1 00:00:00,000 --> 00:00:01,280 Speaker 1: All right, so we're going to be doing a farm 2 00:00:01,280 --> 00:00:04,080 review for our antipsychotic medications. Thank you so much for 3 00:00:04,120 --> 00:00:05,919 the support of the channel. Let's go ahead and get 4 00:00:05,919 --> 00:00:07,679 started with the basics. So we're going to be going 5 00:00:07,719 --> 00:00:11,320 over our first gens aka are typical antipsychotics, and our 6 00:00:11,400 --> 00:00:14,080 second gens known as atypicals. If you ever forget which 7 00:00:14,119 --> 00:00:16,600 generation is typical and which is atypical, you hold two 8 00:00:16,640 --> 00:00:19,000 fingers up for your second generation meds. Turn those two 9 00:00:19,039 --> 00:00:22,000 fingers upside down and it turns into an A four atypicals. Now, 10 00:00:22,000 --> 00:00:24,960 when we're talking about our antipsychotics and the conditions they treat, 11 00:00:25,000 --> 00:00:28,199 most notably schizophrenia, the leading theory, although still an active 12 00:00:28,199 --> 00:00:31,120 area of research, is that dopamine plays a central role. 13 00:00:31,399 --> 00:00:34,799 This regulation of dopamine signaling is thought to contribute to disease, 14 00:00:34,880 --> 00:00:39,039 and many antipsychotics exert their therapeutic effects by altering dopamine 15 00:00:39,079 --> 00:00:41,399 signaling in the brain. So to understand these mets, we've 16 00:00:41,399 --> 00:00:43,200 got to learn a little bit more about our friend 17 00:00:43,200 --> 00:00:46,799 dopamine and four specific dopamine pathways in the brain. Let's 18 00:00:46,840 --> 00:00:48,880 first talk about what they're supposed to do, which will 19 00:00:48,880 --> 00:00:51,520 help us understand what happens when things go wrong, as 20 00:00:51,560 --> 00:00:54,039 well as where our meds exert their therapeutic effect. So 21 00:00:54,119 --> 00:00:58,640 for dopamine pathways, you need to know mesolimbic, mesocritical, nigrostria, 22 00:00:59,000 --> 00:01:02,399 and tubero infintit. Let's first start with the mesolymbic pathway. 23 00:01:02,799 --> 00:01:06,000 So the mesolimbic dopamine pathway is a little pathway between 24 00:01:06,040 --> 00:01:09,400 the ventral tegmenttal area and the nucleus eccumbents of the brain. 25 00:01:09,680 --> 00:01:13,120 This is our reward center, so things like motivation, desire, pleasure. 26 00:01:13,319 --> 00:01:17,079 It's actually the primary area cocaine targets. So something feels good, 27 00:01:17,120 --> 00:01:19,040 this area of your brain motivates you to do it again. 28 00:01:19,200 --> 00:01:21,280 For example, purposes, I like to remember one word to 29 00:01:21,280 --> 00:01:24,359 associate which each of these, which helps remember key components. 30 00:01:24,359 --> 00:01:26,879 For mesolimbic, it's going to be motivation, and it's also 31 00:01:26,879 --> 00:01:29,319 important to know that excess dopamine here is thought to 32 00:01:29,359 --> 00:01:32,799 contribute to the positive symptoms we see in schizophrenium, like 33 00:01:32,840 --> 00:01:35,519 hallucinations and delusions. The next area we're going to be 34 00:01:35,519 --> 00:01:39,280 talking about is our mesocortical pathway. This connects the VTA 35 00:01:39,359 --> 00:01:43,680 to the pre frontal cortex. Dopamine here regulates emotions, cognition, 36 00:01:43,840 --> 00:01:46,840 executive function, et cetera. The one word association here is 37 00:01:46,920 --> 00:01:49,719 mood and schizophrenia. Dopamine here is thought to be low 38 