Antipsychotics Mnemonics (Memorable Psychopharmacology Lecture 4)

Summary

This script delves into antipsychotic medications, crucial for treating schizophrenia and other psychotic disorders. It distinguishes between first-generation 'typical' and second-generation 'atypical' antipsychotics, highlighting the former's higher risk of motor side effects due to dopamine receptor blockage, and the latter's metabolic issues like obesity and diabetes. The summary also touches on the importance of dopamine receptor subtype D2 in their mechanism, the wide range of side effects, and the significance of patient compliance in treatment efficacy.

Takeaways

• 💊 Antipsychotics are medications primarily used for treating schizophrenia and other psychotic disorders, divided into first-generation (typical) and second-generation (atypical) categories.
• 🧠 First-generation antipsychotics block dopamine receptors more aggressively, leading to motor and neurologic side effects, while atypicals have less affinity for the dopamine receptor but can cause metabolic issues like obesity and diabetes.
• 📉 Antipsychotics' efficacy and side effects are largely due to their modulation of dopamine, highlighting the neurotransmitter's role in various cognitive and motor functions.
• 🔑 A high-yield tip for remembering antipsychotics' mechanism is that they work on the dopamine receptor subtype D2, with 'D2R' sounding like 'dour', relating to taking a 'dour' from reality.
• 🚫 Despite their effectiveness, antipsychotics come with a wide array of side effects, emphasizing the importance of considering the third rule of neurotransmission: with great power comes great responsibility.
• 🚶‍♂️ Antipsychotics can induce Parkinson's disease-like symptoms, as they effectively create a form of medically induced Parkinson's with motor and cognitive effects.
• 🤐 Extrapyramidal side effects (EPS) are motor effects outside the medullary pyramids and include acute dystonia, akathisia, and akinesia, which can be remembered as 'muscle rustle and hustle'.
• 👄 Tardive dyskinesia is a serious, potentially irreversible side effect of long-term use of first-generation antipsychotics, characterized by involuntary rhythmic movements of the perioral muscles.
• 🌡 Neuroleptic malignant syndrome (NMS) is a life-threatening outcome of antipsychotic use, presenting with symptoms like severe confusion, agitation, and high fever, with a significant mortality rate.
• 🍼 Hyperprolactinemia is another side effect of antipsychotics, particularly risperidone, causing hormonal imbalances like breast enlargement in males due to dopamine's role in inhibiting prolactin.
• 📦 Antipsychotics are available in various dosage forms, including oral, dissolvable, intravenous, and intramuscular, with depot forms providing long-term control but requiring caution due to their irreversible nature once administered.

Q & A

What are the two main categories of antipsychotic medications?

The two main categories of antipsychotic medications are first-generation or typical antipsychotics and second-generation or atypical antipsychotics.

What is the primary difference between typical and atypical antipsychotics?

Typical antipsychotics work primarily by blocking dopamine receptors, which can lead to more motor and neurologic side effects, while atypical antipsychotics have less affinity for the dopamine receptor and can cause serious metabolic issues such as obesity, diabetes, and hyperlipidemia.

Why are antipsychotics sometimes referred to as 'medically induced Parkinson's disease'?

Antipsychotics can induce features of Parkinson's disease because they block dopamine, leading to motor and cognitive effects similar to those seen in Parkinson's, such as the 'Thorazine shuffle'.

What is the significance of the dopamine receptor subtype D2 in the context of antipsychotics?

The D2 receptor is significant because antipsychotics work on this receptor subtype. However, it's controversial as second-generation antipsychotics have relatively little activity at the D2 receptor.

What are the three main types of extrapyramidal side effects associated with antipsychotic medications?

The three main types of extrapyramidal side effects are acute dystonia, akathisia, and akinesia.

What is tardive dyskinesia and why is it a concern with long-term antipsychotic use?

Tardive dyskinesia is a condition characterized by involuntary, repetitive movements, often involving the face and tongue. It is a concern because it can be irreversible and affect a patient's quality of life negatively.

What is neuroleptic malignant syndrome and why is it considered serious?

