Speaker 1: All right, so we're going to be doing a farm
review for our antipsychotic medications. Thank you so much for
the support of the channel. Let's go ahead and get
started with the basics. So we're going to be going
over our first gens aka are typical antipsychotics, and our
second gens known as atypicals. If you ever forget which
generation is typical and which is atypical, you hold two
fingers up for your second generation meds. Turn those two
fingers upside down and it turns into an A four atypicals. Now,
when we're talking about our antipsychotics and the conditions they treat,
most notably schizophrenia, the leading theory, although still an active
area of research, is that dopamine plays a central role.
This regulation of dopamine signaling is thought to contribute to disease,
and many antipsychotics exert their therapeutic effects by altering dopamine
signaling in the brain. So to understand these mets, we've
got to learn a little bit more about our friend
dopamine and four specific dopamine pathways in the brain. Let's
first talk about what they're supposed to do, which will
help us understand what happens when things go wrong, as
well as where our meds exert their therapeutic effect. So
for dopamine pathways, you need to know mesolimbic, mesocritical, nigrostria,
and tubero infintit. Let's first start with the mesolymbic pathway.
So the mesolimbic dopamine pathway is a little pathway between
the ventral tegmenttal area and the nucleus eccumbents of the brain.
This is our reward center, so things like motivation, desire, pleasure.
It's actually the primary area cocaine targets. So something feels good,
this area of your brain motivates you to do it again.
For example, purposes, I like to remember one word to
associate which each of these, which helps remember key components.
For mesolimbic, it's going to be motivation, and it's also
important to know that excess dopamine here is thought to
contribute to the positive symptoms we see in schizophrenium, like
hallucinations and delusions. The next area we're going to be
talking about is our mesocortical pathway. This connects the VTA
to the pre frontal cortex. Dopamine here regulates emotions, cognition,
executive function, et cetera. The one word association here is
mood and schizophrenia. Dopamine here is thought to be low
or hypo functioning, contributing to our negative symptoms flat affect,
emotional withdrawal, and edonia aka inability to feel pleasure. The
next two pathways, understanding their normal function is key because
it's going to help us understand many of the adverse
effects associated with the medications that will discuss shortly. So first,
starting with the nigrostriadl which originates in the substantia niagra.
Dopamine in this pathway plays an important role in movement
and coordination. You can probably see where this is going.
If dopamine promotes movement in this pathway, what might happen
when an antipsychotic blocks too much dopamine here we'll talk
more about that in just a moment. The one key
to remember for the negrostrital pathway is going to be movement.
And then finally, we have the tubero infandibular pathways, which
connects the hypothalamus to the pituitary gland. Dopamine in this
pathway inhibits the release of prolactin, and prolactin, as we know,
promotes lactation among other things. Again, think about what might
happen here if we block dopamine with our antipsychotics, and
more about that soon. So your one word association for
tubero infindibular is going to be milk, and that's your
dopamine pathways mesolympic equals motivation, mesocortical mood, negrostrital movement, and
tubero infandibular milk. Now that we have our framework, let's
talk about our meds. Starting with are typical or first
generation antipsychotics. So these are the ogs first developed in
the nineteen fifties, with the first antipsychotic drug being chloropromazine.
Interestingly enough, we still use chloropomazine today, but not so
much for its antipsychotic properties, but actually for severe hiccups.
It's true, so the use the first gens has declined
over the years, not due to lack of efficacy, but
due to their poor side effect profile compared to the
newer second generation antipsychotics. Still got to know them, though,
So this class includes a number of different medications which
are classified by how potently they block D two receptors.
Our high potency meds being halo paradol, flu fhenazine, loxipine,
pure fenazine, pimozide, thiothyxine, and triflu parizine. And then we
have our low potency meds, which are going to be
thioritizine and chlorpromazine. There's a whole lot of meds here,
and if you just want to remember one by all means,
let it be haliparadol. This is what will likely be
tested on as it's one of the most commonly used
first gens. If you want to remember most of them,
remember Halo paradal and your azines. The azenes suffix is
seen in a majority of the first gen antipsychotics chloroprome, azine,
flu fen azene, etc. I used to have this visual
of the first edition of Halo magazine like Halo the
video game, because I'm a nerd and I used to
play a lot Halo when I was younger. So Halo
help helps you remember, Halo Paradol magazine helps you remember
your azine meds, and first edition helps you remember that
these are your first gen antipsychotics. So those are your meds.