00:01:49,840 --> 00:01:53,760 or hypo functioning, contributing to our negative symptoms flat affect, 39 00:01:54,000 --> 00:01:58,000 emotional withdrawal, and edonia aka inability to feel pleasure. The 40 00:01:58,040 --> 00:02:01,079 next two pathways, understanding their normal function is key because 41 00:02:01,079 --> 00:02:03,480 it's going to help us understand many of the adverse 42 00:02:03,719 --> 00:02:07,159 effects associated with the medications that will discuss shortly. So first, 43 00:02:07,200 --> 00:02:10,879 starting with the nigrostriadl which originates in the substantia niagra. 44 00:02:11,159 --> 00:02:13,879 Dopamine in this pathway plays an important role in movement 45 00:02:13,919 --> 00:02:16,319 and coordination. You can probably see where this is going. 46 00:02:16,360 --> 00:02:19,639 If dopamine promotes movement in this pathway, what might happen 47 00:02:19,680 --> 00:02:22,639 when an antipsychotic blocks too much dopamine here we'll talk 48 00:02:22,719 --> 00:02:24,639 more about that in just a moment. The one key 49 00:02:24,639 --> 00:02:27,400 to remember for the negrostrital pathway is going to be movement. 50 00:02:27,479 --> 00:02:30,960 And then finally, we have the tubero infandibular pathways, which 51 00:02:31,000 --> 00:02:34,439 connects the hypothalamus to the pituitary gland. Dopamine in this 52 00:02:34,479 --> 00:02:37,960 pathway inhibits the release of prolactin, and prolactin, as we know, 53 00:02:38,039 --> 00:02:41,639 promotes lactation among other things. Again, think about what might 54 00:02:41,680 --> 00:02:44,879 happen here if we block dopamine with our antipsychotics, and 55 00:02:44,919 --> 00:02:47,199 more about that soon. So your one word association for 56 00:02:47,280 --> 00:02:50,599 tubero infindibular is going to be milk, and that's your 57 00:02:50,599 --> 00:02:55,560 dopamine pathways mesolympic equals motivation, mesocortical mood, negrostrital movement, and 58 00:02:55,560 --> 00:02:58,560 tubero infandibular milk. Now that we have our framework, let's 59 00:02:58,599 --> 00:03:01,639 talk about our meds. Starting with are typical or first 60 00:03:01,639 --> 00:03:05,560 generation antipsychotics. So these are the ogs first developed in 61 00:03:05,560 --> 00:03:09,159 the nineteen fifties, with the first antipsychotic drug being chloropromazine. 62 00:03:09,240 --> 00:03:12,479 Interestingly enough, we still use chloropomazine today, but not so 63 00:03:12,560 --> 00:03:16,080 much for its antipsychotic properties, but actually for severe hiccups. 64 00:03:16,159 --> 00:03:18,879 It's true, so the use the first gens has declined 65 00:03:18,919 --> 00:03:21,800 over the years, not due to lack of efficacy, but 66 00:03:21,919 --> 00:03:24,199 due to their poor side effect profile compared to the 67 00:03:24,319 --> 00:03:27,800 newer second generation antipsychotics. Still got to know them, though, 68 00:03:27,840 --> 00:03:30,719 So this class includes a number of different medications which 69 00:03:30,759 --> 00:03:34,280 are classified by how potently they block D two receptors. 