uh today we will be talking about antipsychotic drugs drugs used in psychosis right before we really talk about the antipsychotic drugs we must know what is psychosis so who will tell me what is psychosis yes psychosis what is psychosis psychosis is psychosis anyone knows more than that psychosis as we are mental disturbances in which there is loss in which there is loss of contact with reality this is very important that psychosis is a group of severe mental disturbances in which the common thing is that there is loss of contact with reality right for example there are some mental disturbances in which your contact with reality is intact right they are not psychosis for example if I get anxious right I have anxiety for long term but patients who are having anxiety they do have contact with the reality they know what are the real things what is the real world right so that is not psychosis right such mental disorders in which you have the contact with reality as a loose group they are called neurosis they are called Neurosis so first of all you must know what is psychosis before we really talk about the drugs right I'm defining them in a very easy way psychosis are more severe mental disturbances in which person loses contact with reality Neurosis is a milder group of mental disorders in which patient has contact with reality for example anxiety is neurosis obsessive compulsive disorders or neuroses phobias are neuroses because people do have contact with reality but when we talk about psychosis this is a very sphere mental disorders right or mental disturbances in which patient loses the contact with reality can you tell me few conditions in which there is psychosis right of course we are going to spend long time to talk about antipsychotic drugs but first we should know what a psychosis psychosis develop as a part of schizophrenia excuse schizophrenia the special type of mental disturbance schizophrenia schizophrenia is called schizophrenia schizophrenia schizophrenia right and there are many more different type of pronunciation right you can also have your private and personal pronunciation I will during this lecture calling it schizophrenia right so schizophrenia is really a scientific mystery and personal disaster so very severe mental disorder right and unfortunately not rare schizophrenia is a very severe mental disorder or thought disorder right patients thoughts are very severely Disturbed patients develop and schizophrenia very bizarre uh uh delusions he may develop perception I mean thought severe thought disturbances thought disturbances very severe thought disturbances in schizophrenia patient develop bizarre delusions you know what are delusions form false belief right which are held by the patient in spite of the evidence to contrary and these delusional ideas should not come from patients socio-cultural religious background again what are religions these are these are form false beliefs which are held by the person tenaciously tightly in spite of evidence to contrary and these ideas should not be originating from patients socio-cultural religious background is that right unfortunately patients with schizophrenia very very severe type of delusions right delusional thoughts are there then they have severe problems with perception also they have hallucinations right what is meant by hallucination hallucinations perceptions without external stimulus the patients who have schizophrenia many of them develop very severe hallucinations especially auditory hallucination especially auditory hallucination they hear the voices which are not there for others is that right two types of auditory hallucinations are very very you can say important in diagnosis number one some of the patients May complain that they hear the voices which are having the running commentary on patients thought and actions you just keep on hearing for example right now you are attending the lecture and you keep on hearing why you are attending the lecture why don't you jump on the board why don't you kick a man behind why don't you roll on the this place you keep on hearing voices or you are writing some and you hear the voice why you are writing are you writing write it more clearly don't write on this page write on the wall why don't you write on the wall of course do you think you will have a normal life and you're hearing all these sound voices so you may hear the voices which are having a running commentary on your actions and your thoughts and second type of artery hallucination which is also very much diagnostic that is when more than two voices are there two or more than two voices are there which are talking to each other and sometimes they are discussing about you for example two voices Carlos may be hearing two voices they're talking about why Carlos has short hair why he does not shave his head right why he does not bring the beard gives the beard why he is attending the lecture why he should not face to the opposite direction of the board right so do you think you will be happy as you will be disturbed by all these things and you keep on hearing isn't it so this is very very severe problems schizophrenia these are severe thought disorders with very severe delusional problems patients may have paranoid delusions that all the time people uh other people are going to damage him or that is why under swear some schizophrenic patients some become violent because they are delusion that other are going to damage them does that right so there are hallucinations auditory hallucinations then they are also having another problem right that problem is about their speech the speech may be incoherent right and there may be loss of fluency in speech sometimes they just offer you a word salad you don't understand what they're saying but they keep on talking the things just like a salad of the different words right so there are severe thought disturbances they are severe perception disturbances they are swear speech disturbances and of course all of them translate into also severe behavioral disturbances many of these patients who are schizophrenic they develop social withdrawal they socially become withdrawn they don't interact much with other people they have their own private world right to develop social withdrawal they lose their all motivations and goal directed behaviors their level of self-care drastically goes down they don't care for themselves for the dress for their cleanliness right this is very sad isn't it it's a personal disaster and not only and they develop severe mood disturbances also many of these patients they develop mood disturbances also or we call it effective abnormalities effect mean mood right effective abnormalities or abnormal effect it is not with e it is a these are one of your spellings where I'm sure I'm right now effect Disturbed effect disturb mood for example either you know normal mood has a range of responses you know you become happy you become sad and it shows certain what intensity of emotions also depending upon your feelings but these patients who are schizophrenic they develop flattening of emotions what is flattening of emotion someone bring air out of emotions flattening of emotions flattened emotions are said to be there when person has person has reduced intensity of emotions and person should be really happy he's very little happy and when he should be really sad there's very little sad for example to schizophrenic patient if you tell that he has lost his uh or his wife has what is this filed for the divorce right he may not be bothered right or if you say there is a he got a suppose Lucky Draw big amount jackpot it may not be significantly happy right their emotional displays flattened right there's no significant fluctuation even emotional the range of mood and emotions may be constructed also right the full spectrum of mood displays not only reduced in the Spectrum and colors but reduced in intensity also sometimes they are so much lost in their world that if you try to talk to the schizophrenic patients you feel that communicating to them is very difficult many psychiatrists uh explain it in this way that psychiatrists say when we talk and try to communicate to a fully schizophrenic patient we feel as if we can see the patient patient can see us because as but as if there's a very thick pane of glass in between the psychiatrist and the patient right what is really meant by the schizophrenia sepulating of the Mind schizophrenia means the plating of the mind right and most sad thing is with all our medical advances yet we don't understand this disease clearly yet we don't know how it really start we have many many theories and hypothesis we will discuss and we don't have any drugs which really Alters the course of disease write down all the antipsychotic drugs are just symptomatic drugs they are symptomatic drugs they don't alter the original disease process yet we are not sure even what is the original disease process right even though there are many theories and hypothesis but antipsychotic drugs are group of drugs which alter the symptoms after this psychotic disease right they don't alter the pathogenic process as such then one more sad thing about it you know it's as common as diabetes mellitus but you see the diabetic patient everywhere you see them less often schizophrenic because families keep them away from you they don't interact diabetic patient will talk to everyone even they keep on mentioning sugar level is up sugar level is down right these complications are there but schizophrenic is not going to talk to you now my dopamine receptor level is up and now dopamine receptor level is down he is not in touch with reality he's not in touch with you right and family is where schizophrenic patients are there they try to keep their patients secluded or away or in some special sport circumstances so they are not really in the much in the community and open in the community like diabetic patients one percent of the world population is schizophrenia is a big percentage one person regardless of religion regardless of social status regardless of economic status and financial status regardless of geographical area one percent of the world population is having seriously and sad things don't end up one more sad thing is you release usually not always but usually this disease start when life should be the most beautiful around the dollar sense you know adolescence's age when you feel you are so strong you can take over the world and you can achieve whatever you want unfortunately one percent of the people around that age develop schizophrenia then one more sad thing we don't have any therapy which cures them there's no cure rarely a patient after the treatment with antipsychotics really become permanently okay most of them develop some residual they have some residual disease or they have recurrent disease or chronic disease so again what is schizophrenia very severe type of psychotic disorder right one percent of the population suffers with it as common as almost diabetes mellitus right the severe thought disturbances so where perception problems severe behavioral problems right and with that patient has severe speech problems and sometimes even motor abnormalities some of the schizophrenic patient developed Catatonia you know what is catatonia not all but some of them these days we see less catatonic because we give antipsychotic drugs Catatonia mean that patient goes to your part assume the particular posture and then maintains this posture for example patient become like this and then remains like this for many many others right they're not only abnormal motor situation in which person assumes the posture and then keeps it for long long time right it is so sad then there are other types psychosis may also be part of some other diseases as I told you psychosis is part of the schizophrenia but it may be part of some other disturbances for example psychosis may be part of very severe mood disorders very very severe mood or effective disorder mood disorders are effective disorders for example person who is extremely extremely depressed or patient who is manic Mania where mood is extremely elated elevated right and many are also and mood is very high some people become psychotic they lose the contact with reality manic patient may be telling you that he is going to buy the stars and distribute to you right or manic question may tell that he's going to buy all the Airlines and provide every African child with one airplane so that he can come to USA and visit you so you know there's something wrong severely wrong with his thought processes right Mania and severely depressed patient extremely depressed patient may also lose the contact with reality and may become psychotic then psychosis may be part of some drug toxicity there may be toxic psychosis some CNS stimulant drugs if you take and large doses they may produce psychosis amphetamines can produce psychosis high doses of levodopa can produce psychosis PCP what is PCP fence cycladine have you heard of it I think they call it angel dust or what PCP that can produce psychosis so psychosis is simply the person loses contact with reality isn't it and classically psychosis seen as a part of schizophrenia but it may be seen in severe mood disorders it may be seen in some toxic States patient develop psychosis or loss of contact with reality so this was something basic about what is psychosis now we start talking about antipsychotic drugs yes please draw the drug yeah the problem will continue no it will reverse in toxic psychosis if you withdraw the drugs which is inducing psychosis most of the time psychosis reverses patient again establishes the contact with reality am I clear now we come to something about that when we are going to talk about the antipsychotic drugs we will discuss that some drugs handle the positive symptoms of schizophrenia very well and the other drugs which also manage the negative symptoms of schizophrenia it means we must know what are the positive symptoms of schizophrenia and what are negative symptoms of schizophrenia right let me tell you what are positive symptoms rather why don't you tell me the positive symptoms of schizophrenia and there are negative symptoms of rather positive symptoms should be really red it's dangerous situation and negative symptoms where patient cool down yeah there are positive symptoms of schizophrenia and there are negative symptoms of schizophrenia it's easy to understand let's suppose this is a normal happy person right unfortunately if this person develops schizophrenia right there are few things which are added to his personality a few things which are added to his personality and there are few other things which are removed from the normal personality when a person develops schizophrenia there's a few symptoms he develop in addition to his normal personality and those symptoms which are developed in addition to his normal is called positive symptoms and the certain features which are eliminated or deleted from the normal personality and then we say those symptoms are negative symptoms let me give you some examples for example if a person develops very severe delusions this is something addition normal person does not have delusions so these are added things added so delusions must be considered positive symptoms if some person is having auditory hallucinations because of Any patient is having auditory hallucination it is in addition to the normal life so it is positive symptom so delusions and hallucinations which are the very florid symptom of the disease are also called positive symptoms of the schizophrenia right and will later on talk positive symptoms are managed very well by the typical antipsychotic drugs antipsychotic drugs are classically divided into two two groups antipsychotic drugs okay psychotic I will explain later why they are in two groups but for a while you just trust me I'm right the antipsychotic drugs are typical drugs typical antipsychotic drugs and atypical anti a typical antipsychotic drugs right typical antipsychotic drugs were initially discovered first they were first discovered in 19 the classically we use the chlorpromazine which we started using in 1960s right so typical drugs typically manage positive symptoms so what you have to remember typical drugs typically manage the positive symptoms is that right like they reduce the hallucinations they reduce the delusions right opposite to that there are some negative symptoms also negative symptoms something missing from the normal personality of the person for example normal person should be social schizophrenic patients are socially withdrawn right social withdrawal it is a negative symptom social with drawal normal person should be motivated in day-to-day life for some certain gains right these patients have lost of motivational Behavior motivational Behavior right and with that another negative symptom is loss of display of emotions display of emotions I told you there may be flattened effect so the normal person is social motivated by the right sense and normal person is emotional is that right actually when severely schizophrenic patients were managed by the typical antipsychotic drugs the positive symptoms went down hallucinations disappeared delusions disappeared but patient was still withdrawn from the society still not motivated to take care of himself or others still patient was not having a prop appropriate emotional display so they said that additional thing of the disease are eliminated but some losses are still there so at that time the term was coined that typical antipsychotic drugs