Let's talk about the mechanism of action next. Now, all antipsychotics,
whether it's first or second gen, are going to mess
with dopamine in one way or another, depending on the
med different strength of dopamine manipulation, and varying methods. But
in the case of first gen, the primary mechanism is
through inhibition of D two dopamine receptors in the brain.
The therapeutic effect of these drugs is by post synaptic
blockade of dopamine D two receptors in the brain. So
blocking dopamine receptors, how does that help a patient with schizophrenia,
for instance? And to answer that, we need to revisit
the dopamine pathways we discussed earlier, specifically the mesolimbic pathway
our motivation center, where excess dopamine here is thought to
contribute to the positive symptoms of schizophrenia, as we went
over hallucinations and delusions, et cetera. So if we block
dopamine receptors in this pathway with a first gen theoretically
we can reduce the symptoms. And there is a therapeutic
window for the number of D two receptors blocked, typically
around sixty five to seventy percent. D two blockade is
the sweet spot. You block less, decrease efficacy. You block more,
you have more adverse effects. Now, what about the mesocortical pathway.
Remember mesocortical equals mood, where dopamine is already thought to
be low in schizophrenia, causing our negative symptoms. And since
first gens further block dopamine in this pathway, it's thought
that they have little effect on negative symptoms and potentially
potentially may worsen them in some patients, although evidence for
this remains limited and a lot of this is still
being researched. So for the exam, focus on first generation
antipsychotics blocking D two receptors in the brain, reducing positive
symptoms for your mechanism of action, let's move on to
indications for these meds. Of course, schizophrenia and schizoeffective disorders,
acute mania a severe episodes of bipolar mania that is
usually combined with lithium, major depressive disorder with psychotic features
and severe agitation, plus a number of other conditions, and
like we discussed before, first generation antipsychotics can treat these conditions,
but they have largely been replaced by second generation or
atypical antipsychotics, particularly in the treatment of schizophrenia due to
their higher risk of movement or extra perimidal side effects,
So I wouldn't focus too much on the indications as
you won't use these that often, except in the case
of severe agitation and the impatient or emergency setting where
they're still pretty commonly used. This will usually be with
a rapid acting first gen like helo paradol combined with
the benzo. All Right, the next part is the most important,
and that's the adverse effects. There are many adverse effects
associated with antipsychotics, and I could easily spend an entire
lesson covering all of them, but for this review, we're
going to focus on the high fieled effects for your exams,
especially those that are more commonly associated with your first
gen antipsychotics. So for adverse effects, I want you to
remember to dread neuroliptic malignant syndrome ED neualiptic malignant syndrome.
You'll know the highest yield adverse effects for your first
gens and also know to dread and or elliptic malignant syndrome,
which is the most feared adverse effect of this class,
as it can be fatal. So let's start with the
dread portion of the mnemonic, which helps us remember our
extra perameteral side effects. These are our movement disorders, which
are more common in first gens. Let's first start with
why this happens. Then we'll talk about which specific movement
disorders to know for the exam. So let's go back
again to the dopamine pathways. Which pathway do you think
contributes to our movement disorders with these mets. That's right,
the negrostrital pathway, the dopamine highway that control movement and coordination.