70 00:03:34,360 --> 00:03:38,080 Our high potency meds being halo paradol, flu fhenazine, loxipine, 71 00:03:38,080 --> 00:03:42,840 pure fenazine, pimozide, thiothyxine, and triflu parizine. And then we 72 00:03:42,879 --> 00:03:44,919 have our low potency meds, which are going to be 73 00:03:45,000 --> 00:03:48,439 thioritizine and chlorpromazine. There's a whole lot of meds here, 74 00:03:48,439 --> 00:03:50,680 and if you just want to remember one by all means, 75 00:03:50,759 --> 00:03:52,960 let it be haliparadol. This is what will likely be 76 00:03:53,039 --> 00:03:55,280 tested on as it's one of the most commonly used 77 00:03:55,319 --> 00:03:57,479 first gens. If you want to remember most of them, 78 00:03:57,520 --> 00:04:00,520 remember Halo paradal and your azines. The azenes suffix is 79 00:04:00,520 --> 00:04:04,479 seen in a majority of the first gen antipsychotics chloroprome, azine, 80 00:04:04,520 --> 00:04:07,199 flu fen azene, etc. I used to have this visual 81 00:04:07,240 --> 00:04:09,840 of the first edition of Halo magazine like Halo the 82 00:04:09,919 --> 00:04:11,520 video game, because I'm a nerd and I used to 83 00:04:11,520 --> 00:04:13,879 play a lot Halo when I was younger. So Halo 84 00:04:13,919 --> 00:04:17,120 help helps you remember, Halo Paradol magazine helps you remember 85 00:04:17,160 --> 00:04:19,800 your azine meds, and first edition helps you remember that 86 00:04:19,839 --> 00:04:22,439 these are your first gen antipsychotics. So those are your meds. 87 00:04:22,519 --> 00:04:26,040 Let's talk about the mechanism of action next. Now, all antipsychotics, 88 00:04:26,040 --> 00:04:28,160 whether it's first or second gen, are going to mess 89 00:04:28,199 --> 00:04:30,839 with dopamine in one way or another, depending on the 90 00:04:30,839 --> 00:04:34,240 med different strength of dopamine manipulation, and varying methods. But 91 00:04:34,319 --> 00:04:36,800 in the case of first gen, the primary mechanism is 92 00:04:36,839 --> 00:04:40,040 through inhibition of D two dopamine receptors in the brain. 93 00:04:40,319 --> 00:04:43,079 The therapeutic effect of these drugs is by post synaptic 94 00:04:43,120 --> 00:04:46,079 blockade of dopamine D two receptors in the brain. So 95 00:04:46,160 --> 00:04:49,439 blocking dopamine receptors, how does that help a patient with schizophrenia, 96 00:04:49,519 --> 00:04:51,920 for instance? And to answer that, we need to revisit 97 00:04:51,959 --> 00:04:56,240 the dopamine pathways we discussed earlier, specifically the mesolimbic pathway 98 00:04:56,360 --> 00:04:59,439 our motivation center, where excess dopamine here is thought to 99 00:04:59,480 --> 00:05:02,759 contribute to the positive symptoms of schizophrenia, as we went 100 00:05:02,800 --> 00:05:05,600 over hallucinations and delusions, et cetera. So if we block 101 00:05:05,639 --> 00:05:09,120 dopamine receptors in this pathway with a first gen theoretically 102 00:05:09,199 --> 00:05:12,240 we can reduce the symptoms. And there is a therapeutic 103 00:05:12,279 --> 00:05:15,040 window for the number of D two receptors blocked, typically 104 00:05:15,079 --> 00:05:18,480 around sixty five to seventy percent. D two blockade is 105 00:05:18,519 --> 00:05:21,759 the sweet spot. You block less, decrease efficacy. You block more, 106 00:05:21,800 --> 00:05:25,000 you have more adverse effects. Now, what about the mesocortical pathway. 