Neuroleptic malignant syndrome is a life-threatening condition associated with antipsychotic use, characterized by fever, muscle rigidity, altered mental status, and autonomic dysfunction. It has a high mortality rate and requires immediate treatment.

Why is clozapine considered the most effective antipsychotic but not a first-line treatment?

Clozapine is considered the most effective antipsychotic due to its high efficacy rate, but it is not a first-line treatment because of the risk of agranulocytosis, a potentially deadly side effect where white blood cells are depleted.

How do atypical antipsychotics differ from typical antipsychotics in terms of side effects?

Atypical antipsychotics have fewer neurologic side effects like extrapyramidal symptoms (EPS) compared to typical antipsychotics but have a higher risk of metabolic and endocrine side effects, such as weight gain, diabetes, and hyperlipidemia.

What is the unique mechanism of action of aripiprazole (Abilify) and how does it differ from other antipsychotics?

Aripiprazole is unique because it acts as a partial agonist for both dopamine and serotonin receptors, rather than completely blocking them. This dual mechanism can be helpful for maintenance therapy and is sometimes used to augment antidepressant treatment.

Why is patient compliance important when considering the dosage forms of antipsychotics?

Patient compliance is crucial because without it, the effectiveness of antipsychotic treatment is greatly reduced. Different dosage forms, such as dissolvable, intravenous, or depot injections, can help ensure medication adherence, especially for patients who may not take medications regularly.

Outlines

00:00

💊 Antipsychotic Medications Overview

This paragraph introduces antipsychotic medications, which are primarily used for treating schizophrenia and other psychotic disorders. It distinguishes between first-generation (typical) and second-generation (atypical) antipsychotics, noting that while typicals block dopamine receptors more strongly, leading to motor and neurologic side effects, atypicals can cause metabolic issues like obesity, diabetes, and hyperlipidemia. The paragraph also emphasizes the importance of dopamine receptor subtype D2 in antipsychotic action and the significant side effects associated with these medications, including effects on drive, attention, and motor pathways, which can mimic Parkinson's disease symptoms. Neurotransmission's third rule is highlighted, indicating that the power of antipsychotics comes with great responsibility.

05:02

🏥 Extrapyramidal Side Effects of Antipsychotics

The second paragraph delves into the extrapyramidal side effects of antipsychotics, which affect involuntary muscles outside the medullary pyramids. It outlines three main types of these side effects: acute dystonia, akathisia, and akinesia, which present at different stages after medication administration. The paragraph provides examples and management strategies for these conditions, such as using anticholinergic agents for acute dystonia. It also discusses the serious long-term effect known as tardive dyskinesia, which can be irreversible and significantly impact a patient's quality of life. The importance of patient compliance and various dosage forms of antipsychotics, including dissolvable forms and depot injections, is also highlighted.

10:02

🛑 Severe Side Effects and Dosing Forms of Antipsychotics

This paragraph discusses severe side effects associated with antipsychotic use, such as hyperprolactinemia, which can cause breast enlargement in males, and neuroleptic malignant syndrome, a life-threatening condition with a high mortality rate. It also addresses various dosing forms of antipsychotics, emphasizing the importance of patient compliance and the different administration routes, including oral, intravenous, and intramuscular injections. The paragraph provides a mnemonic to remember the relationship between dantrolene and neuroleptic malignant syndrome and stresses the need for caution when using depot forms of antipsychotics to avoid long-term allergic reactions.

15:02

💡 First-Generation Antipsychotics: Mechanism and Side Effects

The fourth paragraph focuses on first-generation or typical antipsychotics, starting with chlorpromazine, the first antipsychotic discovered. It explains the broad receptor targeting of chlorpromazine, which results in a wide range of side effects, and contrasts it with other typical antipsychotics like haloperidol, which is more selective for the D2 receptor but can still cause extrapyramidal side effects. The paragraph also mentions the importance of knowing the different forms of antipsychotics, such as the decanoate form, which provides long-lasting effects, and the need to ensure patient tolerance before administering depot injections.