manage the positive symptoms very well but then residual residual disease is still there as manifestation of negative symptoms the beauty of atypical drug is that some of them are significantly effective in management of not only positive symptom but also that's the first point today we learn about the typical and atypical antipsychotic drugs the typical antipsychotic drugs typically manage positive symptoms but they fail to improve the patient's negative symptoms and atypical drugs which are now more modern drugs right they manage not only positive but also to some degree negative symptoms as well is that right yes what's your question oh that's a very important question that why we give still typical drugs answer is the ground realities of life this is let me give you another example first then I will give you the cause everyone loves the most beautiful world woman in the Miss Universe everyone loves but do you think everyone marries a ground reality someone has to marry every type of woman you don't understand it no no okay listen uh Everyone likes every man like the very beautiful and smart woman do you think everyone end up with them no the ground reality is that somehow they end up with the there are reasons they end up with not with those women who are their ideal same as robot woman also they may not end up with the most handsome and most rich man all the time in the same way ground reality about these drug is that this is atypical drug is really very beautiful it manage the positive symptoms it manages the negative symptom it has very less side effects but unfortunately many patients still end up with the typical drugs especially who are treated in the public sector because these are very very inexpensive drugs around reality of their life even psychiatrists know that person who is going to prescribe he knows everything about that atypical drugs are better but still they keep on prescribing under certain circumstances typical drugs because they know that if they prescribe the atypical right maybe patient will never afford it or simply will never afford it patient will become totally mad or psychotic right then human tragedy will be displayed in the house or in the public right so they give the drugs which are typical less expensive the ground reality of life is it clear any more question up to now after this basic introduction we really go to neurological setup that what really happens in the mind and brain of the patient what goes wrong actually basic theory is around dopamine that they believe that patients who are having psychosis or schizophrenia they have increased dopamineergic activity in certain part of central nervous system which is concerned with thoughts and perceptions those parts of the central nervous system which are concerned with thought and perceptions and behaviors right and with social activity motivation right now let me tell you what are those parts let's suppose here is patience Central nervous system and now we'll look for the treasury of course this frontal lobe now what is really believed presently that rather what was the real classical theory that there is excessive dopaminergic activity in certain parts of the central nervous system what are those parts important dopamine energy pathways are related with the limbic system of the brain and especially with the prefrontal cortex you know limbic system of limbic system is what normal function limbic system is concerned with emotions Behavior along with the temporal lobe it is concerned with thought processes it is concerned with perceptions is that right and let's suppose I draw the limbic system here of course it's not an anatomical diagram you just believe it is Olympic system this is this diagram is representing all the structures of the limbic system right which are some component of hypothalamus some component of the uh temporal cortex metalloid body simulate gairas and many other structures let's suppose this is a limbic structure of the central nervous system which is concerned with emotions behaviors thoughts recent memory and along with the temporal Loop function it is concerned with perceptions also actually from the midbrain from the midbrain there are special group of neurons which are having their projections going to the where limbic system and these neurons are yes dopaminergic all of them are releasing what dopamine on the limbic structures these are dopaminergic neurons these group of neurons are neuron you really want to know this area this is called ventral tegmental area ventral segmental area in the midbrain or mission cephalon of course and this dopaminergic activity your pathway or track dopamine energy track this is called mesolimbic tract meso limbic Trend or pathway mesolympic pathway now this mesol limbic pathway is a dopaminergic pathway right which is connecting the mesencephalon with the yes limbic system right the classical Theory which is called dopamine hypothesis which is called dopamine hypothesis according to that hypothesis and I will tell you later what are the evidences for that hypothesis that what's wrong in the disease process that here is increased dopaminergic activity more dopamine is released here right and the neurons in the limbic system they are having here do receptors for dopamine what are these receptors these dopaminergic receptors are specially D2 receptors which receptors D2 receptors receptors are called D2 receptors and D2 receptors are this present pre-synaptically as well as Post synaptically in the limbic system is that right now what is really believed presently that increased dopaminergic activity through mesolympic tract when it is chronically increased that produces the positive symptoms here that produces the delusions that produces the hallucinations right this is increased dopaminergic activity which produces positive symptoms also mesolympic trade now let me tell you something about dopamine receptors dopamine receptors are five types five types of course D1 D2 D3 D4 D5 and if this is one neuron right let me show you how the dopamine work this is one neuron this is dopamine releasing neuron right and this is the next neuron this is presynaptic membrane and this is post-synaptic membrane this is dopamine transmission of course once dopamine is released it will act on the post-synaptic membrane and on the postsynaptic membrane the receptor is seven to seven pass receptor what is this receptor seven path receptors inside it must be coupled with G proteins you know all seven pass receptors are Serpentine receptors are coupled with intracellularly with G proteins and there are pre-synaptic receptor also for dopamine and they're also coupled with intracellularly with the G proteins is that right now so dopamine work postsynaptically as well as presynaptical right now dopamine receptors are classically five types D1 D2 D3 D4 and D 5. now D1 and D2 receptors are coupled intracellularly with G stimulatory they are coupled with g stimulatory it means when dopamine act on D1 receptors or D5 receptors in the Target cell intracellularly G stimulator tree protein is activated which stimulate adrenaline cyclase and that increases intracellular cyclic amp so it means the D1 receptors and D5 receptors are intracellularly once they are activated they increase the intracellular cyclic amp right opposite to that D2 D3 and D4 they are coupled with G inhibitory protein so when dopamine stimulate D2 or D3 or D4 intracellularly G inhibitory protein is activated you know how the gene inhibitory work let's suppose this presynaptic receptor is D2 if this is G2 receptors this is coupled with G inhibitory G proteins are having Alpha inhibitory component right and beta yes and Gamma inhibitory component right when dopamine stimulate the D2 receptor D2 receptor stimulate the G inhibitory the alpha inhibitory will inhibit which enzyme Aden allyl cycle is it will inhibit adrenaline cyclase when Alpha inhibitory will inhibit the adrenal cycle is then conversion of ATP into cyclic amp is reduced this is one result when D2 are stimulated intracellular cyclic MP levels are reduced secondly this beta and gamma unit right they can stimulate potassium channels these are called beta gamma operated potassium channels when potassium channels will open in the membrane potassium is more in the cell or outside the cell yeah cells are the bags of potassium cells are rich in potassium so when beta gamma unit open the potassium channels potassium efflux start potassium a flux start ly beta gamma unit interact with the what is this calcium channels and they block these channels so calcium influxes reduced is that right now let's see what will be the result of on the neuronal activity what are the results on the neuronal activity due to these biochemical changes after dopamine action on the D2 receptor foreign number one again let's start from the beginning neuron is really there is dopamine present on the neuron D2 receptors especially in mesolympic area D2 receptors are present presynaptically as well as postsynaptically right when D2 receptors are stimulated the intracellularly stimulate G inhibitory protein Gene inhibitory protein consists of alpha inhibitory beta inhibitory and Gamma inhibitory Alpha inhibitory inhibitside in allyl cyclists and result in reduced level of cyclic amp when cyclic amp levels are reduced this reduced activation of protein kinase a when protein kinase a activity is reduced in this neuron then phosphorylation of those enzymes which are concerned with synthesis of dopamine is reduced because normally protein cane is a phosphorylate the enzyme which are involved in synthesis of dopamine for example tyrosine kinase enzyme now when cyclic amp is low then protein kinase is low then enzyme For the synthesis or dopamine are not phosphorylated and they become slow down in their action so synthesis of dopamine become plus this is one how there's Auto inhibition by this pathway secondly when beta and gamma unit of inhibitory system activate the potassium channels this heavy potassium e flux cell is losing the cations so cell becomes more electronegative when Photoshop moves out cell become more Electro negative it becomes more polarized to the negative side it become hyperpolarized right so look here if Cell restroom potential was minus 90 millivolt neurons are resting membrane potential was minus 20 millivolt and threshold was minus 60 millivolt threshold potential normally you have to take the restroom and potential up to threshold and then action potential will start all of you know that now when potassium will come out then cell inside will become more negative because it has lost the positive charges so resume Potential from minus 90 it may become minus 95 so it has moved away from threshold so it becomes easy to stimulate or inhabit difficult is that right so in this way it it produces the reduces the action potential then electrical activity in the neuron thirdly you know normally even calcium goes into neuron look when calcium goes into neuron calcium the positive charges when calcium normally when calcium in flux occurs then calcium will take the rest of potential to threshold and increase the excitability of the neuron is that right these beta inhibition gamma inhibitory block the negatively regulate the calcium channels so cations cannot enter into neuron so it is now difficult to stimulate the neurons so what really D2 receptors are doing the D2 receptors once they're activated by dopamine they reduce the intracellular level of cyclic amp and that reduces phosphorylation of many functional proteins and functions of the neuron including the synthesis of secondly it Alters the electrical property of the neuron by leading to the cation efflux well leading to the cation loss that is potassium loss and reducing the cation gain that is calcium so neurons under the influence of D2 action lose the cation and don't get the cations so they become inhabited and dysfunctional am I clear so this is the basic concept in the patient of schizophrenia that what really happens that there is excessive and dysregulated dopaminergic activity in mesolympic pathway and that leads to Disturbed function of the limbic system and that translates into positive symptoms like severe Illusions due to dysfunction of the neurons and severe type of hallucinations and behavioral disturbances as well psychomotor disturbances am I clear now there is another pathway which is equally important there is one more pathway here and this pathway is headed from the where from missions have learned to the prefrontal cortex this is going from mesion cephalon to the prefrontal cortex of course good students know it prefrontal cortex is concerned with your with your personality your personality depends on lot of activity in the prefrontal cortex because the free frontal cortex is damaged with the major personality changes is that right now normally this pathway is also dopaminergic and this is called not mesolympic this is called meso cortical pathway this is called miso particle pathway later on I will tell you how the drugs modify these Pathways to correct that to produce uh alleviation of the symptoms this is mesocortical pathway actually the modern concept is that in a healthy mind there's a balance in these two pathways there's a balance in these two pathway the dopaminergic activity and meso limbic pathway and other Pathways meso cortical pathway right dopaminergic activity in music pathway right this should be balanced to have a normal personality the way you are all of you thank God right you must be having balance in visual limbic tracks and dopam logic activity in mesolympic system and balanced activity in mesocortical now what is believed there's a black box here we don't know what happens here we disturb the balance there I say this is scientific mystery we are not clear what really happens here we know there are some genetic influences right there's a genetic component in inherited component in schizophrenia there may be some environmental factors we are not clear this black box for us that's what Genesis of exactly this disease we are not sure now with all our modern Sciences for we know there is something happening at this level which we yet to be discovered right but that's something reduce increases the activity in mesolympic pathway and decreases the activity in where is the cortical pathway so when limbi mesolympic pathway become overactive you develop the positive symptoms cortical pathway become interactive you develop the negative sentence right because motivation social behavior mood fluctuations all these are strongly related with your personality and prefrontal cortex so what really happens that the one of the modern concept is you know the sad part about the diseases which we don't understand is that every Professor has his own Theory right so one of the theory which tries to explain whole this process is that there is increased dopaminergic activity in mesolympic pathway right and that leads to what yes positive symptoms and probably there is decrease activity in mesocortical pathway and that produces the negative symptoms is that right am I clear and they think in this box Black Box what triggers the disease probably this is not on dopamine but there are glutaminergic Pathways also there I will talk about them later glutaminergic pathway and there are five hydroxide tryptamines Corrections which produce this imbalance now you will be able to understand very clearly that when we give the positive when we give the classical drugs classical antipsychotic drug they are anti-dopaminergic drugs the classical antipsychotic drugs block the D2 receptors is that right and when the block the D2 receptor look here they will block this activity and eliminate the positive symptoms when you give classical or you can say typical antipsychotic drug that typically blocks D2 receptors and when that blocks the D2 receptors excessive activity dopamagic activity is reduced and positive symptoms are managed but of course that is not the way to manage a reduced activity here there is already reduced activity so do you think classical drugs which act by mainly blocking the D2 receptors strongly do you think they can manage the negative symptom they cannot you can enter from this discussion they are more effective in handling of the positive symptoms now let's go back to dopamine hypothesis dopamine hypothesis consists on this thing that in the central of a system Whenever there is excessive dopaminergic activity especially in the mesolympic system that translates into psychosis and what is the evidence there were multiple evidences in the favor of dopamine hypothesis even though still it is considered imperfect hypothesis number one the drugs initially discovered drug which was very good antipsychotic drugs were all d2 receptor blocker they were all d2 receptor blockers especially the typical drugs which were initially discovered there were D2 receptors blockers so doctors knew with their experience that antipsychotic drugs are dopamine receptor blocking drugs so they inferred naturally their psychosis is probably due to increased dopaminergic activity is that right that was One support to the dopamine hypothesis second support to the dopamine hypothesis was that if dopamine hypothesis is true then the drugs which increase dopaminergic activity in central nervous system they should produce psychosis if dopamine hypothesis related with psychosis is true then those drugs which can increase dopaminergic activity and settle another system and toxic levels they must produce psychosis and with observation it was proved