107 00:05:25,000 --> 00:05:28,160 Remember mesocortical equals mood, where dopamine is already thought to 108 00:05:28,160 --> 00:05:31,759 be low in schizophrenia, causing our negative symptoms. And since 109 00:05:31,839 --> 00:05:35,439 first gens further block dopamine in this pathway, it's thought 110 00:05:35,920 --> 00:05:39,160 that they have little effect on negative symptoms and potentially 111 00:05:39,360 --> 00:05:43,000 potentially may worsen them in some patients, although evidence for 112 00:05:43,040 --> 00:05:45,199 this remains limited and a lot of this is still 113 00:05:45,240 --> 00:05:48,240 being researched. So for the exam, focus on first generation 114 00:05:48,279 --> 00:05:52,079 antipsychotics blocking D two receptors in the brain, reducing positive 115 00:05:52,079 --> 00:05:54,519 symptoms for your mechanism of action, let's move on to 116 00:05:54,560 --> 00:05:58,399 indications for these meds. Of course, schizophrenia and schizoeffective disorders, 117 00:05:58,439 --> 00:06:01,480 acute mania a severe episodes of bipolar mania that is 118 00:06:01,560 --> 00:06:06,000 usually combined with lithium, major depressive disorder with psychotic features 119 00:06:06,160 --> 00:06:09,360 and severe agitation, plus a number of other conditions, and 120 00:06:09,480 --> 00:06:13,439 like we discussed before, first generation antipsychotics can treat these conditions, 121 00:06:13,439 --> 00:06:16,279 but they have largely been replaced by second generation or 122 00:06:16,360 --> 00:06:20,439 atypical antipsychotics, particularly in the treatment of schizophrenia due to 123 00:06:20,439 --> 00:06:23,759 their higher risk of movement or extra perimidal side effects, 124 00:06:23,879 --> 00:06:25,879 So I wouldn't focus too much on the indications as 125 00:06:25,879 --> 00:06:28,319 you won't use these that often, except in the case 126 00:06:28,360 --> 00:06:31,079 of severe agitation and the impatient or emergency setting where 127 00:06:31,079 --> 00:06:34,120 they're still pretty commonly used. This will usually be with 128 00:06:34,199 --> 00:06:37,040 a rapid acting first gen like helo paradol combined with 129 00:06:37,040 --> 00:06:39,639 the benzo. All Right, the next part is the most important, 130 00:06:39,639 --> 00:06:42,839 and that's the adverse effects. There are many adverse effects 131 00:06:42,839 --> 00:06:46,000 associated with antipsychotics, and I could easily spend an entire 132 00:06:46,040 --> 00:06:48,000 lesson covering all of them, but for this review, we're 133 00:06:48,040 --> 00:06:50,879 going to focus on the high fieled effects for your exams, 134 00:06:51,000 --> 00:06:54,000 especially those that are more commonly associated with your first 135 00:06:54,040 --> 00:06:56,759 gen antipsychotics. So for adverse effects, I want you to 136 00:06:56,759 --> 00:07:01,600 remember to dread neuroliptic malignant syndrome ED neualiptic malignant syndrome. 137 00:07:01,680 --> 00:07:04,000 You'll know the highest yield adverse effects for your first 138 00:07:04,000 --> 00:07:07,079 gens and also know to dread and or elliptic malignant syndrome, 139 00:07:07,079 --> 00:07:09,480 which is the most feared adverse effect of this class, 140 00:07:09,480 --> 00:07:11,839 as it can be fatal. So let's start with the 141 00:07:12,000 --> 00:07:14,560 dread portion of the mnemonic, which helps us remember our 142 00:07:14,720 --> 00:07:18,199 extra perameteral side effects. These are our movement disorders, which 143 00:07:18,240 --> 00:07:20,839 are more common in first gens. Let's first start with 144 00:07:20,920 --> 00:07:23,680 why this happens. Then we'll talk about which specific movement 145 00:07:23,680 --> 00:07:25,839 disorders to know for the exam. So let's go back 146 00:07:25,879 --> 00:07:28,720 again to the dopamine pathways. Which pathway do you think 147 00:07:28,759 --> 00:07:31,839 contributes to our movement disorders with these mets. That's right, 148 00:07:31,920 --> 00:07:36,079 the negrostrital pathway, the dopamine highway that control movement and coordination. 