20:04

🌟 Second-Generation Antipsychotics: Efficacy and Metabolic Risks

The final paragraph covers second-generation or atypical antipsychotics, highlighting their lower risk of extrapyramidal side effects but higher risk of metabolic side effects. It discusses several atypical antipsychotics, including clozapine, known for its high efficacy but also its risk of agranulocytosis; olanzapine, widely prescribed but associated with weight gain; risperidone, which can cause gynecomastia; quetiapine, known for its sedating effects; ziprasidone, noted for QT interval prolongation; and aripiprazole, which is unique for its partial agonist action on dopamine and serotonin receptors. The paragraph concludes with a reminder of the importance of physician training in mental health for treating psychosis and the need for primary care providers to be aware of common treatment strategies and side effects.

Keywords

💡Antipsychotics

Antipsychotics are a class of medications primarily used to treat schizophrenia and other psychotic disorders. They are divided into two main categories: first-generation (typical) and second-generation (atypical). The script discusses the differences in their mechanism of action, with typical antipsychotics blocking dopamine receptors more aggressively, leading to motor and neurologic side effects, while atypicals have less affinity for the dopamine receptor but can cause metabolic issues.

💡Dopamine receptor subtype D2

The dopamine receptor subtype D2 is a specific type of dopamine receptor that antipsychotics work on. The script mentions that antipsychotics, particularly first-generation ones, work on this receptor, although it also notes some controversy since second-generation antipsychotics have relatively less activity at the D2 receptor. This receptor is crucial for understanding the effects and side effects of antipsychotic medications.

💡Psychosis

Psychosis refers to a mental state characterized by a disconnection from reality, often involving hallucinations and delusions. Antipsychotics work by blocking pathways in the brain that contribute to psychotic thoughts. The script uses the term to describe the primary condition that antipsychotics aim to treat and illustrates the effects of these medications on both patients with schizophrenia and healthy individuals.

💡Extrapyramidal side effects (EPS)

Extrapyramidal side effects are motor effects that occur outside of the pyramidal motor system, often as a result of blocking dopamine receptors. The script discusses three main types of EPS: acute dystonia, akathisia, and akinesia. These side effects are associated with first-generation antipsychotics and are a significant concern due to their impact on patient movement and behavior.

💡Tardive dyskinesia

Tardive dyskinesia is a serious side effect of long-term use of first-generation antipsychotics, characterized by involuntary, repetitive movements, often of the face and tongue. The script warns of its potential irreversibility and the impact on a patient's quality of life, emphasizing the importance of careful antipsychotic use to avoid this condition.

💡Neuroleptic malignant syndrome (NMS)

Neuroleptic malignant syndrome is a rare but life-threatening side effect of antipsychotic use, characterized by fever, muscle rigidity, and altered mental status. The script describes it as a serious event with a high mortality rate and mentions the importance of recognizing the symptoms and treating it promptly with medications like dantrolene.

💡Hyperprolactinemia

Hyperprolactinemia is a condition characterized by abnormally high levels of prolactin in the blood, which can cause symptoms such as breast enlargement and lactation. The script relates this side effect to the inhibition of dopamine by antipsychotics, as dopamine normally inhibits prolactin secretion, and mentions risperidone as a medication notably associated with this side effect.

💡Clozapine

Clozapine, brand-named Clozaril, is an atypical antipsychotic that the script describes as highly effective against schizophrenia but with a significant risk of agranulocytosis, a potentially fatal side effect. It is not a first-line treatment due to this risk, but it is considered for patients who have not responded to other treatments.

💡Olanzapine

Olanzapine, brand-named Zyprexa, is another atypical antipsychotic highlighted in the script for its high efficacy and widespread prescription. It is noted for its potential to cause significant weight gain and metabolic side effects, which is a common concern with atypical antipsychotics.

💡Risperidone

Risperidone, brand-named Risperdal, is a second-generation antipsychotic that the script describes as having a lower risk of EPS but a higher risk of metabolic side effects. It is noted for being less sedating, which can be beneficial in elderly patients, but also for its potential to cause gynecomastia in males.

