towin by a
tow truck. So, if they don't salt the roads, your car will need a towin, right? Your car will need to be towed.
The towin from fenny towin and if they don't salt the roads, salt reminding us that this inhibits voltage gated salt
channels. So, voltage gated salt channels. If they don't salt the roads, your car will need a towin. And this
pneumonic goes beyond just the mechanism because let's think about these things. Gingal hyperplasia. Well, I think about
snow hyperplasia, right? Snow everywhere. Just like the there's gingerville hyperplasia where the cells
are growing out of control. I think of salt or excuse me, snow hyperplasia. Fetal hide and towin syndrome is an easy
one to remember because the word ends in towen and fenitoin also ends in towin. So you don't even really need a
pneumonic to remember that. But fetal hide and towin syndrome just so you know and I and I do suggest that you Google
it is cranioacial abnormalities and limb problems in addition in addition to mental retardation. So that if you take
feny towin when you're pregnant your baby could have fetal hide and towin syndrome towin um and fenytowin but
again the way that I remember the this by if they don't salt the roads your car will need a towin salt for the voltage
gated salt channels um if if there's a lot of snow out there's going to be zero order right there's going to be
absolutely no order on the roads um it's a P450 inducer so if they don't salt the roads you're going to be inducing tow
trucks to come rescue the cars Gingerville hyperplasia. I think about snow hyperplasia. Just snow everywhere,
which is why you're going to need a towin when they don't salt the roads. And then fetal height and towin
syndrome. Again, easy to remember just because it ends in towin. So that's everything you should know about fenny
towin. So close your eyes, think about fenny towin. And when you can't remember anything about this drug, just remember
towin like the tow truck. Why are you being towed? Well, they didn't insult the roads, which means there's snow
everywhere. There's snow hyperplasia, zero order kinetics because there's zero order on the roads. And it's a P450
inducer because we're going to have to induce the tow trucks to come dig our cars out of the snow. So that is fenny
towin. Now we're going to talk about ethosuxomide. The mechanism of ethosomide is that it inhibits the
T-type calcium channels. So just remember the word calcium. If you see calcium, that's the answer. They're not
going to make you pick Type from any other type. You're going to see calcium and that's going to be the answer. The
indication here, and this is a really high yield one, is absance seizures. So absant seizures are always treated by
ethosomide. The main adverse drug reaction to know is Stevens Johnson syndrome. So the pneumonic here is
really really easy. Absance seizures suck or sucks. Um absance for absance seizures and sucks for suomide. So
absance seizures suck or absance seizures sucks. The other thing that I really want you guys to to memorize is I
have this clever pneumonic to remember all of the antiepileptics that cause Stephven Johnson syndrome. So Stevens
Johnson syndrome is a really really nasty rash that you can get. And if you get it, it can develop into something
which is worse called toxic epidermal necro necrolyis. And Google what that looks like. It's hideous. But what you
need to know is the drugs that cause the rash. Because if you put a patient on a drug and all of a sudden they get some
nasty looking rash, then you need to stop the drug. So Stevens Johnson syndrome, one of the drugs that causes
it is ethosomide. So the pneumonic that I have to remember the different drugs that cause it are I think about five
male friends and their names are Ethan, Carl, Larry, Steven, and Johnson. This is actually a picture of the band in
sync, but that's the picture I always I've always used in my own notes. So Ethan, Carl, Larry, Steven, and Johnson.
And each of these names signifies a drug. So ethosuxomide is Ethan. So if you give ethosomide you can call Stevens
Johnson syndrome and ethosomide is represented in the group of friends by Ethan. Of course Steven and Johnson are
not drugs but they just tell you that Ethan, Carl and Larry can cause Steven and Johnson syndrome. So Ethan is
ethosomide and as we go through this lecture you'll you'll meet Carl and you'll meet Larry. These are all drugs
that cause Stevens Johnson syndrome. So now we're going to talk about carbomazipene. So carbomazipene's
mechanism is that it increases the refractory period of voltage gated sodium channels and when you increase
the refractory period of anything it means you're increasing the time that that receptor is not working and by
doing that you're still blocking excitation and when you block excitation you treat seizures. High yield
indication here guys is trigemina nur trigeminal neuralgia. Really really high yield. The for some reason they the
boards love to go after trigeminal neuralgia. They're going to describe a patient to you who has trigeminal
neuralgia and they will ask you what drug do you give or what's the mechanism of that drug or what's the side effect
of that drug. All of this is tied together. So so pay close attention here. Carbomasopene causes Stevens
Johnson syndrome. And if you remember our boy band, our friends Ethan, Carl, Larry, Steven, and Johnson,
carbomaszipene is represented by Carl. So Carl for carbomaszipene. Let's talk about trigeminal neuralgia
really quickly. So trigeminal neuralgia is a problem in the distribution of the trigeminal nerve which supplies sensory
intervation to various muscles of the face in the V1, V2, and V3 distribution. You can see a picture of it right there.