149 00:07:36,439 --> 00:07:39,199 So if this movement pathway is fueled by dopamine, what 150 00:07:39,240 --> 00:07:41,000 do you think will happen when we throw a first 151 00:07:41,000 --> 00:07:44,040 gen in there, which we know blocks dopamine. Not surprisingly, 152 00:07:44,279 --> 00:07:47,839 movement disorders develop. In fact, blocking dopamine in the negrostrital 153 00:07:47,879 --> 00:07:51,399 pathway creates a situation similar to Parkinson's disease, which is 154 00:07:51,399 --> 00:07:56,680 why antipsychotic induced movement disorders closely resemble Parkinsonian symptoms. So 155 00:07:56,720 --> 00:07:59,560 now let's talk about these specific extra perametal symptoms you 156 00:07:59,560 --> 00:08:03,000 need to know ZH using the dreadnomonic dr EA D 157 00:08:03,560 --> 00:08:06,879 starting with D which stands for dystonia, Acute dystonia is 158 00:08:06,879 --> 00:08:09,639 one of the earliest adverse effects, peaking at around twenty 159 00:08:09,639 --> 00:08:12,120 four to forty eight hours from the initiation of therapy, 160 00:08:12,600 --> 00:08:18,319 and it involves involuntary muscle contractions or spasms of the face, neck, eyes, back, 161 00:08:18,399 --> 00:08:22,480 and muscle stiffness and contractions, which can actually be quite painful. Next, 162 00:08:22,519 --> 00:08:25,040 the R is going to stand for rigidity, so rigidity 163 00:08:25,079 --> 00:08:28,079 of the limbs resistant to passive movement, which is one 164 00:08:28,120 --> 00:08:31,399 of the most obvious features of drug induced parkinsonism we 165 00:08:31,439 --> 00:08:33,480 can see in these patients. It may present as lead 166 00:08:33,519 --> 00:08:37,919 pipe or codwheal rigidity. Next, the E stands for I deviation. Now, 167 00:08:37,919 --> 00:08:40,559 this is related to the acute dystonia and is formally 168 00:08:40,600 --> 00:08:44,679 called oculogyric crisis where there is this spasmodic deviation of 169 00:08:44,679 --> 00:08:47,279 the extra ocular muscles causing the eyes to look upward. 170 00:08:47,600 --> 00:08:49,480 Not super high yield, but just be aware of it. 171 00:08:49,600 --> 00:08:52,879 Next to the A stands for Acathesia is uncontrollable inner 172 00:08:52,919 --> 00:08:57,000 restlessness and compelling urge to move the body tapping, rocking 173 00:08:57,039 --> 00:08:58,759 back and forth, and it can be one of the 174 00:08:58,759 --> 00:09:01,440 most distressing side effects of these drugs. So I do 175 00:09:01,480 --> 00:09:03,720 not intend to make light of this with my sillynomodic. 176 00:09:03,960 --> 00:09:07,120 This is just how I remembered it. Acathesia. I used 177 00:09:07,120 --> 00:09:10,480 to think of a cat in acathesia, a restless cat 178 00:09:10,519 --> 00:09:14,200 that can't sit still, constantly pacing, scratching, and tapping its 179 00:09:14,240 --> 00:09:16,919 paws like most cats do to help remember the compelling 180 00:09:17,039 --> 00:09:20,440 urge to move the body, tapping, etc. Seen in acat theesia. 181 00:09:21,039 --> 00:09:24,799 And finally, the D stands for dyskinesia, as in tardive diskanesia. 