💡Aripiprazole

Aripiprazole, brand-named Abilify, is a newer antipsychotic with a unique mechanism of action as a partial agonist of both dopamine and serotonin receptors. The script explains that this dual action can be helpful for maintenance therapy in schizophrenia and for augmenting antidepressants in the treatment of major depression.

Highlights

Antipsychotics are divided into first-generation (typical) and second-generation (atypical) categories.

Typical antipsychotics block dopamine receptors more aggressively, leading to motor and neurologic side effects.

Atypical antipsychotics have less affinity for dopamine receptors, causing fewer motor side effects but potentially serious metabolic issues.

Metabolic issues from antipsychotics can shorten lifespan, emphasizing the importance of monitoring weight and health.

Antipsychotics work on the dopamine receptor subtype D2, with second-generation having less activity at this receptor.

Antipsychotics are effective for psychosis but also affect drive and attention, impacting all thoughts, not just psychotic ones.

Use of antipsychotics can induce Parkinson's disease-like symptoms due to their effect on dopamine levels.

Extrapyramidal side effects (EPS) are motor effects outside the medullary pyramids and include acute dystonia, akathisia, and akinesia.

Tardive dyskinesia is a serious, potentially irreversible side effect of long-term antipsychotic use.

Hyperprolactinemia is a side effect of antipsychotics, causing hormonal imbalances like breast enlargement in males.

Neuroleptic malignant syndrome is a life-threatening outcome of antipsychotic use with a high mortality rate.

Antipsychotic dosing forms are crucial for patient compliance, with options including oral, dissolvable, intravenous, and depot injections.

Chlorpromazine, the first antipsychotic, has a wide side effect profile affecting multiple neurotransmitter systems.

Clozapine is highly effective against schizophrenia but carries a risk of agranulocytosis, a potentially fatal side effect.

Olanzapine is a widely prescribed atypical antipsychotic with a high risk of metabolic side effects like weight gain.

Risperidone is a commonly used atypical antipsychotic with a lower risk of EPS and potential for gynecomastia.

Quetiapine is known for its sedative effects and is often used in clinical practice for its calming properties.

Ziprasidone is notable for its potential to prolong the QT interval, requiring electrocardiogram monitoring.

Aripiprazole is unique as a dopamine and serotonin partial agonist, used for maintenance therapy and to augment antidepressants.

Physicians should be aware of the treatment strategies and side effects of antipsychotics for managing schizophrenia and psychotic disorders.