But basically someone has sharp shooting lancinating pain over their cheek up back to just over the top of the ear.
That is trigeminal neuralgia. And the pain is debilitating. You will not miss this on an exam. If they give this to
you on USML or COMLX, it's going to be sharp shooting stabbing lancinating pain in the distribution of the muscles that
you see here. And again, they're they're innervated by the trigeminal nerve, which is why this is called trigeminal
neuralgia. So when this happens, you treat with carbomazipene. And I told you that that's super high yield. So how do
we remember this? My pneumonic is that you chew carbs with your cheek. So the the carbs for carbomazipene and you eat
or chew carbs with your cheek. So imagine literally eating a sandwich. You're going to be using the facial
muscles that are innervated from in the sensory distribution by the trigeminal nerve. So you eat carbs or you chew
carbs with your cheek. That reminds me that trigeminal neuralgia uh is treated with carbomazipene. So you chew carbs
with your cheek. And then don't forget Carl is carbomazipene in our group of friends Ethan, Carl, Larry, Steven and
Johnson. So Carl or carbomazipene will cause Stevens Johnson syndrome. Now let's talk about lamotrogene. So
lamotraine's mechanism is that it inhibits voltage gated sodium channels and it also has activity at glutamate
receptors. Now uh lamotine also is one of the drugs that causes Stevens Johnson syndrome. So Larry is lamotine. So we're
done with our group of friends now. We talked about Ethan which is ethosomide. We talked about Carl who's carbomazipene
and now we're finishing with Larry who's lamotrogene. So those three friends or those three drugs will cause Stevens
Johnson syndrome. So that's really really high yield. How do we remember that this has activity not only at
voltage gated sodium channels but also at glutamate receptors. This is really high yield um as far as mechanisms go
because it's the only drug that has activity at both voltage gated sodium and glutamate receptors. So from the
perspective of the seizure and this is our cartoon seizure. From the perspective of the seizure, if you give
somebody lamotine, it has two mechanisms at two different receptors. So the seizure who really wants you to keep
seizing, the seizure looks at this double mechanism going on and says, "Wow, you're attacking me at two
receptors." That's lameo. Layo for lamotraine. So from the perspective of the seizure, the seizure is like, "Oh,
it's so lame. You're turning me off at voltage gated sodium and glutamate receptors. Layo for lamotraine." Um, and
then don't forget Lamotroine is Larry Stevens Johnson syndrome. So, we're flying guys. I hope you're able to keep
up here, but it's not that bad if you get these pneumonics down. Let's quickly talk about some of the easier ones to
remember. Now, so these are uh bzzoazipines and barbbiterates. And really, the only thing that you need to
know about these guys is their mechanism. So, they increase the activity at the GABA A receptor. And the
way that they do this is that benzo increase the frequency of chloride channel opening and barbituates increase
the duration of chloride channel opening. And this I want to pause for a second because this is really really
high yield. It's not difficult to remember but it's high yield because exams love to go after the differences
in these mechanisms because the only difference is the word frequency or the word duration. And you will see a
question on this in some question bank maybe even on your USML or complex. So let's talk about this. How do you
remember which one's frequency and which one's duration? Well, instead of saying barbbiterate, I want you to say
barbidurate. Barberate. So, dur for duration. So, barbbiterates increase the duration of chloride channel opening and
benzo increase the frequency of chloride channel opening. So, if you remember the barberate just by process of
elimination, you'll know that benzo have to be frequency. So, that's barbbiterate for dur for duration. Um, the only other
thing is that you should know that benzo are used as abortive means of stopping a seizure. So, if someone's seizing on the
table and you need to stop the seizure, you you give them a benzo. Um, that's really all you need to know about benzos
and barbiterates as far as uh seizures are concerned. We're going to talk now about levitam.