182 00:09:24,840 --> 00:09:28,519 Tardiv diskanesia is a late manifestation, usually occurring after months 183 00:09:28,559 --> 00:09:31,360 of being on the medication. The word tardive actually is 184 00:09:31,399 --> 00:09:34,279 derived from the Latin term tartis, meaning late or tardi, 185 00:09:34,320 --> 00:09:36,879 which makes sense as this is a late manifestation occurring 186 00:09:36,919 --> 00:09:39,639 after many months. So while the arms, legs, and trunk 187 00:09:39,639 --> 00:09:43,279 can be affected with this condition, tardev diskeanesia mainly targets 188 00:09:43,320 --> 00:09:46,600 the tongue and mouth, leading to these unique manifestations with 189 00:09:46,759 --> 00:09:49,720 twisting of the tongue, chewing, grimacing movements of the face. 190 00:09:50,039 --> 00:09:52,360 The word tar and tardive diskeanesia would always make me 191 00:09:52,399 --> 00:09:54,159 think of what your face would look like if you 192 00:09:54,200 --> 00:09:57,120 were chewing a piece of sticky, chewy tar all right, 193 00:09:57,120 --> 00:09:59,600 So those are your extra pyramidal symptoms, very high yield 194 00:09:59,679 --> 00:10:05,840 for our again, remember dread dystonia, rigidity, I deviation, acathesia, dyskinesia. Next, 195 00:10:05,919 --> 00:10:09,360 let's talk about neualeptic malignant syndrome or NMS. Why do 196 00:10:09,440 --> 00:10:12,039 we dread NMS with our first gens. Well, that's because 197 00:10:12,039 --> 00:10:15,399 this complication well rare can be fatal. NMS is a 198 00:10:15,519 --> 00:10:18,720 neurologic emergency associated most commonly with the use of first 199 00:10:18,720 --> 00:10:21,840 generation antipsychotics, and that's why you dread NMS with the 200 00:10:21,879 --> 00:10:26,200 first gens. Manifestations of NMS are fever, muscle rigidity, autonomic 201 00:10:26,240 --> 00:10:30,799 instability usually accompanied by rabdough and creating kinase elevation. Treatment 202 00:10:30,840 --> 00:10:32,879 is fairly high yield and easy to remember as you 203 00:10:32,919 --> 00:10:36,200 treat with the four DS. The four DS are discontinuation 204 00:10:36,360 --> 00:10:39,240 of the offending agent. In this case, we would be antipsychotics. 205 00:10:39,320 --> 00:10:42,399 XD is for dantriline, a muscle relaxant. Next is your 206 00:10:42,480 --> 00:10:46,320 D two agonist like bromocryptine, and finally diazepam or other 207 00:10:46,320 --> 00:10:49,759 benzos to mitigate agitation. Now, there are of course a 208 00:10:49,840 --> 00:10:54,080 number of other adverse effects QT prolongation, prolactant elevation. Since 209 00:10:54,080 --> 00:10:57,440 they're non selective, they also may block histamine alpha one 210 00:10:57,480 --> 00:11:00,399 and muscarinic receptors, so there can be sedation, hypo tension, 211 00:11:00,480 --> 00:11:03,200 urinary retention. But for the exam, I'd stick to dread 212 00:11:03,279 --> 00:11:06,519 nms as that's the highest yield ADRs for this class. 213 00:11:06,600 --> 00:11:08,799 And that brings us to our second generation or our 214 00:11:08,879 --> 00:11:15,519 atypical antipsychotics. So first, why are they called atypical? What 215 00:11:15,639 --> 00:11:19,080 makes them atypical? Well, primarily because of the lower propensity 216 00:11:19,080 --> 00:11:21,679 to induce EPs or movement disorders like we just talked 217 00:11:21,720 --> 00:11:24,399 about with our first gens, and it also originally implied 218 00:11:24,399 --> 00:11:27,240 that these newer drugs were fundamentally different than first gens. 219 00:11:27,320 --> 00:11:30,440 But not all second generation antipsychotics behave the same way, 220 00:11:30,480 --> 00:11:32,960 so the naming system it's not perfect. But with that 221 00:11:33,000 --> 00:11:35,440 being said, let's first talk about what medications are included 222 00:11:35,440 --> 00:11:37,840 in this class. So the men's included