Transcripts

we now move on to the next class of

medications the antis psychotics which

as their name implies are typically used

to treat schizophrenia and other

psychotic

disorders antis psychotics are often

divided into two main categories the

first generation or typical antis

psychotics in the second generation or

atypicals broadly speaking typical

Antico work harder at blocking the

dopamine receptor but because of this

they can result in more motor and

neurologic side effects conversely

atypicals have less affinity for the

dopen receptor

but can cause serious metabolic issues

including obesity diabetes and Hyper

lipidemia while the metabolic effects

are more subtle they are no less serious

so don't let anyone tell you that it's

just weight gain people with metabolic

derangements can lose years off their

lives and this could account for one of

the reasons why patients with mental

illness are now recognized to live over

a decade shorter than healthy

controls a quick high yield tip

something that is occasionally tested is

the fact that anticho work on the

dopamine receptor subtype D2 this is

somewhat controversial as second

generation antis psychotics actually

have relatively little activity at the

D2 receptor but remember it for testing

purposes how I remember this is to think

of the D2 receptor as d2r d2r kind of

sounds like dour so you can think of a

psychotic person taking a dour from

reality antis psychotics are at least in

the short term remarkably effective at

what they do however they also come with

a wide array of side effects often in

proportion to how effective they are

which brings us back to the third rule

of neurotransmission with great power

comes great

responsibility the efficacy of

antipsychotics as well as their side

effects largely derive from modulating

dopamine and some way shape or form

because of this it will be helpful to

review the effects of dopamine using our

handy dopamine pneumonic D for Drive o

for psychosis P for parkinsonism a for

attention M for motor I for inhibition

of prolactin n for Narcotics and E for

extra paramal let's go over these one by

one first we'll focus on psychosis

by blocking dopamine antis psychotics

block one of the primary Pathways that

psychotic thoughts including

hallucinations and delusions take in the

brain this scrap illustrates the effect

that five different antis psychotics

have on the core symptoms of

schizophrenia two other cognitive

features that are affected by antis

psychotics also relate to the functions

of dopamine specifically drive and

attention something that people often

get confused about when learning about

these drugs is exactly what

antipsychotics are targeting some

students initially seem to think that

antipsychotics Target only psychotic

thoughts but this is not true anti

psychotics Target all thoughts whether

the patient is schizophrenic or not on

the screen is a quote from a study in

which antipsychotics were given to

healthy controls to illustrate their

effects on people without active

psychosis as one patient put it I feel

slow but not sleepy during the interview

I feel clumsy and I want to finish as

fast as possible it's difficult for me

to explain what is happening to me keep

in mind that this is a healthy person

not someone who is actively psychotic

starkly illustrating the effects of

antis psychotics on drive and attention

next we'll focus on how antis psychotics

affect the body and induced features of

Parkinson's disease it sounds weird to

think of it this way but when you give

your patients an antis psychotic you're

effectively giving them a form of

medically induced Parkinson's disease

with all the motor and cognitive effects

that go along with that this demonic can

help remind you that Parkinson's disease

is an issue of too little dopamine

Parkinson's disease equals dopamine down

as a bonus and we'll go over this more

later you can do a similar pneumonic

with Alzheimer's disease Alzheimer's

disease equals acetylcholine

down this video shows the stereotypic

walk of someone who has been given a

high dose of typical anti-yo which

resembles almost exactly the Walk of a

patient with Advanced Parkinson's

disease illustrating again that patients

on antis psychotics are

pathophysiologically similar to patients

with Parkinson's disease soon after the

introduction of the first antis

psychotic named Thorazine this walk

became known in the medical field as the

thorine

shuffle in which the patient will have a

posture which you'll be stooped over

lean

forward and then we'll have difficulty

as far as initiating gate when the gate

is initiated there are small steps often

times there's a there's a Trier

associated with

this and as the gate progresses there

may be a picking up of speed or what's

called a fenestrated

gate and then in turning instead of

having the normal turning the patient

will turn turn on block which means

they'll turn

almost as a

statue moving

around and then again having difficulty

starting and the marsh Petty

paw next we'll focus on the effects that

blocking dopamine has on the motor

Pathways including a discussion of the

famous anti-y yield extra paramal side

effects extra paramal side effects are

named because they are motor effects

that occur outside of the medular

pyramids while the medular pyramids

involve efr tracts going primarily to

voluntary muscles the extra paramal

tracks involve largely involuntary

muscles there are three main types of

extra paramal side effects and luckily

for you they progress in an easy to

remember order acute Donia hits in hours

aesthesia Waits a few days and finally

aesia creeps up slowly a couple weeks in

remember these well because they still

show up on boards and on Wards even

though first generation antis psychotics

are not used as often these

days acute Donia which can hit in the

first few hours after giving a first

generation antis psychotic often looks

something like

this when when did you start having

trouble talking I'm

critical early this morning and did you

take any

drugs other other than your prescribed

drugs oh no you don't do cocaine or

anything like

that no

okay count to 10 for

[Music]