right for example lever dopa liver dopa increases dopamine activity in central of a system and in high doses in toxic state produces psychosis then another drug is of course it's not really a drug cocaine cocaine increases dopamine level in the central nervous system serotonin levels in central of a system epinephrine and norepinephrine level in the central nervous system who knows how who is going to tell me how the cocaine were anyone who interested in cocaine and bothered enough to know its mechanism of action how the cocaine works blocks where Syria excellent that's great let me explain what she is saying look all the neurons which release norepinephrine or the neurons which relays dopamine or neurons which are released protonin 5 hydroxytryptamine right you know dopamine norepinephrine in these three neurotransmitter have something common they are originating from single amino acid modification dopamine is from tyrosine norepinephrine is also from tyrosine 50 tryptamine is from tryptophan so all these are derived of single amino acids so these neurotransmitters are called monoamines what are they called monoamines now those neurons which are mono monoaminergic which release the which are dopaminergic or nor adrenergic or shortenergic neurons they are very clever you know first you imagine I love to play with the balls I mean playing ball what I do that I throw the ball to the wall and I don't want to bother much I have elastic and elastic attack with the ball I throw the ball and it comes back then again enjoy the ball and come back and again play with the ball come back this is what these neurons are doing these neurons throw the dopamine and then reuptake this is a special mechanism we take it up back they throw the norepinephrine and take it back throw the photon in and take it back they get the action and eighty percent of the mono minds are reuptaken by the presynaptic membranes are restored for to be reused you understand the biological efficiency are you understanding how these neurons play with the postsynaptic membranes they release the monomial in the reuptake collateral now what really happens these reuptake proteins I'm showing here is a presynaptic reuptake proteins these are mono mine reuptake mechanisms cocaine gets stuck here now you can understand do you think this protein can play now that is what cocaine does it puts its you know stocks itself with the reuptake proteins in monomial energy neurons so neurons release the dopamine but they cannot take it back they release the norepinephrine cannot recapture they release the pseudonym cannot recapture so in these synapses there's increased dopamine logic activity logic activity and certain magic activity is that right and of course if dopamine hypothesis is true an increased drop of energy activity produces psychosis then high levels of cocaine must produce psychosis and it does so that is another sport for dopaminergic hypothesis unfortunately people who favor strot energy hypothesis they also have the evidence from the same cocaine is that right anyway so then amphetamines you've heard of something called amphetamines amphetamine the CNS stimulant you know how they work anyone who knows amphetamines how they work that actually Force The increased release of monoam ions when you take amphetamines in large doses they increase the dopamine release norepinephrine release and certain release and if dopamine hypothesis is true then high doses of amphetamines must produce psychosis and they do and they do so what are the evidence for the dopamine hypothesis evidences mean what are the supportive observations which prove that increased dopamine activity is related with psychosis number one antipsychotic drugs which are typically discovered initially they were all anti-depremonergic number two the drugs which increase in the CNS dopaminergic activity lead to psychosis number three evidence that patient and patient who were not treated with the what antipsychotic drugs on their death when they did postmortem studies on their brain slices of the brain they have found increased dopaminergic activity in increased density of dopamine receptors and limbic system right so pre you can say in living patient also and in postmodern studies also they found that in mesolympic system they were in freeze dopaminergic receptors concentration or density is that right no question then another evidence you know dopamine breakdown into which compound metabolitis homo yes homo homo what homo it's beautiful because h v a homo vanillic acid this is the breakdown product of dopamine they have seen that when they treat the patient of psychosis with typical antipsychotic drugs homo vanillic acid level go down as the patient improves they have seen as a patient of psychosis improves with the drug treatment the homo vanillic acid goes down level the homogenolic acid goes down in CSF in Blood and even in urine that is another sport that when hva levels are going down patient is improving coming out of psychosis so this is another evidence probably psychosis were related with excessive and Disturbed activity of dopaminergic pathways am I clear let's have a break now right so we were discussing about the antipsychotic drugs and I mentioned many times that antipsychotic drugs are primarily divided into two groups typically and atypical right few words about that and then we'll continue with our discussion in central nervous system and do permanent system that antipsychotic drugs anti-psychotic drugs right they are basically yes you will tell me typical which are also called classical right and there are atypical or also called modern drugs right recent drugs now typical drugs classically typically they are D2 adrenergic receptors antagonist antago nest right and atypical drugs because they are not typically working only on these so usually it is mentioned that atypical drugs are working mainly there are five hydroxy tryptamine right two receptor antagonist right this is an answer from an average student that an average medical student will say typical drugs are due to antagonist and atypical drugs are fiber toxic tryptamine that is protonin should run into receptor antagonist the real answer should be that they are also D2 antagonist all antipsychotic drugs are due to antagonist all antipsychotic drugs are due to antagonist typical drugs strongly bind and with the D2 receptors and for longer duration atypical drugs also bind and block the D2 receptors but in a mild way and for transient duration right there so actually a typical drug a very strong Affinity to block the D2 receptor atypical drug have weak they also block the D2 receptor but with weak Affinity the tendency to bind with the receptor and block is for transient time and weekly and in addition to that they are having serotoninergic receptor blocking activity is that right we will see that these Concepts have very big implications not only on the therapeutic actions of the drug but these two concepts are also important when we talk about the side effect profile of the drugs is that right so for a while we'll come back again to discuss the typical and atypical drug differences we'll go back to the how the drugs work in the central nervous system right now I'm concentrating on the typical drugs right we go back to our diagram now few things we have already discussed this was our Olympic system and this was our yes which cortex prefrontal cortex we have already discussed that there was ventral tegmental pathway right and this ventral tegmental pathway was Mido originating this ventral tegmental area it was originating as middle limbic and from similar area nearby there are also origination of miso article is that clear and over activity here we are concerned with positive symptoms and under activity of dopamine system here was concerned with negative symptom no problem up to here right now the problem is this when we are giving the typical drugs and they're blocking the dopaminergic pathways the dopamine logic activity unfortunately not only the block here but they also Block in some other dopaminergic Pathways and produce some other unwanted actions let's see what could be the other actions because when you give the drugs typical drugs they will block the dopamine receptors D2 receptors right but not only the block and the mesolympic pathway but they will also Block in other dopaminergic systems in brain now what are other dopaminergic system a very important dopaminergic system starts from substantial have you heard of substantial right so substantial is present where in the midbrain and mesions have long right an upper part of regions have learned it is having upper and lower both in the midbrain there is substantial substantia has a neurons which are dopaminergic right now dopaminergic neurons also come from substantia right and these neurons specially go to the basal ganglia this I'm making the basal ganglia it's not really anatomical diagram or basal nuclei these especially I'm concerned right now with the putamen and the caudate you know they are very important in regulation of the movements Pathways which are going to yes basal ganglia and which basal ganglia those basal ganglia which are striated which are striated so this pathway is called Nigro striatal pathway what is this pathway Nigro striata pathway these group of neurons which are projecting from substantia to the striatum right which are part of the basal ganglia this pathway is called Nigro pathway now microstrator Pathways very important as a part of extra pyramidal motor system you know motor system is divided into pyramidal motor system and extra perimeter motor system and pyramidal motor system start from cortex and goes down as cortical spinal pathway is that right pyramidal extra pyramidal system is mainly controlled by the basal ganglia right now in the basal ganglia for normal function of the basal ganglia there has to be a very good balance between two activities do from energetic activity and cholinergic activity this is very important concept the Baseline has to work in a normal fashion then within the basal ganglia dopamine energy can cholinergic system should be in balance am I clear now when you give these drugs right D2 blockers dopamine receptor blockers of course they not only work where we want they also work unfortunately on the dopamine receptors and striatum and block those receptors also so it means that when you are giving your typical drugs like chlorpromazine chlorpromazine is a typical drug haloperidol is a typical drug right so when you give chlorpromazine or haloperidol or especially haloperidol very tightly blocking the detour surface right so these drugs block the D2 receptors and D2 receptors are present heavily in the Corpus try atom or they are present in order 10 vitamin or simply they are present in basil ganglia is that right now so it means Nigro striator pathway will be working more or less in the presence of these drugs less actually dopamine will be released by the Nitro striatal pathway but dopamine will not be able to act on its receptors and there will be reduced to pharmacic activity what is there there is reduced dopaminergic activity where yes in the basal ganglia when a patient schizophrenic patient is given typical drug typical drug reduces activity in basal handlia of course when dopaminergic activity is reduced cholinergic activity is unopposed then cholinergic activity is no more opposed by dopaminergic activity because both of them are opposing each other balancing each other when you give antipsychotic drugs typical antipsychotic drugs the basal ganglia to form logic activity is reduced and cholinergic activity becomes unopposed due to that reason it comparatively increases and this imbalance produces problems with the motor system is that right this imbalance of dopaminergic activity and cholinergic activity in basal ganglia which dissolved due to a typical antipsychotic drug right that results in very important and severe motor side effects those motor side effects which result due to this imbalance activity of neurotransmitter in basal ganglia those side effects as a group are called extra pyramidal side effects extra middle side effects epsc Extra metal side effects are the most important side effects one of the most important side effects group of side effects related with antipsychotic drugs especially with the which one typical and here it's very easy to infer that atypical drugs don't bind strong liver D2 receptors so atypical drug do not disturb strongly negro striatal system so atypical drug do not produce significant extra pyramidal side effects so this is a very big difference in typical and atypical the typical drugs typically bind with the D2 receptors strongly and typical drugs produce extrapyramidal side effects with a high incidence but a typical drug right primarily as it is mentioned that it is more blocking the sort of energy receptors but they do block The dopaminergic receptors also atypical drugs but transiently with less affinity so what really happens now listen very carefully that I'm going to draw a circuit here this neuron going over there this is robominagic Neuron and releasing dopamine here and this is the neuron present in stratal system now this is your striatal system connection here negro strital pathway bringing the dopamine and dopamine is supposed to work here is that right of course there's no fun in mentioning it is seven pass receptor right now dopamine is going to work over here when you have a typical drug that will tightly bind here and when it will tightly bind here right now what will be the result first try to understand how dopamine is normally released dopamine is released in two fashions one is the neurons all the time are trickling down a very small amount of dopamine that is called tonic release of dopamine what is that tonic release of dopamine but when action potential come when you want to make a purposeful movement there's a big surge of dopamine relays again listen ing pathway and many dopaminergic Pathways they are releasing dopamine in two fashion number one when neurons are not stimulated by action potentials still they release extremely small amounts of neurotransmitters this is called tonic release of neurotransmitter right so dopamine is technically released also there Plus dopamine is released in heavy amount like a big dopamine surge when you want to make a voluntary purposeful movement is that right if this basic information is clear in your mind let's apply it with the drugs typical drugs tightly bind here so they block the action of the tonically released dopamine Plus this they are so tightly binding there that even when dopamine surge come it cannot displace a drug so this system becomes dysfunctional angular system becomes dysfunctional but when we talk about atypical drug they also bind here but Loosely and transiently they made stuff tonic a little bit but whenever you want to make a purposeful movement and dopamine surge Comet displaces the drug that is why typical drugs have more extrapyramidal side effects and atypical drugs have less parameter LS extra pyramidal side effect another beautiful Point here but here also dopaminergic Pathways release of the dopamine and then the next neuron and this is a dopamine receptor is that right this is dopamine receptor here now listen carefully here is dopamine receptor now presently It is believed that in case of psychosis please listen with your both ears in case of psychosis presently It is believed there is increased tonic release of this system the excessive dopamine energy activities due to Tonic activity now tonic activity is blocked by typical and atypical both are you understanding tonic activity is blocked by the typical and atypical both so what does it mean it means typical drugs and atypical both will be antipsychotics again listen typical drug block D2 receptors strongly at mesolympic system as well as at microstratal system typical drug at both sides bind with that receptors strongly atypical drug also block the D2 receptor along with certain energy receptors but they bind with the D2 receptor Loosely and transiently with low Affinity they bind here with low Affinity as well as bind here also with low affinity now psychosis is probably due to excessive tonic activity of dopaminergic system in mesolimbic tracks should because these receptors are blocked typical drugs as well as their typical drugs both are blocking the tonic activity here so both of them act as antipsychotic is that right opposite to that when you come here typical drugs bind strongly and they block the tonic as well as surge atypical drug May block the tonic but do not block The Surge so here side effects will be more by the typical drugs unless by the atypical drug you know what's so funny that no one asked that why we call one group of drug typical and other cause atypical one reason is that that doctors believed that good antipsychotic drugs should be typically producing extra pyramidal side effect initially when antipsychotic drugs were being discovered they said any drug which is producing extra pyramidal side effect must be antipsychotic so they thought it a typical antipsychotic drug must produce extra perimeter side effect later on they found there were some other drugs which could put they they were not producing extrapyramidal side effect still they were antipsychotic they say these are relative period Then they found one atypical then another atypical and now they're looking for where are more atypicals because they are good for the patients patients have less extra pyramidal side effects