So if this movement pathway is fueled by dopamine, what
do you think will happen when we throw a first
gen in there, which we know blocks dopamine. Not surprisingly,
movement disorders develop. In fact, blocking dopamine in the negrostrital
pathway creates a situation similar to Parkinson's disease, which is
why antipsychotic induced movement disorders closely resemble Parkinsonian symptoms. So
now let's talk about these specific extra perametal symptoms you
need to know ZH using the dreadnomonic dr EA D
starting with D which stands for dystonia, Acute dystonia is
one of the earliest adverse effects, peaking at around twenty
four to forty eight hours from the initiation of therapy,
and it involves involuntary muscle contractions or spasms of the face, neck, eyes, back,
and muscle stiffness and contractions, which can actually be quite painful. Next,
the R is going to stand for rigidity, so rigidity
of the limbs resistant to passive movement, which is one
of the most obvious features of drug induced parkinsonism we
can see in these patients. It may present as lead
pipe or codwheal rigidity. Next, the E stands for I deviation. Now,
this is related to the acute dystonia and is formally
called oculogyric crisis where there is this spasmodic deviation of
the extra ocular muscles causing the eyes to look upward.
Not super high yield, but just be aware of it.
Next to the A stands for Acathesia is uncontrollable inner
restlessness and compelling urge to move the body tapping, rocking
back and forth, and it can be one of the
most distressing side effects of these drugs. So I do
not intend to make light of this with my sillynomodic.
This is just how I remembered it. Acathesia. I used
to think of a cat in acathesia, a restless cat
that can't sit still, constantly pacing, scratching, and tapping its
paws like most cats do to help remember the compelling
urge to move the body, tapping, etc. Seen in acat theesia.
And finally, the D stands for dyskinesia, as in tardive diskanesia.
Tardiv diskanesia is a late manifestation, usually occurring after months
of being on the medication. The word tardive actually is
derived from the Latin term tartis, meaning late or tardi,
which makes sense as this is a late manifestation occurring
after many months. So while the arms, legs, and trunk
can be affected with this condition, tardev diskeanesia mainly targets
the tongue and mouth, leading to these unique manifestations with
twisting of the tongue, chewing, grimacing movements of the face.
The word tar and tardive diskeanesia would always make me
think of what your face would look like if you
were chewing a piece of sticky, chewy tar all right,
So those are your extra pyramidal symptoms, very high yield
for our again, remember dread dystonia, rigidity, I deviation, acathesia, dyskinesia. Next,
let's talk about neualeptic malignant syndrome or NMS. Why do
we dread NMS with our first gens. Well, that's because
this complication well rare can be fatal. NMS is a
neurologic emergency associated most commonly with the use of first
generation antipsychotics, and that's why you dread NMS with the
first gens. Manifestations of NMS are fever, muscle rigidity, autonomic
instability usually accompanied by rabdough and creating kinase elevation. Treatment
is fairly high yield and easy to remember as you
treat with the four DS. The four DS are discontinuation
of the offending agent. In this case, we would be antipsychotics.
XD is for dantriline, a muscle relaxant. Next is your
D two agonist like bromocryptine, and finally diazepam or other
benzos to mitigate agitation. Now, there are of course a
number of other adverse effects QT prolongation, prolactant elevation. Since
they're non selective, they also may block histamine alpha one
and muscarinic receptors, so there can be sedation, hypo tension,
urinary retention. But for the exam, I'd stick to dread
nms as that's the highest yield ADRs for this class.
And that brings us to our second generation or our
atypical antipsychotics. So first, why are they called atypical? What
makes them atypical? Well, primarily because of the lower propensity
to induce EPs or movement disorders like we just talked
about with our first gens, and it also originally implied
that these newer drugs were fundamentally different than first gens.