me okay that's

good

I know I

feel as this video showed management is

with an anticholinergic agent such as

dapen hydramine or badril which usually

results in dramatic Improvement so be on

the lookout for acute distonia as

evidenced by muscles that won't stop

Contracting in the first few hours after

giving an antis

psychotic the second extra paramal side

effect is aesthesia which the patient

may start noticing a few days after

beginning an antis psychotic although

some notice it almost immediately

aesthesia is a constant jitteriness and

restlessness of the muscles which the

patient experiences as being on edge or

feeling the urge to move a lot if you

want to experience aesthesia for

yourself drink a couple shots of

espresso and then force yourself to sit

still if you find yourself physically

unable to do so so and start feeling

restless and jittery you're on your way

to feeling similar to patients with

aesthesia this isn't a minor thing

either and some patients find aesthesia

to be so distressing that they consider

suicide as a way to get away from

it

the third and final extra paramal side

effect is ainia also known as Brady

kinesia this is a decrease in voluntary

movements that usually happens a couple

of weeks after an antipsychotic is

started this shows a person immobilized

standing even though they've been asked

to demonstrate walking this is termed

ainia or without movement although one

can see the characteristic pill rolling

movement of thumb and index finger in

both hands the video we watched earlier

of a patient with a parkinsonian walk

after being given an antis psychotic is

another example of

aesia so putting it all together I like

to remember the three extra peramal side

effects in order as muscle russle and

hustle muscle refers to the contraction

of muscles and acute Donia russle refers

to the rustling movement and

restlessness of patients with aesthesia

and hustle refers to the Thorazine

Shuffle and other decreased movements

characteristic of ainia muscle russle

and

hustle one of the most feared outcomes

of long-term use of a first generation

antis psychotic is known as [ __ ] of

discinesia [ __ ] of discinesia is a

constant involuntary rhythmic movement

of the perioral muscles as we will see

in this

video

I just sit here in

chair unlike the extra paramal side

effects we've discussed thus far which

usually disappear once the antis

psychotic is stopped tar of discinesia

does not always go away so easily and

indeed can become irreversible if it

goes on for too long there's about a 3

to 5% chance of getting tarded for every

year of being on a first generation anti

PS otic so try to avoid long-term use of

these in your patients because of its

irreversible effects on a patient's

quality of life you need to know about

tardive when I hear [ __ ] of discinesia I

try to imagine someone chewing on tar

chewing tardive this video should help

remind you of the chewing

motion his face okay

earli another side effect of anticho use

is hyperprolactinemia

think of the following case study a male

patient of yours that was recently

started on resperidone an atypical

anticho comes in complaining that his

breasts are getting larger rather than

dismissing this as The Psychotic

ramblings of a crazy person take the

complaint seriously as you recall from a

dopamine demonic one of dopamine's big

roles in the brain is to inhibit

prolactin once you start inhibiting

dopamine itself prolactin becomes

unhinged and can cause enlargement of

the breasts even in males one

antipsychotic which is notorious for

this is raridon

you can remember that rise paradon gives

rise to a pair of breaths by pronouncing

it rise

paradon finally we get to one of the

most life-threatening outcomes of

antipsychotic use neuroleptic malignant

syndrome as a bit of trivia to help you

memorize this antipsychotics were

formerly known as neuroleptics which

roughly means grabbing hold of the

nerves as the word malignant May imply

this is a serious event with about a 15%

mortality rate patients with nms often

present with severe confusion agitation

sign ific an hypothermia with a

temperature in the range of above 105°

and muscular rigidity you being a good

clinician and history taker are able to

determine that the patient was recently

started on a typical antipsychotic your

diagnosis neuroleptic malignant syndrome

this video will illustrate how these

patients

appear so it's July

23rd is Brian in the

hospital

been doing this for about 24 hours

now still manages to F his way out of

his restraints pretty good even with you

know just a quick slip not tight on him

he finds a way to loosen it up and then

pull real hard

somehow he's got all four of them on and

he's been doing this all day and all

night and he's still not

tired hey Brian can you look over here

at

me

hi he's got 101 temperature as of right

now he came in the hospital close to

108 pretty much uh cooked his internal

organs and right his

brain

how do you treat nms the answer is

dantrolene a muscle relaxant I had a

difficult time remembering to correlate

dantrolene with nms until I came up with

the phrase Dan never missed a step to

remind me of some dancing guy named Dan