am I clear let's come back now we have to talk about what are these extra pyramidal side effects which are produced more by the typical drug and less bada now it depends on about 80 percent of the patient eventually develop some of the extra pyramidal side effect it's a big number percentage now the different types of effects which appear number one is somewhat extra pyramidal side effects are produced acutely by the use of the drug and others are produced by The Chronic use of the drug within few hours of giving the drug thank God only some patient developed a very very acute reaction to the drug and that is called dystonias this tonias have you seen the patient with torticollis you have not seen a patient with torticolas I will show you right now actually sometimes when you start antipsychotic drugs some people within few other days few hours or days they develop severe type of dystonias look here how the dystonia patient become like this and now he cannot make his posture okay I did it too much without drug even anyway so patient become like this or like this I think my dress will be also okay now so these are acute dystonias many patient develop that why they developed a problem like this basil ganglia are concerned with posture regulation also this is a postural muscle snack and back muscles so this imbalance May destroy basically have many areas some are regulating the posture some are regulating the onset of the purposeful movements right some of so the basically have many motor functions in some patients within few hours of giving the antipsychotic drugs especially when antipsychotic drug is given apparently someone comes with very severe psychosis and you give injection of chlorpromazine not of course not all patient otherwise will not use these drugs but some patients May develop acute dystromias is that right what are acute dystonias these are very space positive contractions in the postural muscles right like torticollis now so acute dystonia is May develop Within as early as within few hours right so this is one problem this is extra pyramidal side effect right then some people they don't develop this but they develop a different problem after a few days not few hours but after a few days they develop a different type of problem they develop a kinesia what is your concept of a kinesia did you know Parkinson's disease is a part of parkinsonism actually they may develop Parkinson's like syndrome Parkinson's like syndrome and this may occur within few days Within few days that you have started the drug a patient come patient is brought by the family to you and patient is unfortunately schizophrenia if you put patient on the typical drug and after a few days patient is brought back to you it looks like a patient of parkinsonism you know what is wrong in parkinsonism patient typical disease of parkinsonism Nigro stridential pathway degenerate right and patient develop four in Parkinson's disease patient develop typically echinacea or hypokinesia rigidity and tremors with mask-like face mask like face right now what is akinesia or hypokinesia mean difficulty in initiating purposeful movement person has neuromuscular Junction neurons okay motor neurons are okay motor nerves are okay neural muscle Junctions are fine muscles are also healthy but patient finds difficult to initiate motor movement is that right and that is called hypokinesia or echinacea right so this is seen typically in Parkinson's disease this may be seen due to antipsychotic drugs right the patient is sitting then it is sitting patient wants to stand up patient has the willpower but he's surprised that his system does not follow is that right he is unable to initiate a purposeful movement even in Parkinson's it happened first they find it difficult to walk and if they are walking sometimes they find it difficult to stop because they have to activate another set of neurons to stop the movement did you get it this is very sad so hypokinesia secondly rigidity in the muscle flexor and extensors both become hypertonic and primer hypokinesia is typically due to reduced dopamine activity and tremors are due to unopposed cholinergic activity is that right is so important that in Parkinson's disease if hypokinesia is the real problem you give levodopa in Parkinson's disease never give liver to part of patient with the patient with psychosis and in Parkinson's disease if patient has dominantly tremors you give him anticholinergic drug and if patient has both then you give liver dupa with anticolinergic drugs anyway this is Parkinson's Disease now we come back to our discussion that unfortunately some patients who are on the typical antipsychotic drugs they may develop Parkinson's like syndrome typically akinesia right so they will come to you and they have reduced movement and they have mask like phase what is meant by the mask like phase they are having that Spider-Man mask or what Mass life phase mean that you know when you look to someone his expression little bit fluctuate depending upon the likes your dislikes you or whatever right so doctors are used to this thing when patients come to them their expressions everyone shows some expression which fluctuate isn't it and if you have difficulty in initiating of the movement of the facial muscle can you have fluctuating facial expression no special right mask like phase you are talking to the patient you're asking how are you is like looking like that to you like a toad face you have seen the face of a toad special type of frog they have not been looking at frogs okay anyway so what I'm talking about that these people have told like face or you can say mask face so I remember one patient when we started there was a young man about 22 years old and he was brought to the secretary department and he was having this schizophrenia unfortunately and he was having hallucinations and delusion so he was very much his expressions are too much because he was talking to the voices and he was saying I'll tell you I will fight with you you cannot kill me I mean it was very sad situation we gave him the drugs and after uh three weeks he was brought and he was just like this it was very sad right and we knew it was due to our drugs right so it can easier may appear within few days then there are some patients who develop after a few more weeks and months right another problem and what is that problem that is foreign this is mortar restlessness you know when you're very angry can you keep sitting on the chair you start moving around and you become Restless unfortunately these patients become more restless and as they develop motor restlessness Without Anger right the basal ganglia system is Disturbed and they cannot really keep sitting will be developed and those patients who are not having echinacea right so some it doesn't mean every patient develop any every problem some patient may develop dystonia some other patient may develop echinacea still some unfortunate other patients May develop eccothesia right you can say weeks to months this was days to weeks and this is weeks to months all these are extra pyramidal side effects so patient may developes patients keep on moving their leg or um if you force them to set so they sit and mover like this the Restless right then we come to the last but not the least of very bad side effect of use of what typical antipsychotic that side effect is called tardive tardive mean late slope tardive dyskinesia this highness yeah this kinesia mean disregulated movements which occur in a late phase of treatment they develop over months and years months and years they develop due to Chronic use of antipsychotic drugs and unfortunately because this disease is chronic most of the patients these drugs are used chronically and some of these patients May develop tardiff this kinesia now what are tardive dyskinesia first I tell you underlying problem actually dystonias echinesias and ecclesias they are all due to reduced dopaminergic activity yes increased dopaminergic activity now we are giving antipsychotic drugs dopaminergic activity should be reduced why in this patients there is increased so you have the concept of that if you keep on blocking some receptors for a long time receptors become upregulated and they become tissue becomes super sensitized do you know that okay that's good so what really happens that when you are using ah D2 blockers or typical antipsychotic drugs for long time what really happens that when these receptors D2 receptors are blocked in the basal ganglia for many months and years right then the postsynaptic membrane Express extra receptors and postsynaptic membranes develop super sensitivity to dopamine is that right are you understanding me right it is just like that that a woman who is missing her husband for many years should become super sensitive to his sound hypersensitivity otherwise when you talk too much to your wife you become down regulated especially after the marriage is that right this is normal things everyone knows that right that over stimulation lead to down regulation and under stimulation lead to up regulation so receptors are like you right the D2 receptors when they're blocked for longer time they become super sensitive when they become super sensitive even very small amount of dopamine which is having a chance to work in spite of the drug May produce this regulated movement tardive dyskinesia remember in all first three cases by decreasing the D2 blocker improves the situation here if you decrease the drug transiently situation gets worse are you understanding it again I will repeat for example you are giving the patient code chlorpromazine and due to D2 receptor blocking patient develop these first three side effects if it is developing any one of these side effects you reduce the dose of chlorpromazine extra primitive side effect will be reduced but if you have given chlorpromazine for many months and years and eventually patient has developed tardive dyskinesia it means dopaminergic receptor system is up regulated no super oversensitive in the basal Anglia now when targeted skin is the appearance you reduce the dose of chlorpromazine patient will get worth because some of the upregulated receptors which are blocked by the chlorophromazine they will be also become available for abnormal action is that right am I clear usually still we reduce the dose and another funny usually we still reduce the dose and to calm down the patient we may give diazepam and switch the patient to atypical drugs right internet but important thing is again listen attention please that's a very interesting concept that in first three extra pyramidal side effect decreasing the dose reduces the side effect and increasing the dose if someone has dystonia or echinacea or echothesia due to chlorpromazine and if you increase the dose of chlorpromazine side effect will become less or more it will become more look these side effects are due to blocking of dopamine receptor who is blocking the dopamine receptor chloropromazine for example I'm the psychotic patient you give me chlorpromazine I developed dystonia right if you reduce the dose of chlorpromazine I become better or if unfortunately you are really against me and very bad you increase the dose my dystonia become more severe is that right foreign gets worse and when you increase the dose patients become transiently better because here receptor system is super sensitized when you increase the chlorpromazine for a while patient will become better because if chloropromazine is blocking the D2L surface amateur no problem why you always should look so serious what they call the division developed tolerance so they have to like give a higher no it is not that thing look yeah actually this patient is having excessive receptors and due to that excessive activity of dopaminergic system patient is having Target dyskinesia so you if you give extra dose of the drug extra drug receptors will be blocked so for a while patient will feel better but then he will bring up more upregulated receptor and again get tired of dyskinesia so again this is very important point that in extra peripheral side effects these early side effects are reduced by the drug reducing dose and increase by the increasing dose but tardive disc kinesias are increased by reducing dose and decrease by increasing dose and some people believe that they are almost irreversible problem right now what our Target if this can easier what happens to Patient I've told already and dystonia patient will develop some dystonic feature a kinesia patient cannot make purposeful movement become motor restlessness what happens to patient in tariff dyskinesia Tardis is kinesia the more common in elderly female specialist I of course who are on this drug right now what patient is doing how you know that your patient has tardive dyskinesia anyone have you heard of this term or never heard of it improper movements every improper movement is not hard if dyskinesia many elderly women may make improper movements and they are not they may be some other disease or some other reason anyone who knows Target this is very embarrassing situation especially for the patient family there's some senior female in their family and she's having look these are a choreo ethetide Oral Facial movement right for example it is the involuntary movement the elderly female is sitting do you think anyone like is elderly female in the home and he guests come and she start doing things like that right this is tardive dyskinesia these are involuntary Unstoppable or official movements right lateral movements of the Jaws the smacking of the labs and fly catching movement of the tongue and so many other varieties of movements around this area right so these are tardive this kind is yes am I clear no problem up to this side effects okay right he's asking why these side effects are called extra pyramidal side effects let me tell you very briefly you know that you have a central nervous system right these are lower motor neurons these are lower motor neurons which are going to the muscle right now some neurons come from this motor cortex of pre-motor Cortex right and come to lower motor neuron this is called pyramidal system because it passes through the pyramids of medulla these are pyramidal pathway all other Pathways which are going from higher level to the lower motor neuron are called extra pyramidal pathways now extra pyramidal pathways are from Red nucleus rubrospinal Pathways olivospinal Pathways radical spinal Pathways tectospinal pathway the multiple Pathways which are coming to the lower motor neurons other than the cortical spinal as a group they are called extra perimeter all these pathways are regulated by basal ganglia the under the influence of basin ganglia is the headquarter of extra pyramidal system extra pyramidal system is responsible for three things I hope you are not taking my test in neurology okay thank you so extra pyramidal system has three functions number one posture regulation number two it is controlling the tone number three it initiates it help in initiation of purposeful movement with the pyramidal system because to initiate a purposeful movement you need pyramidal and extra pyramidal both and extra pyramidal especially important in maintaining the tone of the muscle and posture of the body is that right now what really happens that in these all problems any one of these component or in any combination that is Disturbed for example here tone become Disturbed here patients find difficulty in initiating the movement here patient is unable to keep the system rested right again motor movement Disturbed which is involuntary tardisia again patient is having motor programs which are leaking out is that right so all do you think this is purposeful patient is doing with purpose so it cannot be permeable is is he doing purposefully so it cannot be pyramidal it is also not purposefully so it is not pyramidal it is not purposefully it is not parameter so all of these has have to be foreign so all of them as a group are called extra pyramidal side effect amateur right and this is one of the major group of Side Effects by the typical antipsychotic drugs yes yeah he is saying that do these effects occur with the atypical that of an answer is no list of us the reason being that atypical drugs even though initially even look scientists are also learning the way we are learning but they are learning a little bit advance of us actually scientists thought initially that every antipsychotic drug must be producing typically producing extra pyramidal side effects because in the beginning the drugs which were initially discovered more a drug is potent as antipsychotic more strongly it was producing extra pyramidal side effects later on they discovered the drugs which was still antipsychotic but not producing extra pyramidal underlying mechanism which is now discovered is that atypical antipsychotic drug also block the D2 receptors right but the bind with the D2 receptors here very loosely so when you want to make a purposeful movement a surge of the woman come and drug is displaced so drug-induced except permeable side effects are not produced or they are less right just to remember that atypical drugs have less experimental side effect and more weight again many patients still don't like the extra these drugs which are atypical drugs because they increase the weight talk about that thing later any question up to this there's no question now one more serious problem I would love to discuss that is life-threatening complication thank God rare but it happens right that is malignant hyperpyrexia