So, the mechanism is unknown and you may think that that's something that you won't be asked, but I have seen the
question come up and the answer is unknown mechanism. Or maybe in the clinical vignette they'll say a drug
with an unknown mechanism blahy blahy blah what's the drug? So you got to know that levitator acetam is an unknown
mechanism. I know that sounds funny sounds stupid but just know it. So how do we remember this? I want you to think
when you think of leviter acetam I want you to think of a magician making somebody levitate. How does he do the
levitate trick? I don't know. That's I don't know. Reminds me that the mechanism is unknown. So how do you
levitate? I don't know. Unknown mechanism. I just don't know. Levitate for levator acetam. I mean, how simple
can we get, guys? I'm really boiling this down. Let's talk about two of the lower yield drugs that I've included for
completeness sake. Tiagabine and vagabitan. And I'm probably butchering the pronunciation here, but who cares?
Mechanism GABA. It has activity at GABA. Um, the way that you remember this is you look at the name T gabin and vaba.
So, GABA or GABA is in the name. It's got activity at GABA. That's literally all you need to know. So, if you see
this drug and they ask you the mechanism, look at the name. take the gas and take the easy point. We're going
to finish up um with topyramate. So topyramate mechanism is that it it inhibits voltage gated sodium channels
just like a lot of the other drugs we've talked about today. Um how do we remember this? Well in with topyramate I
want you to think of a top pirate mate or a pirate ship. Here's our pirate ship. And just so you know a pirate ship
sails on saltwater salt for voltage gated salt channels. So that's it guys. That is all the anti-epileptic drugs.
That is all of their mechanisms all with pneumonics. All of the high yield indications and adverse drug reactions.
Some things in closing and in summary that I would like you to remember is uh Carl, Larry, Ethan, Steven, and Johnson.
The five friends who cause Stevens Johnson syndrome. You can remember Ethan, Larry, and Carl as ethosomide,
lamotrogene, and carbomasene. Remember that carbomasopene treats trigeminal neuralgia. Remember that ethosomide
treats absance seizures and remember some of the other stuff as far as mechanisms are concerned. And when
you're learning the mechanisms, it's something that you just unfortunately have to memorize. So go back and use
these pneumonics because they're free points. Good luck.
Valproate (valproic acid) is the first-line treatment for generalized seizures, including tonic-clonic and partial seizures, and is considered the default option when no specific seizure type is mentioned. Its main adverse effects are anemia, hepatotoxicity, pancreatitis, and spina bifida (neural tube defect), which can be remembered with the mnemonic "All-Pro" (A=Anemia, L=Liver, P=Pancreatitis, O=Spina bifida).
Phenytoin is characterized by zero-order kinetics, meaning it is eliminated at a constant rate regardless of dose, and it causes gingival hyperplasia (gum overgrowth). Use the mnemonic "Towin"—think of needing a tow truck on an icy road: zero-order kinetics (no order), voltage-gated sodium channels (salt channels), gingival hyperplasia (snow, or gum overgrowth), and it is a P450 inducer (inducing tow trucks), with fetal hydantoin syndrome (name ends in "-to win").
Ethosuximide works by inhibiting T-type calcium channels, making it the go-to treatment for absence seizures. Its key adverse effect is Stevens-Johnson syndrome, a severe rash, which can be remembered with the mnemonic that "absence seizures suck" (Suc-cinimide), and it is part of the *NSYNC band mnemonic: Ethan (ethosuximide), Carl (carbamazepine), and Larry (lamotrigine) can all cause Stevens-Johnson syndrome.
Carbamazepine is highly specific for trigeminal neuralgia, which causes sharp, shooting pain along the trigeminal nerve (V1/V2/V3 distribution); a mnemonic is "you chew carbs with your cheek." It shares the side effect of Stevens-Johnson syndrome with ethosuximide and lamotrigine, as all three are part of the *NSYNC mnemonic (Carl for carbamazepine).
Lamotrigine has a unique dual mechanism: it inhibits voltage-gated sodium channels and also has activity at glutamate receptors, making it the only anti-epileptic drug with this combination. A mnemonic is to imagine the seizure saying, "Wow, you're attacking me at two receptors, that's lame-o" (la-mo-trigine).
Benzodiazepines increase the frequency of chloride channel opening at GABA-A receptors, while barbiturates increase the duration of opening. Use the mnemonic "Bar-bi-dur-ate" for barbiturates (duration), and by elimination, benzodiazepines affect frequency. Benzodiazepines are used as abortive therapy for active seizures.
Levetiracetam's mechanism is unknown, which is frequently tested on exams. Remember it with the mnemonic: imagine a magician making someone levitate, and when asked how, you respond, "I don't know."
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