who despite being kind of gross and

sweaty is actually a pretty good dancer

and never misses a step so now we have

Dan correlated with nms or neuroleptic

malignant syndrome alternatively

dopamine agonists such as bromocryptine

can be

used one last note on antipsychotic

dosing forms before we get to the

individual

Antico because patient compliance plays

such a large role in the treatment of

schizophrenia without patient compliance

rates hovering at about 40% the dosage

forms of antiyoy should be addressed

first pom meds are the most

straightforward way but it is dependent

upon the patient being willing and able

to take it regularly which you cannot

assume in this patient

population several Antico have

dissolvable forms available to prevent

cheeking of meds where the patient

pretends to take the pill but later

spits it out these drugs dissolve on the

tongue and are absorbed in seconds which

can help more of the drugs to be

administered but on the downside they're

often very expensive and can only be

given in an inpatient hospital

setting intravenous antipsychotics are

the gold standard as they have 100%

bioavailability by definition but they

can only be safely administered within a

hospital so this is generally used for

acute inhospital management of agitation

and

psychosis intramuscular or IM injections

can be beneficial in severely agitated

patients where IV access is difficult to

obtain in addition there are IM Depot

forms of several Antico which last for

several weeks after injection allowing

for long-term control in patients who

will not or cannot take medications

regularly one important thing to note

when using the depot form of an antic

psychotic is to make sure that the

patient has been tried on the particular

medication first before giving as a

Depot once you give a Depot they are

stuck with it for several weeks so if

your patient is allergic they get a few

awful weeks and you get a malpractice

lawsuit you can remember this using

using the rhyming phrase po before

Depot now we move on to the individual

antipsychotics going over a few high Y

old facts about each let's start with

the first generation or typical antis

psychotics the very first antis

psychotic named chlorpromazine or brand

named Thorazine was discovered back in

1950 chlorpromazine was originally

developed as an anesthetic for use in

the O but it proved unsuccessful in that

regard however it was noted in Trials to

have calming effects on psychotic

patients and quickly came into

widespread use for that purpose today

however it is rarely used because of its

wide side effect profile as you can see

from the neurotransmitters involved

chlorpromazine targets not only dopamine

but also acetylcholine norepinephrine

and histamine receptors resulting in the

wide variety of effects observed

including memory impairment from

blocking acetylcholine hypotension from

blocking dorrine and sedation from

blocking histamine in addition to all

the side effects from blocking dopamine

that we discussed

earlier one high yield side effect of

chlorpromazine that is occasionally

tested is the fact that long-term use

can lead to sediment deposits in the

cornea I try to remember this using the

phrase chloral deposits from

chlorpromazine contrast this with

another typical Antico known as

Thorazine brand named melil in contrast

to chlorpromazine which had chloral

deposits Thorazine has retinal deposits

you are unlikely to see this in real

life unless you're an opthalmologist but

it shows up on board

sometimes hop paradol brand named Haldol

is the most famous of the first first

generation of Antico and it remains in

use today in comparison with

chlorpromazine and Thorazine halop

paradol is much more selective for the

D2 receptor and therefore has less

anticholinergics anti-histaminic or

anti-adrenergic

effects however because it attacks the

D2 receptor so strongly there's a high

rate of extra paramal side effects

including acute distonia aesthesia and

akinesia the muscle wrestle and hustle

talked about earlier in common clinical

practice halap parod dool is sometimes

referred to as whole doll because it is

commonly used for when a patient is

acutely psychotic and needs chemical

restraints hop paradol is one of the

drugs with a Depot formulation allowing

for long-term effects in patients with

only a single monthly injection before

giving a Depot shot however what do we

have to do make sure that they've had

the drug po before otherwise we could

end up with a nasty long-term allergic

reaction on tests you'll need to

recognize that the decanoate form as in

hop paradol decanoate or flu phenazine

decanoate signifies an IM Depot form how

to remember this I try to link the

decanoate with the word decade which

reminds us that decanoate forms last for

a long period of time obviously not 10

years but several weeks through a month

with a complete wash out taking 3 to 5

months while there are many more typical

antis psychotics than the three we

talked about those are the ones you'll

most likely need to know for boards and

Wards let's move on to the second

generation or atypical class of antis

psychotics which as you'll remember have

much less neurologic side effects like