or more commonly that is called neuroleptic syndrome that is also a side effect neuro leptic syndrome what is neuroleptic syndrome let me tell you and then I will tell you how it develops first I tell you how it develops okay this syndrome develops in those patients who are super sensitive to dopamine energy receptor blocking blockage there are some people as you know some of you are emotionally super sensitive in the same way some patient may have basal ganglia which are super sensitive to block it off D2 receptors now a person who is super sensitive to the blockage of D2 receptors sometimes when such patients are given injections usually parental drug but it can occur with oral also they are given antipsychopical antipsychotic drugs they develop very very dangerous type of syndrome what happens in that syndrome all the muscles become strongly contracted rigid that is called Catatonia patient goes into one Frozen position and he may he will hold himself in that position for a long time we call it Catatonia and severe contraction of the muscles number one very very severe contraction of muscles when you develop so much severe contraction of the muscles then what happens you produce lot of Heat in the body produces lot of heat patients start developing the fever plus breakdown of muscles may occur due to severe and prolonged contraction myoglobin as a breakdown product of muscles may appear into urine patient may develop myoglobin urea then there's an enzyme in the muscles which leak into blood creatinine CPK creatinine kinase phosphokinase the kinase so muscle creatinine kinase level cause dangerously high in the blood myoglobin urea starts patient has a very strong contractions of the muscle patient develop autonomic fluctuations blood pressure may become unstable right may go up or may go down heart rate fluctuates with that patients capability to regulate the temperature is reduced because you know temperature regulating Center is in hypothalamus good temperature regulating sentence hypothalamus that also has dopamine receptors if those are blocked patient is unable to regulate the temperature unable to sweat so body is producing more heat and unable to dilate the vessels unable to produce a sweating so temperature goes up and it may go dangerously up so very high grade fever strongly contacted muscles myoglobin urea high levels of CPK in the urine and the blood sorry high levels of CPK in the creatinine kinase in blood fluctuating autonomic nervous system and fluctuating and progressively deepening conscious level patient is going to conscious level is going down patient become drowsy and then patients become even even some of these patients may go eventually into coma and even 10 to 20 percent of patient if not treated may die is that right this syndrome is called neuroleptic syndrome right how do you treat it the first step is don't give any more drug which is the cause of the syndrome that's the first thing don't stay the course right stop the drug number one number two stop the antipsychotic drug number two you give dentro lean have you heard of dentroline Dental in the drug which help the sarcoplasmic reticulum to take up the calcium from cytosol dentroll Lane dendro lean you give the dental Lanes it's very specific drug for this situation it helps the sarcoplasmic reticulum to accumulate the calcium from the sarcoplasmic no from the cytosol of the muscle cell myosin relax are you understanding what I'm saying am I clear right calcium is taken up and restored into sarcoplasmic reticulum that's the function of Dental in with that we can give some dopamine Agonist because this syndrome occurred due to dopamine receptor blockage right and if he is really very high temperature you can do some cooling physical means to bring the temperature down all right so neuroelectric syndrome let me repeat it this is one of the life threatening situation which may develop sometimes thank God very rarely in the patients with typical antipsychotic drugs it develops those patients which are very very sensitive to dopamine receptor blockage it is acute all right no one develop neuroleptic syndrome yeah no no it develops in the early when you are starting using the drug because patient has a tendency to develop neurolactose syndrome right so you will Discover it at the early phase of treatment yes please malignant hyperpyrexia actually malignant hyperpyrexia is a term which is used for any condition in which temperature of the body become very high but malignant hyperpyrexia which is due to antipsychotic drugs typical antipsychotic drug is called neuroleptic syndrome right so again neuroleptics and wrong muscles go into extreme contraction they are injured the release of myoglobin into urine CPK in the blood body temperature goes up autonomic nervous system is fluctuating conscious level fluctuation then start going down right and unrated 10 to 20 percent patient have a risk of death am I clear let's have a break so all this is the cost of reducing the dopaminergic activity in the mesolympic system so that patients should develop the contact with the reality but you are taking the risk for extrapyramidal side effects and you are taking risk for this and unfortunately you are taking more risk we'll talk about that after the break now we continue with our discussion with the other dopaminergic Pathways in central nervous system which may be affected by the typical antipsychotic drugs we have already discussed in antipsychotic drugs reducer dopaminergic activity in the middle Olympic pathway and that is the basis of therapeutic action of the drug that it is reducing the degree of psychosis especially it reduces the positive symptoms we have already also discussed that unfortunately these D2 blocker drugs not only block them with Olympic pathway they unfortunately also block microstratal pathway and that may result in extra pyramidal side effects now we will talk about one more dopaminergic system and the central nervous system and in pituitary relationship you see in this area of the central nervous system this is called yeah hypo th Thalamus here's interior pituitary posterior pituitary and this is hypothalamus right let me draw this hypothalamus in larger way posterior pituitary infundibulum hypothalamus body is that right this diagram I made it here now what really happens all of you must be knowing that in the anterior pituitary there are cells which produce prolactin right prolactin producing cells which are present in interior pituitary they are called Electro troughs so these are prolactin producing cells which are present in the interior prolactin producing cells are always they are always kept technically inhibited until prolactin is required now how how they are kept tonically inhibited basically okay let me make it more clear this is in front of alarm and there is special vascular channels between hypothalamus and anterior pituitary these are hypothalamual hypophysical portal system hypophysical hypothalamic portal system now what really happens there is a nucleus here which is called Arquette nucleus right and this is a neurons and these neurons are dopaminergic they are releasing dopamine and dopamine from these neurons Right comes in through this portal system to the anterior pituitary and there dopamine work on dopaminergic receptors which are present on prolactin producing cells this is normal physiology what I'm talking about right now that what is this area of the hypothalamus it is above the infundibulum this is called Dubrow scenarium now this pathway is called because from the tuberous you know this is tuberous area this is my memory area this is infundibulum and season 3 episode pathway what is called publo in front dibular dopaminergic system in this system arguid nucleus which is present in tubers and erium or lowest part of the hypothalamus the circuit nucleus keep on releasing dopamine and dopamine is brought to the interior pituitary and this keeps the electro tropes inhibited so what is the physiological function of dopamine here that it inhibits the production of prolactin now when you give typical antipsychotic drugs they unfortunately block these receptors as well here and when these receptors are blocked what will happen then what really happens at dopamine dopaminergic receptors are blocked and dopamine is unable to inhibit the prolactin production so there will be excessive production of prolactin so the patients who are on typical antipsychotic drug May produce large amount of yes prolactin that is a big problem now this high amount of prolactin or hyperprolactinemia produces troubles in males and females both right and the females what happen that when this prolactin will act on breast that may produce galactorrhea right number two high amount of prolactin well suppress the FSH and LH production so FSH and LH will not be produced enough to activate the ovaries and of course when follicles are not developing an ovary graphene follicle is not formed corpus luteum is not formed estrogen and progesterone is not enough uterus is not properly cyclically responding and this amenorrhea right so what really happens that the females on typical antipsychotic drugs May develop hyper proelectinemia amenorrhea syndrome what is the syndrome called hyper prolactinemia amenorrhea syndrome and they become infertile of course even or a female and she is not fertile because ovary is not cyclically responding right to FSH a Latitude because that production of FSH allergies suppressed by hyperprolactonemia so this is one thing that secondly female libido will go up or down libido will go down number one how the female libido will go down a mistake and female libido depends on what on androgens which are produced by female libido does not develop depend on estrogen progesterone libido in male and female in both depends on androgens males have lot of androgens because they produce androgens from testes plus meals produce Androgen from adrenal cortex females produce Androgen only from adrenal cortex that is why female have less they don't get as wild as we get right I don't know it's good or bad but anyway so they have less androgens and those androgens are coming from adrenal cortex is that right so females libido is not decreased significantly uh but the good point is that they don't get pregnant right it's good for the psychotic female or bad that's good a female who is having schizophrenia and she's into treatment it's not the time to get pregnant and have a baby and raise the baby she's not fit for that isn't it so this side effect may not be that big side effect for female but anyway she developed hyperprolect anemia with amenorrhea infertility libido may not be affected that much but when we come to a male patient who is schizophrenic right when he is on typical antipsychotic drug he also developed hyper prolactinemia and with that he may develop gynecomastia of course he's not very proud of that secondly uh male although developed decreasing libido right because when males also have high level of prolactin that will suppress FSH allergy release and that will reduce the function of FSH LH are gonadotropic hormones not only stimulate the ovaries but in male they also stimulate so when testicular function goes down so naturally meal also become infertile and this reduced libido and there is uh do you think it's good for female to have significant reduction in libido or not when he is psychotic it's great that he should have reduced libido otherwise he will be causing tragedies around here and there and he may be a source of big troubles himself right so males develop reduced libido gynecomastia infertility and another problem which is we are not sure why it occurs many of these patients on these drugs have weight gain right weight gain is one of the important unwanted result of antipsychotic drugs right now we know that these drugs are dopamine receptor Blocker we know how they act on the meso limbic system system and eventually increase in prolactin relays right another thing very very interesting that even though in female this hyperprololactinemia amenorrhea syndrome is good in one way that she is not going to be pregnant but pregnancy tests become positive isn't it funny that female who is an antipsychotic drug she is not going to be pregnant right because she is even Eric but pregnancy test become positive false positive it should be false positive high level of prolactin right that gives pregnancy test positive right so but this is false positive that is the good news right then we come to other dopaminergic system which other dopamine Energy System is there system is here in the chemo trigger Zone you know there is something called Force ventricle you know that right and fourth ventricle this is final okay this is in the middle line the floor of the fourth ventricle here is a special area which is called chemo trigger Zone neurotransmission is also dopamine independent the neurons in chemo trigger Zone you know there is area post trima the fourth ventricle there's over area post trima where Blood band barrier is broken where blood vein barrier is broken so neurons here are exposed to many constituents of the blood and if there is some noxious substance present in the blood that may produce the feeling of nausea here and vomiting right nausea and vomiting so because this this area is triggered by the chemical substances so it's called chemo trigger Zone it's sensitive to carbon dioxide level also but anyway the schema trigger Zone has lot of neurons which are dopaminergic neurons so when this chemical zone is stimulated by some noxious substance dopaminergic neurons fire and produce feeling of nausea and they may start the vomiting also and the good news is that that these antipsychotic drugs also block the performance receptors here and down regulate the activity of reduce the activity of so these drugs can act as antimatter drugs that is a beneficial action right one of these drug promethazine is used as anti-immatic drug is that right so what did we learn up to now let's sum up let me draw a diagram related with the what is it I think you need some ophthalmologist what is this this is antipsychotic drug typical typical anti psychotic drug right now with this domain with this domain it can block what dopamine this is D2 receptor blocker is that right this domain because this block the this component of the molecule this blocks of dopamine receptor we already know we have discussed so many time it has good effects and bad events right while our good effect is antipsychotic action and and say yes please psychotic action and NT automatic action and bad effects are extra perimeter side effects yeah increase prolactin these two problems right so basically this part of this finger this domain of the drug this is dopamine receptor blocker right then unfortunately this drug typical drugs have unwanted domains also there some other unwanted domains for example this domain this domain blocks Alpha adrenergic receptor and if it blocks Alpha hydrologic receptor it is of unwanted action when you give someone typical antipsychotic drugs like chlorpromazine let's suppose this is chlorpromazine right typical antipsychoticator so it will block the Alpha One adrenergic receptors now what is the normal function of the Alpha One adrenergic receptor it has many function but at least you are supposed to know two functions one is that Alpha One mediated vasoconstriction it is a vasoconstructor drug and uh for one receptor is vasoconstructor number two alpha 1 receptors help in male ejaculation you know erection is parasympathetic activity and ejaculation is sympathetic activity mediated by Alpha One adrenergic receptors is that right now when you give someone drugs like typical antipsychotic what they will do they unwantedly they may block some of the alpha 1 receptors in the body so when vascular alpha 1 receptors are blocked that may produce hypotension hypo tension postural hypotension right and many of these patients when they develop postural hypertension we have to give them fluids saline at least to bring their blood pressure back postural hypertension is one of the side effect of unwanted of course section secondly in males and some of the male alpha 1 receptor blockade may lead to ejaculatory failure literary failure and I think many of them don't mind that much because already the little bit is less and they are less action right but if there's some action then they will develop ejaculatory failure some of them due to Alpha One receptor blockage right then you see it has additional fingers and additional actions which are again not wanted actions for example due to this domain it can block muscarinic receptors of course these are called Energy receptor and do you think it's a good news or bad news for the patient it's a bad news especially for elderly patients right why because when muscarinic receptors are blocked then a style choline dependent activities are inhabited especially astral choline dependent musculinity activities are inhabited do you know what are those activities can you tell me number one central nervous system has cholinergic receptors you know cortex has called Energy receptors cerebral cortex oh yes and collagen cholinergic pathway here throughout the cerebral cortex help you for two things number one orientation you are aware of right now you are aware of self and the surrounding you are aware of you are well oriented and time place in person is that right those neuronal circuit which makes you aware of time place and person what is the time what is the day what is the year who you are who