in this class 223 00:11:37,840 --> 00:11:50,759 include erapiprasol a, centipine, brex pipersol, cariprazine, closetpine, eloparodone, lumteperone, luracidone, olanzipine, paloparidone, quetiapine, resparodone, 224 00:11:50,879 --> 00:11:54,279 and zeprasidone, Like, seriously, arery, Katie mee? Who's gonna remember 225 00:11:54,320 --> 00:11:57,200 all of that? So here's the good news. From exam standpoint, 226 00:11:57,279 --> 00:11:59,759 there's really only four to focus on. The four that 227 00:11:59,799 --> 00:12:02,000 are always test it on due to their adverse effects 228 00:12:02,039 --> 00:12:06,200 are closipine, resparidone, lanzipene, and quotipine, So you need to 229 00:12:06,200 --> 00:12:10,000 know those closipine, resparadone, lanzipene, quotipine. I just remember the 230 00:12:10,039 --> 00:12:14,440 sentence crocs are atypical shoes. Crocs are atypical shoes. Crocs 231 00:12:14,480 --> 00:12:19,879 are spelled cr Q. The first letters of closipine, resparodone, lanzipine, 232 00:12:19,919 --> 00:12:23,320 and quotiapine are atypical shoes. Atypical helps you remember that 233 00:12:23,360 --> 00:12:27,320 these are atypical antipsychotics and no offense to anyone wearing crocs, 234 00:12:27,320 --> 00:12:31,559 but they kind of are atypical shoes. So again, closeipine, resparodone, olanzipene, 235 00:12:31,600 --> 00:12:35,480 quotiapine aka crocs are atypical shoes. Next, let's talk about 236 00:12:35,480 --> 00:12:38,120 how these meds work, which is by inhibiting D two 237 00:12:38,200 --> 00:12:43,200 dopamine receptors plus serotonin five HT two A receptors. Now, 238 00:12:43,200 --> 00:12:44,919 before we dive deeper, I want to point out that 239 00:12:44,960 --> 00:12:48,480 second generation antipsychotics are a diverse group of meds, and 240 00:12:48,559 --> 00:12:51,320 not all of them follow this exact mechanism. For example, 241 00:12:51,440 --> 00:12:55,360 era pippersol, brex pippersol, and cariprazine are sometimes referred to 242 00:12:55,399 --> 00:12:59,200 as third gen antipsychotics by some sources because they act 243 00:12:59,200 --> 00:13:02,840 as partial dopamine agonists rather than pure dopamine blockers. But 244 00:13:02,879 --> 00:13:04,960 with that being said, the general mechanism you should focus 245 00:13:05,039 --> 00:13:07,159 on for your exam for most of these meds is 246 00:13:07,159 --> 00:13:11,960 that second generation antipsychotics affect both dopamine and serotonin signaling. So, 247 00:13:12,039 --> 00:13:15,200 like first gen antipsychotics, they block post synaptic dopamine D 248 00:13:15,240 --> 00:13:17,879 two receptors. But what really sets them apart as their 249 00:13:17,879 --> 00:13:22,679 additional blockade of serotonin receptors, particularly the five HT two 250 00:13:22,720 --> 00:13:25,480 A receptor. In many of these meds, the serotonin blocking 251 00:13:25,519 --> 00:13:29,639 effects are relatively greater than their dopamine blocking effects. Additionally, 252 00:13:29,639 --> 00:13:33,240 some second gen agents will exhibit lower D two receptor 253 00:13:33,240 --> 00:13:37,679 occupancy or more transient binding to these dopamine receptors, a 254 00:13:37,720 --> 00:13:42,080 distinction that will become important when we discuss adverse effects later. Now. Initially, 255 00:13:42,120 --> 00:13:44,759 it was thought that this additional serotonin blockade made them 256 00:13:44,759 --> 00:13:48,320 more effective for treating negative symptoms of schizophrenia, but the 257 00:13:48,360 --> 00:13:51,240 evidence really has been mixed and many studies have found 258 00:13:51,279 --> 00:13:54,879 similar efficacy between first and second generation antipsychotics. So the 259 00:13:54,960 --> 00:13:57,720 key distinction to remember for the exam first gens primarily 260 00:13:57,720 --> 00:14:01,360 block dopamine. Second gens generally effect both dopamine and serotonin. 