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