are the people around you where you are right all these things there is your well oriented time in time place and person this function is done by cholinergic pathway in the cerebral cortex which are stimulating The musculinity receptors and this drug May block those musculinity receptors and when it may block those musculinity receptors then it may produce disorientation and confusion because patient may not remain well oriented in time place and person and it may produce confusion and plus forgetfulness forgetfulness yeah actually this is a basic principle all the antimasculinity drugs which can enter into central nervous system they produce forgetfulness and difficult impaired memory you can say produce impaired memory with impaired orientation and time place in person am I right how about old people are not happy with this drug they get confused they get forgetfulness whatever little they remember in psychotic State even that may be forgotten and then more sad news are coming you know this is the cholinergic system we drive the git and urinary bladder this is a cholinergic system it drives the restaurants so what really happens of course the muscle of the urinary bladder not gallbladder right now so what really happens then the masculinity receptor of the blood jits smooth muscles are not having enough cholinergic muscarinic stimulation patient may develop constipation and diff even retention of fecal matter do you think old man will be happy with this there's another unwanted side effect right fecal retention and more sad JD is a big volume maybe you can retain some good fecal matter extra the real tragedy is when cholinergic system fail on the urinary bladder due to musculinity receptor blockage and patient cannot urinate and that may end up into urinary retention do you think it's good especially for elderly males they are very unhappy because they may have benign prosthetic hyperplasia that may be already producing some troubles with urination at the top the truth or does not contract due to cholinergic muscarinic failure you must be thinking it's better to have schizophrenia or better to have this drug this drug has lot of side effects right and get story is not over it has one more unwanted domain what is this one this was D2 domain right and this was Alpha blocker domain and this was your muscarinic blocker domain here is system Interceptor blocker domain H1 blocking domain so this drug may also unwantedly block the H1 receptor in CNS and that may produce sedation is that right sedation is good in the beginning when patient is very agitated and Disturbed right so that may be good to relax a patient for the patient some words dated right but in the long run station stays there sedation stays there that may be when patient gets better his functionality may be impaired right so these drugs also produce sedation due to two reason one reason of sedation is hystermen receptors are blocked second reason for station is a sedation is Alpha One adrenergic receptors are blocked because when you are excited the CNS epinephrine norepinephrine is released and when that epinephrine norepinephrine assets use sulfur one adrenergic receptors and if those are blocked for degree of excitement in the CNS is reduced and that adds to station am I clear sure and this finger I will break because this was for what this was to block the energy receptor which is not blocked by typical drugs right what really happens this is a little finger which was for blocking five yes what five hydroxy tryptamine drug right if you what is the difference in typical Dragon atypical drugs you know what is the difference and typical drug this become big finger and all other finger shrink that is it are you understanding in atypical drug lesson this is a typical drug in atypical drug again listen carefully atypical antipsychotic drug this finger become more active this blocks fiber hydroxyltryptamine receptors right and all these histamine blocking screening blocking Alpha blocking activities reduced world news bad news good news even this finger work in a different way it does not work in a very intrusive way to the receptor to block or not in a very you can say strong way it also work a little bit on the D2 receptors that is even good the little bit action on D2 receptors transient action may be enough to produce antipsychosis but may not be enough to produce uh extra pyramidal side effects so let's let's draw the atypical drug here this is a typical drug right it leads to weight again right and little finger is a big fiber or three tryptamine blocker is really powerful but histamine blocker is less what was that my screen is blocking is less Alpha blocker is less and this finger what was this D2 blocker it is really vibrating it's not permanent is moving like this it can be easily displaced is that right I will continue the lecture tomorrow now today we will continue with the rest of the discussion about the antipsychotic drugs right when we talk about antipsychotic drugs all of you know by now that these drugs are basically classified into two major groups yes please what are those two groups typical antipsychotics are classical antipsychotics and I psychotic drugs typical antipsychotic drugs and there are yes modern latest or atypical atypical yes and take psychotic drugs right let's compare and contrast them of course it's easy to understand these were the drugs which were initially discovered and used from 1960s right they was called typical drugs the classical drugs or first generation drugs and these are called These are the drugs which discovered later right and they are called atypical drug or they are called modern drug or we are they're called uh second generation drugs anyway we'll stick with what most of the psychologists call or psychiatrists call typical and atypical drugs now typical drugs typically block visual receptors classically they are anti-doform energy drugs typical drugs are classically anti-dopaminergic drugs specially they block the D2 receptors they write the block the antagonized the reduced section of reduce action at D2 receptors right atypical drug remember atypical drugs classically what we have seen that they block the throat energy receptors 5 hydroxide tryptamine two receptors right they reduce the action on 5 hydrostic term into receptors or we simply call them they reduce the action Act strot energy receptors because they are certain logic receptors blocker but the point which student forget unfortunately is and you have to remember that even though they block certain logical receptors but they also block dopamine energy receptors that reduce the activity at the D2 receptors as well is that right now what is the real difference in D2 receptor activity here and there answer is that these drugs block the D2 receptors yes more importantly and the act on dopamine receptor for longer time is that right they have strong Affinity affinity mean tendency of a molecule to bind with receptor they're very very strong Affinity to bind with the receptors and block them or they have a very very uh potent drugs as compared to that atypical antipsychotic drugs uh if even though they block the certain logical receptors but now it is believed their antipsychotic action is still by blocking dopaminergic receptors but they block the dopamine energy receptors with low Affinity they block The dopaminergic receptors with low Affinity transiently right now why I am trying to stress this thing in your mind the reason being that most important side effect of antipsychotics are related with D2 receptor blockers you must remember that there were lot of extra pyramidal side effects you remember they were extra very the side effects specially dystonias yes yes please dystonias Parkinson's like Parkinson's like syndrome like akinesias and they were echothesias now these extra pyramidal side effects all of them are due to yes anti-dopam allergic activity they are due to anti due to anti-dopamineergic energy activity and yes please at basil ganglia or basal nuclei fine of course one more side effect we add here is straw Dev disc kinesia what is this third if this kind is yes which are long term complication of use of typical antipsychotics but that is due to increased dopaminergic activity dopa menergic activated this is again very important that extra pyramidal side effects the first three side effects which are dystonias parkinsonism and acathesias these are due to excessive anti-doperminergic action excessive super sensitivity of dopamine receptor so that is due to increased job of energy activity now from here we can infer very easily more our drug is potent for D2 receptor blocking action more it will produce extra pyramidal side effects and more successful it will be antipsychotic this was old Theory old theory was that moral drug is potent in blocking the D2 receptors more effective it will be antipsychotic and more not only it will act on the mesolympic pathway but it will also act more potently on the and more ah strong side effects will be seen related with the extra pyramidal thyroid is that right it means that next time if I say one drug is more potent and blocking D2 receptors as compared to the other one then it means the first drug will be having stronger extra pyramidal side effects later on we'll learn remember that when we say a drug is more potent we need its lower dose is that right now opposite to that these drugs their affinity for D2 receptors are less is that right so they produce less extra pyramidal side effects as well but then we we will wonder that if these drugs are ah producing less extra pyramidal side effects how they act as antipsychotic now they believe that their action as antipsychotic agent is because they reduce the tonic action of dopaminergic have two type of activity tonic activity and dopamine surge right these drugs block the tonic activity on the dopaminergic Pathways in mesolympic system by that they reduce psychosis especially positive symptoms of psychosis but because the weekly bind with D2 receptors and basal ganglia so when there is dopamine surge these drugs are displayed from the displaced from the receptor so they don't produce any significant dysfunction in the basal ganglia activity is that right that is why these drugs which are atypical they have less risk of extra pyramidal side effects and this is one yeah this is one good news right yeah that is why now they are considered Superior to typical drugs because atypical drugs uh have less chance to produce or less risk of producing extrapyramidal side effects so now they are considered Superior to what typical drugs is that right again I will I think it's worth mentioning again and again that these antipsychotic drugs which are typical drugs right because they block the dopamine system strongly so they basically produce what problems extra pyramidal side effects strongly is that right but when receptors which have blocked for a long time they undergo what is that upregulation is that right then they have a tendency to produce trade dyskinesia do you think any other side effect or complication is a dangerous complication is produced by these drugs in relation to their action on dopaminergic receptors there's some very dangerous side effect of these drugs that is neuroleptic syndrome I mentioned previously neuroleptic syndrome when we give typical antipsychotic drug to the to a person who is having very very sensitive dopaminergic receptors right you remember that neuroleptic syndrome neuroelectric syndrome neurolactic syndrome even though rare but it is potentially fatal and it is also due to antipsychotic drugs which are typical antipsychotic drugs due to action on The dopaminergic receptors teaching such kind of side effect can be seen with atypical drugs no is that right so how atypical drugs are superior to typical answer should be that atypical drugs as a group how why they are considered Superior to typical drugs simply because atypical drug have less chances and less chances to produce side effects related with the dopaminergic systems the whole group of side effects are eliminated Amic layer no problem but if someone asks and mechanism of action how they are different ah typical and atypical then you will say these are classically blocking D2 receptors they do block classically Photon energy receptors but they also block the D2 or other dopaminergic receptors as well right now let's come to another thing about efficacy of the drugs these drugs are very very effective which are classical drugs or 80 which are typical drugs but atypical drugs are at least as effective as typical or more effective because there are many atypical drugs some of the atypical drugs are as effective as typical ones or some of them are River more effective especially in regard to the handling of negative symptoms now this is very very important information you know there are positive symptoms and there are negative symptoms right actually your typical drugs typically eliminate positive symptoms because typical drugs are considered typically eliminating positive symptoms what were the positive symptoms positive symptoms were due to excessive pathway and positive symptoms were like hallucinations delusions yes what else positive symptoms these are very you can say positive symptoms are those systems symptoms and psychosis which are in addition to patients normal personality the patient has weird thoughts our patient has bizarre delusions or patient has auditory hallucinations right so these are positive symptoms opposite to that there are negative symptoms negative symptoms mean the symptoms which are in a psychotic patient these are the symptoms which I'm missing from his normal personality something is missing from normal Behavior Uh classically negative symptoms include a motivational state a motivational no motivation state there's a lack of motivation there's social yes social withdrawal and what else is there and negative symptoms yes inability to derive player from day to day small activities and hedonia and hedonia this is also a classical feature of depression and he Donia inability to drive player out of small events of the life is that right some people simply call such situation as flattening of emotion flattening of emotions are restricted range of emotion and restricted and reduced intensity of emotional display right so these are negative symptoms again it's worth mentioning that when we were using the only typical drug most psychotic patients they were having reduced positive symptoms but once the positive symptoms are eliminated or reduced prominent symptoms which are left behind are negative symptoms and they have seen that atypical antipsychotics are very effective and elimination of negative symptoms as well right so again what is the real difference in these are typical drugs these two are the typical drugs and these are atypical what is the real difference typical drugs are typically classing D2 receptors blocking D2 receptors these block also energy receptors typical drugs are very very importantly acting on on on D2 receptors so they produce more extra pyramidal side effects and your atypical drugs have less chances to produce so they do not produce extra peripheral side effects then typical drugs typically eliminate positive symptoms atypical drugs eliminate positive symptoms as well as negative symptoms is that right and what do you think that when you are going to use drugs weight of evidence will go to which side typical or atypical yeah this is very important he's worried about the patient's financial background this is very true that's true why still typical antipsychotics like chlorpromazines are Jews the reason being they are inexpensive is that right and atypical drugs are more expensive but a patient can afford an atypical drugs are considered Superior over typical drugs and not only the weight of evidence is in the favor of that rather they also add to the weight of the patient right this is one of the major one of the very important side effect of atypical drugs that patients start putting up weight and many of them stop the drugs for that right once they are out of psychosis of course am I clear weight gain is more seen with the atypical drug as compared to the typical drugs typical drug may also lead to some weight gain but weight gain is more seen with the atypical drugs now let's talk about some typical and atypical drugs let's name them a very important group in case of a typical sorry in case of typical drugs is yes very important group there are three important group one is phenothiazines pheno thyrozenes first group second group is yes second group is tiles and things IO then teens and third group is third group is o a butyrofinance phenons right now phenotiazines are further classified into three types the aliphatic chain aliphatic mean open chain lymphatic chain drugs right aliphatic chain drug and pipe paradine and piperazine group these are ring and piperazine we are supposed to know at least one drug in each group here the drug is which you are supposed to know as chlorpromazine have you heard of it Chlor chromazine which is very commonly is used right chlorpromazine and piperidine group we have thyroidism here it is radazine and in case of piperizine we have flu phenazine flu fena Zane these are the three important drugs there and in case of thousand things the drug is thiotexene thiotexing and buterophenone another very important drug hello have you heard of it hello now few words about everything first of all chlorpromazine this is one of the very commonly used inexpensive drug most of our