But not all second generation antipsychotics behave the same way,
so the naming system it's not perfect. But with that
being said, let's first talk about what medications are included
in this class. So the men's included in this class
include erapiprasol a, centipine, brex pipersol, cariprazine, closetpine, eloparodone, lumteperone, luracidone, olanzipine, paloparidone, quetiapine, resparodone,
and zeprasidone, Like, seriously, arery, Katie mee? Who's gonna remember
all of that? So here's the good news. From exam standpoint,
there's really only four to focus on. The four that
are always test it on due to their adverse effects
are closipine, resparidone, lanzipene, and quotipine, So you need to
know those closipine, resparadone, lanzipene, quotipine. I just remember the
sentence crocs are atypical shoes. Crocs are atypical shoes. Crocs
are spelled cr Q. The first letters of closipine, resparodone, lanzipine,
and quotiapine are atypical shoes. Atypical helps you remember that
these are atypical antipsychotics and no offense to anyone wearing crocs,
but they kind of are atypical shoes. So again, closeipine, resparodone, olanzipene,
quotiapine aka crocs are atypical shoes. Next, let's talk about
how these meds work, which is by inhibiting D two
dopamine receptors plus serotonin five HT two A receptors. Now,
before we dive deeper, I want to point out that
second generation antipsychotics are a diverse group of meds, and
not all of them follow this exact mechanism. For example,
era pippersol, brex pippersol, and cariprazine are sometimes referred to
as third gen antipsychotics by some sources because they act
as partial dopamine agonists rather than pure dopamine blockers. But
with that being said, the general mechanism you should focus
on for your exam for most of these meds is
that second generation antipsychotics affect both dopamine and serotonin signaling. So,
like first gen antipsychotics, they block post synaptic dopamine D
two receptors. But what really sets them apart as their
additional blockade of serotonin receptors, particularly the five HT two
A receptor. In many of these meds, the serotonin blocking
effects are relatively greater than their dopamine blocking effects. Additionally,
some second gen agents will exhibit lower D two receptor
occupancy or more transient binding to these dopamine receptors, a
distinction that will become important when we discuss adverse effects later. Now. Initially,
it was thought that this additional serotonin blockade made them
more effective for treating negative symptoms of schizophrenia, but the
evidence really has been mixed and many studies have found
similar efficacy between first and second generation antipsychotics. So the
key distinction to remember for the exam first gens primarily
block dopamine. Second gens generally effect both dopamine and serotonin.
All right, indications, of course, we are going to have
schizophrenia with our second gens, which are going to be
preferred over the first gens for this condition due to
the lower incidents of extra parameiteral symptoms ecthesia, dystonia, et cetera.
Bipolar disorder is another one, and major depressive disorder as
an adjunctive therapy. There are others korea and Huntington disease,
postpartum psychosis, but focus on those three, with schizophrenia being
at the top of that list. Next, let's talk about
the adverse effects, which is probably the most commonly tested
on component. So let's start with what we've already touched
on previously. Second genss can cause extra parameteral symptoms, but
less often compared to our first gens. So why do
these movement disorders occur less often with second gens? Well
back to the MOA. These drugs are still dopamine blockers,
but they're also serotonin blockers, and comparatively, their serotonin receptor
binding exceeds their dopamine receptor binding, which varies by the
specific drug, but as a general principle, second generation antipsychotics
bind more loosely to D two receptors compared to first
generation agents. The theory is weaker D two binding allows
more dopamine activity to be preserved in pathways like the
nigrostriatal tract, which translates to a lower risk of movement disorders.
So no that they still can cause them, but less often.
Most importantly, next, let's talk about the other adverse effects,
starting with the most important and prominent for your second GENS,
which is going to be metabolic syndrome. You'll think weight gain, diabetes,
dyslibidemia as a class. This is the most important adverse
effect for you to know. For first gens, it was
your extra paramidal. For second gens, it is metabolic syndrome.
It's so prevalent with this class it's recommended to actually
monitor weight, BP, fasting, glucose, and lipids when patients are
started on these meds. Now, when we're talking about weight gain,
even though all of the second gens can cause weight gain,
there's one that you need to know that causes it
the most, and that's going to be olanzipine. A Lenzopene
is the second generation antipsychotic most commonly associated with significant
weight gain and other metabolic complications. Clauspine causes a similar
degree of weight gain, but it's got way other high
yield associations will go for shortly, so for exams, think
olanzapine equals obesity. Luckily, it's the only antipsychotic that starts
with an O. The O in your mind should stand
for obesity when you see this on your exam. Next
is going to be hyper prolactinemia, oh, elevated prolactin levels. Now,
this can of course happen with our first gens, like haloparadol,
but I wanted a wait to speak about this until
we got to our second gens because there's a second
gen med notorious for this and therefore the one you
need to know for your exam before we get to that.