EPS but also have more metabolic and

endocrine side effects such as weight

gain diabetes and hyper

epidemia the first of the atypical

anticho that we'll go over is clopine

brand named cleril clopine is routinely

regarded as the single most effective

agent that we have in the fight against

schizophrenia so why don't we use it all

the time clopine has a rare but

potentially deadly side effect known as

a granular cytosis where all of a

patient's white blood cells are depleted

resulting in overwhelming infection and

even death it's about a 1% chance during

the first year of going on clopine but

because of the possibility of death

clopine is never a firstline treatment

for schizophrenia despite its Peerless

efficacy for patients who have failed

two or more Trials of other

antipsychotics however it has about a

60% chance of efficacy if the patient

can tolerate it without developing any

side effects you can remember the

association of a clapene and a

granulocytosis by thinking that you have

to watch clopine closely to monitor for

a

granulocytosis because of these risks

patients who are started on clopine have

to be entered into a registry to keep

track of them in addition a baseline

absolute nutrifil count or ANC needs to

be obtained before starting treatment

with serial anc's throughout the first

year clopine must be discontinued

immediately if the ANC Falls below

1500 so if clopine is effective but

potentially deadly what other options do

we have the next atypical anticho to

consider would be olanzapine or Zyprexa

in a large trial of different

antipsychotics olanzapine was found to

be second only to close aine in terms of

efficacy but without the risk of a

granulocytosis

for this reason olanzapine is an

excellent firstline medical treatment

for schizophrenia and is among the most

widely prescribed of all antipsychotics

so what's the downside as mentioned

before atypical antis psychotics have a

higher rate of metabolic side effects

and orpine is one of the worst in this

regard patients on olanzapine have a

propensity to gain weight independently

of caloric intake I remember this

Association by emphasizing The O Part of

O lopine and thinking about an obese

person think o for

obesity

moving on through the atypicals we next

hit resperidone brand named ridol

resperidone is your bread and butter

second generation anticho with a low

risk of eps but a higher risk of

metabolic side effects so what's unique

about raridon clinically raridon can be

useful because it's on the less sedating

side which can be great in elderly

patients so think rise and shine with

rise spll as stated before raridon seems

to have a higher chance of causing

gynecomastia as well with the pneumonic

rise paradon gives rise to a pair

another bread and butter atypical antis

psychotic is copine brand named squel

copine is similar to resperidone with

the exception of it being much more

sedate in clinically you can remember

this by thinking kopine for quiet

time another atypical antis psychotic

that we will cover is ziprasidone brand

named Geodon what is unique to remember

about ziprasidone Zone has gained some

notoriety for prolonging the QT interval

which is a frequently tested Point what

other drug have we covered that also did

this that's right it was Celexa or

pneumonic selexis using the car

pneumonic can also help us here look at

this picture of a geom Metro when you

think of Geodon I want you to think of a

geom Metro which is a Zippy car like

celexus a Geo also requires us to do an

electroc

cardiogram the last day typical antis

psychotic we'll cover is aapol brand

named Abilify which is one of the newer

antis psychotics on the market it's

Unique and that is both a dopamine and a

serotonin partial Agonist so its effects

are somewhat different in clinical

practice aapip resol does not completely

block D2 receptors but rather locks them

in at about 25% of Maximum stimulation

which can be helpful for maintenance

therapy but rarely works for an acute

psychotic episode where a more powerful

antagonist may be

required one way to remember the unique

mechanism of Abilify is to rename the

drug and Abilify to remind you that it

has two distinct neurotransmitters that

it hits dopamine and serotonin because

of this dual mechanism involving

serotonin and bifi is often used to

augment an anti-depressant so while

prescribing just AER pipol for

depression is not FDA approved

prescribing an anti-depressant and

aeropol could help in the treatment of

refractory cases of major

depression as a final note recall from

the psych MD pneumonic that psychosis

should be treated by a physician trained

in mental health and is not suitable for

treatment in a primary care setting

nevertheless you should be aware of the

common treatment strategies for

schizophrenia and other psychotic

disorders especially since many

antipsychotics have metabolic and

neurologic side effects that you may be

required to help

treat here's a quick high yield review

of the major Concepts and neonics that

we've covered here make sure you know

and understand the meaning behind each

of these or if not you can rewind and

review any relevant

Parts brick time see you in the next

lecture