discussion about the typical drug was actually relevant with chlorpromazine right chlorpromazine is very widely used especially in uh patients who are less affording financially there are few points related with thyroidism thyroidism has three important points to be discussed number one thyroidism is a very strong anticolinergic action anti Cola nergic drug do you think it's good for the patient or bad it is good the reason being that all these drugs are anti-dopaminergic and you remember we have to keep a balance in basal ganglia right all these drugs again all this typical drug there is dopaminergic activity here and cholinergic activity here this has to be in Balance when you give typical antipsychotic dopaminergic activity go down and uncompensated increase action of cholinergic plus decreased over managing action produce extra pyramidal side effects extra pyramidal side effects are produced by reduced dopaminergic activity plus due to uncompensated increase action of style choline so what really happens when you use the thyroidism not only it block the dopaminergic activity it also reduces activity so there is no significant imbalance in basal ganglia neurotransmitter business the result is result is decreased extra pyramidal side effects so actually when patient has severe extra pyramidal side effects due to other drugs in the typical group either you'll switch to the atypical antipsychotics or if patient cannot be switched to the atypical anti-psychotic due to maybe Financial reason then you should choose within the group of typical patient who has a high tendency to develop extra perimetal side effects you will choose the drug they are very strong anticholinergic effect that is beneficial in keeping the extra pyramidal side effects low but of course anti-colonergic action increases the chances of urinary retention fecal retention and anti cholinergic action also produces malfunction of accommodation you know there is a muscle in the eye which is responsible for adjustment of the lens cellularis muscle so ciliaris muscle is receptors they are blocked so actually a patient may develop due to loss of accommodation function patient may develop blurring off VN so many patients who are having any type of drug with strong anticholinergic action they have a tendency for blurring of VN due to cycloplegia cycloplegia is a term which is used for paralysis of ciliaras cycloplasia so even though they are reduced by thyroidism there is reduced you can see extra pyramidal side effect but this increased tendency for blood V and there's increased tendency for urinary retention and fecal retention of course this drugs are not very good for elderly males especially right of course if there is anticolon energy action in central nervous system especially in cerebral cortex that may produce reduce memory and confusion anticholinergic drugs produce confusion when they act on cerebral cortex cholinergic system write another thing when anticologic action is strong on the heart that will produce yes cardiac arrhythmias autonomic control of the heart goes out of disturbance so patient with thyroidism have higher risk of developing cardiac arrhythmias the only good point is that they have reduced extra pyramidal side effects another special thing thyroidity it produces some complications in the eyes they may produce some pigmentation of retina and eventually May produce retinal dysfunction now we come to the next group flu phenazine the best point about fluffenazine is that it is available in dipoform it is available in Depot form right fluffenazine Deco no 8. right this compound is available in Depot form that if you inject in persons intramuscularly just keep on working for three four weeks so this is a very good drug when you want to give to a patient a psychotic patient who is not compliant to the drugs many patients it's very difficult to give them chlorpromazine three times a day they are not taking the drugs they are not Cooperative so what you do that once in a month you get hold of them and inject them right and then for the rest of the month drug keep on working and then after three or four weeks you again get hold of them and give them one interest shot off in order to explain yes he has asked a very good question actually if a patient is on the typical antipsychotic drugs and at the top with that he develops extra pyramidal side effects especially dystonias Parkinson's like echinaceous and echothesias all these are due to excessive anti-doperminergic activity these are all side effects due to excessive anti-dopaminergic activity so we can give them anticholinergic drug to produce some balance in basal Anglia and those anticholinergic drugs are benztropine right those drugs can help you to reduce extrapyramidal side effects except thyroidism and others we can use that but you remember that may produce confusion urinary retention fecal retention and blurring of vision side effects but we can use them but remember one thing some side effects which are produced by excessive dopaminergic activity those patients you will not use anticolor energy for example a patient who developed tardive dyskinesia right was an antipsychotic and he developed rdf dyskinesia they are having excessive dopaminergic activity if you unfortunately if you give them anticolonergic right then what will happen Target if this candidate will get worse is that right okay let me explain this concept that side effects are two types of side effects except on motor system by these drugs some drugs which are due to increase and T dopa menergic activity and other group of side effects are due to increased dope of energy activity dopa menergic activity now side effects which are due to increased drop of energy activity and due to increased anti-dopaminergic activity these side effects will be reduced with anti by these side effects will be reduced by given anti cholinergics you can do excessive anticologic activity to keep the balance but if some say these this side effects are like this this kinesias Parkinson's like problem then dystonias and uh ecclesias but if someone has some complication which is due to excessive dope of energy activity for example dyskinesias or neuroleptic syndrome neuroleptic syndrome is acute excessive response to dopaminergic blockage is that right and Target dyskinesis when you use the drugs chronically and eventually patient develops hypersensitive receptors kinesia is a motor dysfunction which is produced due to increased job of energy action due to super sensitive receptors in those cases you should not use anti-col energy because high at the top you use anticolinergic what will happen imbalance in these patients what you will do you will reduce the what you will do if you use the dose of antipsychotic drug in these patients patient will get worse at least transiently because what is happening they are having excessive dopam energy activity and when you reduce the dose of antipsychotic drug it means you are reducing a dose of anti-doperminergic drug s right so this patient should be switched to the atypicals that's good right with that we give diazepam actually another interesting thing a very important concept is that one patient has and other patient has let's suppose I have a patient here who has a kinesia or dyskinesia uh dystonia or echothesia or Parkinson's like situation or right all these are due to excessive dopaminergic Blockhead is that right and we have two patients they are one patient there who has started dyskinesia now response of these patients into changing the dose of antipsychotic if antipsychotic dose if you want to because here is this all these problems are produced due to excessive block of the dopamine receptors so if you reduce the drug patient will become better this group of patients wear extra pyramidal side effects of Motor problems are due to excessive blockage of dopaminergic system when you reduce the dose the drug patient will get better but there the entirety of discouraged yeah patient has a side effects due to productivity kinesia due to excessive energy activity so in them if you reduce the dose patient will get worse at least transiently or if you increase the dose patient get better for a while so response to the dose change is different and first group of patient and second group of patients again patients who are having dystonias if you increase the dose patient gets worse if you decrease the dose patient gets better claro over to that patient who has started dyskinesia if you increase the dose patient gets better because increasing dosement excessive domestic activity is being blocked by the drug but if you decrease the dose at least transiently patient gets worse is that right okay so we were talking about flu fanazine an important point was it is available in day performer also now we come to the LA about haloperidar is very very important potent mean what even at low doses it blocked the dopamine energy due to receptors very effectively so you need high dosage of this drugs secondly the extra pyramidal side effect frequency and intensity increases with potency of the drug as drugs become more potent in blocking the due to receptors it become more potent to produce antipsychotic action and unfortunately it becomes more potent to produce extra pyramidal side effects are you understanding me so haloperidol is very effective but the sad part is that that frequency and intensity of extra pyramidal side effect without is very high because not only the block the D2 receptors in the mesolympic system effectively but unfortunately they also block the due to receptors in the also very very effectively am I clear so we can say it's very very potent drug haloberry doll and result will be what logically it will lead to more and more extra perimeter side effect and good news is that it is also available in depoform right now let's talk few words about atypical drugs right we have already discussed atypical drug not only block the D2 receptors but they also block fibroid oxy tryptamine receptors group two atypical drugs of course because they bind the D2 receptors with less Affinity so the chances of producing extra pyramidal side effects are less right and they are as effective as typical drugs or even some of them are more effective than the typical drugs and classically they are very useful in case of negative symptoms not only positive symptoms are eliminated but negatives are also eliminated now the drugs which are in that group one drug is clozapine closer pain right I think I should draw with it what does it tell you very very toxic drug look it's very effective drug uh we still use it but unfortunately it is a small but definite risk of very fatal complication that is a granulocytosis in one to two percent of the patient and one to two percent of the patient who are on clozapine right especially you know stem cell divide into mylet stem cell and lymphoid stem cell then one of the myeloid stem cell is going to produce granulocyte granulocytes are classically your three drugs sorry three cells neutrophils xenophils and base of Health actually closer pin has a high tendency to destroy the granulopoises and one to two percent of the patient and if granulocyte number goes down in the blood right that may produce very severe infections right patient may not die of psychosis or patient may definitely die of severe IGN so what we really do that any patient who is prescribed or put on closer B in have for first six months of the treatment every week we do blood counts every week we do blood counts because if granocyte numbers start going down we should withdraw the drug and in early stages usually it is reversible was the right at least for six months and after six months they may do it every second week or every third week right so close up in is very good drug it can block the receptor D1 D2 D3 D4 D5 plus it can block five hydroxyltryptamine receptors right but with all that thing it blocks your bone marrow granular places activity especially in one to two percent of the patient then another drug is olenzapine or lanzapine remember remaining a typical drug do not produce bone marrow toxicity right olenzapine is a good drug because it is useful in so many things not only it is antipsychotic yeah it is also empty anxiety it is also anti depressants it is also anti-depressant and it is anti-manic and surprisingly it is also effective in OCD obsessive compulsive disorder I think some of the entire world especially some of the psychiatrists who don't know how to differentiate the different diseases they can any person come with some psychiatric problem maybe it's a very wrong way to practice putting them on a lanzapine all right so that anything is there will be carried because if patient is psychotic get benefit from length of being efficient anxiety is still getting better if patient does depression still getting better if patient is anti-manic still getting better even patient with OCD obsessive compulsive disorder also get better remember about all these antipsychotic drugs they take few weeks to start their actions they take few weeks to start their action bad thing is that many of these drugs start their side effects first and effects later this is the sad part of the story right anyway so I was telling you Lanza pin should be remembered as it has many you can say action on many different type of psychiatric disorders then there are similar drugs like quetapine zebra sidon beta pin zebra sedon has some problem it can produce cardiac arrhythmias because the president produces prolonged QT interval QT interval means you know this is yeah from beginning of the cube wave up to the end of the T wave actually the prolong the duration of action potential right by blocking the potassium e flux when potassium channel is going to bring the potassium out then naturally uh repolarization becomes delayed so QT interval is prolonged again UT interval is the duration between from the beginning of the QRS complex up to the end of the T wave what really happens many drugs not only is the proced on many drugs prolong the QT interval how they prolong the cute interval actually the drugs which are QT interval per longer they basically block the potassium efflux during depolarization state and when potassium cannot get out of the myocyte myocardial cells potassium coming out is slow so repolarization is delayed because repolarization depends on potassium e flux right so when repolarization is delayed total though so naturally then T wave will be appearing delayed so QT interval is for long is that right and when QT interval is prolonged that increases the risk for ventricular tachy arrhythmias the special type of technology which are produced we call them torsadi pons have you heard of torsadi pants have you heard of them Thor's third set D pointers but it is French word so we read it so actually any drug or any inherited disorder of the channels produces prolonged QT interval that has a tendency to produce a special type of a rhythmia which is called torsadi plant or the tors what is twisting of the points which points twisting of the point which points rest don't tell me wrong things yes twisting of which points points of Q are as complex and these areas what really happens patient has foreign like this then suddenly they become like this then again coming like this like again coming like this this type of you can say ECG pattern CNA ventricular area of course right these are typically seen when uh production channels are dysfunctioning those potassium channels which are responsible for potassium efflux for repolarization and many drugs block these potassium actually if you remember antiarismic drugs there's a whole group of antiarismic drugs which are potassium channel blockers all of them have a tendency to prolong cute interval and all of those drugs have a tendency to produce is one of that then there is another drug that is in this group Risperidone risk paradon right then there is malindon molend on Mullen don't remind me something melindon is a drug which is favorably used in patient with okay I will tell you the clinical situations you tell me what's wrong usually this is small children as right and they are having motor attacks you know motor tax the motor text with obscene language and obscene gesture Tourette Syndrome correct have you heard of Tourette syndrome you never heard of it okay Tourette syndrome is a situation actually where there is a neurotransmitter dysfunction in basal ganglia especially in chordate nucleus right in coded nucleus uh coded nucleus is one part of the basalingalia of course concerned with your motor movement and chordate is also concerned with your emotionality now it is discovered right so what really happens that they have inherited defect in neurotransmission business and quadrate nucleus right and these children right they have motor techs right purposeless motor repetitive purposeless motor activities and with that they communicate with obscene language and obscene gesture for example if 22 year old boy is talking like this we may think testosterone is doing something big but if there's a eight-year-old boy doing or too much obscene language and everything he has to explain by special type of gestures I think you understand use your imagination so maybe he needs some drug like Moline down and they have seen that when they use the melendone drugs uh they calm down and their ticks go down and even their hyper uh obscene gestures and vocal tics all those go down is that right is effective there then another drug is all and there's something special about that Eddie pepper