Why do we have prolactin elevation and development of things
like lactaria in the first place. Back to the dopamine
highway again, remember the tubera in finndibular track or dopamine
travel to the pituitary to inhibit the secretion of prolactin. Well,
when we blocked dopamine here with our antipsychotics, we remove
prolactin inhibition and prolactin levels where therefore rise and patients
can develop hyper prolactinemia with adverse effects like glactariea among
other things as well. So the one drug you have
to know that is notorious for this is resperidone. Now,
we just went over the moa of second gens and
I made a point to mention that second gens are
generally weaker D two lockers. So why does resperidone, a
second generation drug, cause hyperprolectinemia so frequently, which is a
side effect driven by dopemine blockade. And the answer to
that is Resparadone is somewhat of an outlier among the atypicals.
Unlike many other drugs in this class, it functions more
like a first gen in that it's a more potent
D two blocker, and that's why we see dopemine block
mediated adverse effects like hyperprolactinemia as well as more extra
paramidal symptoms. So while there are other drugs that can
cause hyperprolactinemia, do not forget resparadone as it's one of
the most common to cause this and it's always tested
on the way that you can remember resparadone is linked
to hyperprolactinemia and galactorea is by instead of remembering resperidone,
remember it as respey dairy. Not a very appropriatemnomonic and
I apologize, but respeery dairy dairy dai r y instead
of resperidone helps remember the galactorea aka milk discharge from
the breast associated with this medication secondary to hyper prolectinemia.
So again remember instead of resperidone, remember it as respery dairy.
Next going to be QT prolongation. So your antipsychotics can
cause QT prolongation, but there's two second gens that cause
it the most, and these are going to be quotiopine
and zeprasidone. And it's easy to remember that quotiapine causes
QT prolongation because the Q is far from the T
and quotiapine the Q is far from the t and
the spelling of quotiopine q u E t ia pi
n E, which helps remember. This medication, along with zeprasidone,
have the highest risk of QT prolongation compared to the
other meds in this class. Next, we have undone. A granulocytosis.
This is a dangerous and potentially deadly drop in white
blood cells, more specifically neutrophils. And when you hear a
granulo psytosis on a psychic exam, closipine is the answer
that you are looking for. Closipine is a second generation antipsychotic,
but it's quite different than all of the other drugs
in this class. It's actually way way more effective, arguably
the most effective antipsychotic we have, especially in the treatment
of resistant schizophreniam. So if it's so damn effective why
isn't closipene first line for everybody with schizophrenia well a granulocytosis.
This medication was initially tested in patients in Finland in
the nineteen seventies. They found great efficacy, but people started
dying secondary to a granulocytosis. So cloudspin is still used
in treatment resistant schizophrenia, and it's actually first line for
the specific indication, of course, after patients have tried many
other meds in the class, but it requires frequent labs
to assess the absolute neutrophil count as frequent as every
week during the first six months and then less so thereafter,
so you have to know this association with this medication.
It is super high yield. So remember Closipine is a
white cell fiend. Closepine is a white cell fiend. Claspine
is I don't know, snatching up all of those white cells,
all those neutrophils and maybe like eating them or something
in the visual in your head. But closibine is a
white cell fiend, which helps you remember these super high
yield adverse effects of a granulocytosis associated with this medication.
You cannot forget that, So those are your adverse effect
for your second gens. There are, of course plenty of
others neueleiptic malignant syndrome, although this is more common in
first gen on it for that class, sedation, hypotension, urinary retention,
thyroid abnormalities, among others. But the focus should be first
and foremost on metabolic syndrome with weight gain, diabetes, et cetera.
Remember the OH and Olanzipine stands for obesity, Rosperidone associated
with hyperprolactinemia in galactoia aka risperidairy QT prolongation with zeprasidone
in quotypine. Remember the key was far from the T
in quotypine. A granliocytosis with closipine because closipine is a
white cell fiene. And of course remember your extra perramidal
symptoms happen but less frequent compared to first gens, and
that is your antipsychotics. I hope that was helpful. Thank
you so much for listening, and as always, best of
luck in school