Zone this is one of the latest NT uh atypical antipsychotic drug and it is a very different type of mechanism of action it is partial Agonist on D2 receptors and partial Agonist on fibroid osteopamine two receptors it means it partially stimulated and partially blocks you have the concept of partial Agonist and full Agonist and antagonist do you have concept it's fine if you don't have I will explain in two three minutes yes do you have a clear concept what is meant by the antagonist Agonist and partial Agonist I explain a little bit okay it's a very simple diagram I'm going to draw let's suppose this is a cell these are okay these are different cells with different receptors and we see Mac action of the drugs on them let's suppose this is a receptor here right now look and this is a drug here okay a drug should be different color now this is a drug here would bind with this receptor when this drug bind with this receptor this receptors give let's suppose these four signals then now listen binding of the drug ability of our drug to bind with the receptors called affinity the ability of a drug to bind with the receptor is called affinity and ability of a drug to stimulate the receptor is called intrinsic activity if a drug binds with a receptor that is called affinity and if drug bind and then stimulates receptor that is called intrinsic activity now this drug is having Affinity Plus intrinsic activity affinity mean it has a capability to bind with the receptor and after binding because it stimulates the receptor and scepter has displayed its signaling mechanism it means that not only it bind but it also activates the receptor so this is a drug which is Affinity Plus intrinsic activity such drugs are called Agonist drug what are these called Agonist drug and if they can bind and stimulate it fully we call them full Agonist full Agonist clear now let's go to another example this is the same receptor now another drug comes it has also affinity but its intrinsic activity is half than the this is drug a this is drug B is that right drug B lead to still stimulation of the receptor but less and it does not allow suppose drug a to work it does not allow is that right now in this case we'll say drug B is having Affinity with partial intrinsic activity because it is not producing the full action full action is produced by a these producing partial Activation so we say it is Affinity with partial intrinsic activity such drugs are called partial Agonist what they are called partial yes Agonist they are also called partial antagonists because they antagonize the action of the full Agonist this drug does not allow the full Agonist to work so their partial Agonist and partial antagonist is that right for example again let me tell you if this is your essay node if this drug is drug a is like norepinephrine a friend takes your heart rate from 60 to 100. norepinephrine is taking your heart rate 60 to 100 now another drug come which bind they are is that right and heart rate is from 60 to 80. so it is acting like partial Agonist but now you give norepinephrine can norepinephrine the presence of this drug can you take 200 no so there it will act in the presence of norepinephrine as partial antagonist is that right am I really clear look for example lesson it's a very funny example let's suppose you are standing there someone comes and put you two cakes and you give two cries maybe that person has full Agonist then another friend come unfortunately put you one cake to you you give one cry what do you think what is that partial agonists at least he got some action from you one cry but this single kick person does not allow the other person to put a double cake to you so at least you antagonize those cruel people is it right and there's another friend who or other girlfriend I should say just hold and protect you but no action it is sad but still better than kicks is that right so what is that antagonist right I hope you understand or not yet okay that's good so we come to third situation here the third row come it does bind here and here but does not bind to those point where stimulation could occur so there is no intrinsic stimulation so there is Affinity but no intrinsic activity so this drug is antagonist why because it does not allow the full agonists to work in the presence of this drug full agonists cannot have its section is that clear now so what really happens full Agonist is a drug which is full Affinity with full intrinsic activity partial Economist which has full Affinity but partial intrinsic activity antagonist drug which has full Affinity but no intrinsic activity all right what is this um antagonist drug am I really clear to you guys have you okay if you really are interested to learn there's another term which is used reverse Agonist okay that I will teach you in somewhere else there is another term use Agonist antagonist have you heard of Agonist antagonist truck especially when you study opiate drugs some opiates are strongly against some opioid drugs are antagonists some drugs are Agonist antagonists and don't confuse Agonist antagonist drug with partial Agonist or partial antagonist look actually opioid receptors are five types if a drug come it stimulates two receptors and block three so it is agonistone two an antagonist one three it is Agonist antagonist again listen these are five five receptors if a drug comes bind with all of them and stimulate them fully what is that Agonist another drug come which bind with them but partially stimulate all of them what is that partial Agonist for example also all of them are these are dopamine one receptor dopamine two dopamine three four and five drug which bind with all the permanent receptors and stimulate all of them fully this is full Agonist drug which bind to some of the uh bind with all the dopamine receptors right or even bind with some dopamine receptors but it does not bind at all with others but mind with some and stimulate partially it is partial Agonist or drug with bind with all of them and do partial stimulation still partial Agonist clear or in the presence of full Agonist partial Agonist work as partial antagonist and the presence of full Agonist partial agonists work as partial antagonist because they prevent the action of the full Agonist am I clear then we come to another drug group of drug which bind with all the receptors but this do not stimulate any one of them what are they antagonist they have Affinity but no intrinsic activity now we come with another drug to stimulate two receptors and inhibit other receptors they are against antagonists am I really clear no problem why I explain this because up to now I was telling that all the drugs which we have discussed except the last drug all the drugs were blocking the either dopamine receptors or they were also blocking the fibroid receptors so all of them were antagonist is that right but when I talk about the last drug which was which was ariprazole what was that I said this is partial Agonist to D2 receptors and aripiprazole is partial partial Agonist to fiberocetamine receptor so it means that they are like this drug aripiprazole they bind with the dopamine receptors themselves they produce some action but you don't allow the dopamine to produce full action is that right so adiprazole is partial against or also partial antagonist they have found this drug has also antipsychotic action is that right because they do not allow the endogenous uh uh dopamine or endogenous thrown into they prevent the full action of endogenous dopamine and endogenous am I clear okay now we come to some indications of the antipsychotic drugs of course at the top there must be which disease psychosis we have discussed so many side effects of antipsychotic drugs but we did not mention about the allergic reactions like other drugs antipsychotic drugs can also produce allergic reaction in our body they may produce allergic skin reactions or they may produce hypersensitivity reaction against liver and jaundice or they may produce hypersensitivity reaction against bone marrow a granulocytosis clozapine should come to your mind and these drugs can also produce an unusual type of problem the most of the typical antipsychotic drugs reduce the threshold for Caesar they reduce the threshold for Caesar it means an patients who are epileptic patients we have to be careful in using typical antipsychotic drugs because chances of precipitation of epileptic attack are more is that right now I think we have a break and then we'll continue now few words about the pharmacokinetics of these drugs most of these drugs are taken orally it means they have to be absorbed from git but you must be knowing that any drug which is absorbed from the Git it has to pass through the liver isn't it and in the liver naturally through the portal circulation will break down into sinusoidal flow and then through hepatic veins it will go out into systemic yes circulation and from there to the systemic vein that will eventually drug will go to the right heart and passing through the yes through the lungs drug will eventually come to the left heart and then it will go to the all body is that right this is systemic circuit now listen carefully actually this is a basic rule all the drugs which work in the central of a system they must be highly lipid soluble the basic rule is all the drugs which work in the on the central level system must be highly lipid soluble because they must have a capacity to Cross Blood wind barrier they must have a capacity to cross the blood print barrier now any drug which is highly lipid soluble right that will not only cross a blood burn barrier that will also absorb easily from git and that any drug which can Cross Blood brain barrier will always cross a placental barrier is that right because absorption for grd mucosa it requires the junction dissolvement to lipids membranes of the cells from the systemic circulation going to the central of the system requires the structured pass through the bloodborne barrier and for if a female is pregnant if drug has to pass from Eternal circulation to the baby then it must have it need to cross the placental there so the drugs which are highly lipid soluble they have something common that they are absorbed from git very well now all those drugs like antipsychotic drugs they work on the central nervous system so they must be highly lipid soluble because these drugs are highly lipid soluble so whenever they are taken orally they are effectively absorbed but when they are passing through the portal circulation and they're passing through the liver because these drugs are highly lipid soluble they go into hepatocytes while they are passing through the liver they dissolve into a pathosite membrane and they load the hepatocyte and in the hepatocytes there's lot of endoplasmic reticulum more a drug is lipid soluble more drug will get dissolved into endoplasmic reticulum of hepatocyte and this is the hepatic endoplasmic reticulum which is very rich in drug metabolizing enzymes right these are what drug metabolizing enzymes drug metabolizing enzymes of proteins are floating in the lipids of endoplasmic reticulum in the hepatocyte so more a drug is lipid soluble more effective it will absorb from the jit more it will be trapped into hepatocytes more it will be dissolved into endoplasmic reticulum more chances it will be catabolized before it goes to the systemic circulation and the amount of drug which is catabolized when amount of drug which is catabolized before it reaches to systemic circulation that amount of drug is called the amount of drug undergoing first pass effect what is first pass fact whenever we take a drug orally if this drug some part of the drug is destroyed in the git or in Portal circulation or part of a drug is destroyed in the liver anywhere drug is destroyed in JT or in Portal circulation or in the liver right if drug is being destroyed as small then a smaller percentage reaches systemic circulation so we say if I say there's a drug which has 70 percent first pass effect it means out of 100 molecules which are absorbed only 30 will reach to the systemic circulation if I say drug has no first pass event it means uh whatever amount of drug is absorbed all of it is bio to the systemic circulation without any significant catabolism now as I told you the drugs we checked on the central nervous system as a principle they must be highly lipid soluble so all of them can be taken orally is the basic principle but all of them have a tendency to undergo first pass Metabolic Effect especially you look at the diazy pumps benzodiazepines you talk about barbiturate as you talk about anti-epileptic drugs or you talk about as a group antipsychotic drugs all these drugs have significant first possible so it's not just memorizing the drugs just remember one thing drug which is taken orally and for action ending compared to CNS must be highly lipid soluble so two things are evident immediately they have a chance they have a chance that they will be highly lipid they will be highly undergoing first pass effect ively they have a high chance to pass through what pass through the central barrier also so they may produce toxicity to the baby is that right now another important thing all the drugs which are highly liquid soluble if they go to systemic circulation how they will be carried they must be strongly bound with plasma proteins because leopard-soluble drug if they don't bind with the plasma protein they cannot be kept into blood into proper solution form and ah transported is that right so by its simple discussion I say antipsychotic drugs are acting in central nervous system do you think you need to memorize this thing there's no fun in memorize everyone understands psychosis must be something wrong with the central nervous system antipsychotic drugs must be going to central nervous system so it's easy to understand they must be overly absorbable drug they must be passing through high there must be strongly bound binding with plasma protein of course they must be capable of Crossing Blood band barrier and of course they must be able to cross placental barrier and of course to get these drugs out of the body we have to convert these highly lipid soluble dragon to water soluble drug it means we have to convert these lipid soluble Dragon to metabolites which are more polar metabolite so it means all of these drugs to get out of the body they have to undergo biotransformation reactions in the liver biotransformation reaction are defined as the reactions in the liver which alter the drug is that right so many of these drugs which are antipsychotic drugs in the liver they are converted into more polar metabolites and those more more polar water soluble metabolites are easily eliminated by the Reynolds in the urine or they are easily eliminated by the fecal matter am I clear is it difficult or easy to understand all this basic principle clear now we come to the uses of antipsychotic drugs of course at the top must be schizo frenia which is a very typical type of unfortunate situation right so uses are schizophrenia then second group of uses are schizoaffective disorders Okay so effective effective disorder mean mood disorders so effective disorders mean psychiatric disorders in which this pathology of the disease is mixture of schizophrenia and mood disorders either effective disorders right patient who has schizophrenia with mood disorders are it can be used in patients with psychosis due to psychosis which may be due to drugs or psychosis which is due to toxins or these drugs can be used in antipsychotic drugs right so we call it simply toxic psychosis in those conditions these drugs can be used then these drugs can be used in psychotic States psychotic States associated with severe depression or severe Mania you know in severe Mania and severe depression patient loses the contact with reality and patient may develop some degree of psychosis then antipsychotic drugs can be used then antipsychotic drugs can be used in Tourette's syndrome Tourette's syndrome Tourette Syndrome I told you this may be inherited familial disorder in which cauded nucleus neurotransformation is Disturbed and children may develop motor techs with vocal text motor Ticks Plus vocal Text Plus obscene gestures and obscene language then these drugs can be used in intractable hiccup as a symptomatic treatment intractable hiccup right especially chlorpromazine can be used for that purpose and again into Tourette Syndrome we use melendon molend on or another drug which can be used in Tourettes Syndrome is Fimo Primo site p i m o z i d parmeside then sometimes a special drug in this group is used for intractable pruritus itching intractable providers the drug which is used for this purpose is promethazone Pro methazone then these drugs can be used in MSS Ms has been vomiting sphere vomiting some of these drugs are anti-immatic also uh especially Prochlorperazine through Allure Para Zen right they can be used in a message as anti-matic agent then there is a special type of anesthesia which is called neuroleptic anesthesia neuro leptic anesthesia I will discuss about that anesthesia in detail when I teach you an aesthetic agents but in neuroleptic anesthesia we use dro peridol the drug is Dro dro periodol Plus the droparidol we use fentanyl what is fentanyl Fentanyl nyr no that is phenotion and theorismic Fentanyl is uh I think opioid drug short acting opiate opioid drug highly lipid soluble right so we call it neuroleptic dollar fentanyl so these are the basic uses of antipsychotic drugs and thank God this topic finishes thank you