261 00:14:01,559 --> 00:14:03,879 All right, indications, of course, we are going to have 262 00:14:04,320 --> 00:14:06,879 schizophrenia with our second gens, which are going to be 263 00:14:06,919 --> 00:14:09,960 preferred over the first gens for this condition due to 264 00:14:10,039 --> 00:14:13,879 the lower incidents of extra parameiteral symptoms ecthesia, dystonia, et cetera. 265 00:14:14,440 --> 00:14:18,360 Bipolar disorder is another one, and major depressive disorder as 266 00:14:18,360 --> 00:14:23,000 an adjunctive therapy. There are others korea and Huntington disease, 267 00:14:23,080 --> 00:14:26,600 postpartum psychosis, but focus on those three, with schizophrenia being 268 00:14:26,639 --> 00:14:28,639 at the top of that list. Next, let's talk about 269 00:14:28,639 --> 00:14:31,480 the adverse effects, which is probably the most commonly tested 270 00:14:31,480 --> 00:14:34,080 on component. So let's start with what we've already touched 271 00:14:34,080 --> 00:14:38,720 on previously. Second genss can cause extra parameteral symptoms, but 272 00:14:38,799 --> 00:14:41,440 less often compared to our first gens. So why do 273 00:14:41,519 --> 00:14:44,440 these movement disorders occur less often with second gens? Well 274 00:14:44,519 --> 00:14:47,799 back to the MOA. These drugs are still dopamine blockers, 275 00:14:47,840 --> 00:14:52,519 but they're also serotonin blockers, and comparatively, their serotonin receptor 276 00:14:52,519 --> 00:14:56,279 binding exceeds their dopamine receptor binding, which varies by the 277 00:14:56,279 --> 00:15:00,000 specific drug, but as a general principle, second generation antipsychotics 278 00:15:00,080 --> 00:15:03,120 bind more loosely to D two receptors compared to first 279 00:15:03,120 --> 00:15:06,399 generation agents. The theory is weaker D two binding allows 280 00:15:06,399 --> 00:15:09,200 more dopamine activity to be preserved in pathways like the 281 00:15:09,320 --> 00:15:13,200 nigrostriatal tract, which translates to a lower risk of movement disorders. 282 00:15:13,320 --> 00:15:15,799 So no that they still can cause them, but less often. 283 00:15:15,840 --> 00:15:18,679 Most importantly, next, let's talk about the other adverse effects, 284 00:15:18,679 --> 00:15:21,679 starting with the most important and prominent for your second GENS, 285 00:15:21,840 --> 00:15:25,200 which is going to be metabolic syndrome. You'll think weight gain, diabetes, 286 00:15:25,240 --> 00:15:28,279 dyslibidemia as a class. This is the most important adverse 287 00:15:28,279 --> 00:15:30,440 effect for you to know. For first gens, it was 288 00:15:30,480 --> 00:15:33,240 your extra paramidal. For second gens, it is metabolic syndrome. 289 00:15:33,320 --> 00:15:35,720 It's so prevalent with this class it's recommended to actually 290 00:15:35,799 --> 00:15:39,080 monitor weight, BP, fasting, glucose, and lipids when patients are 291 00:15:39,120 --> 00:15:41,840 started on these meds. Now, when we're talking about weight gain, 292 00:15:41,879 --> 00:15:44,039 even though all of the second gens can cause weight gain, 293 00:15:44,039 --> 00:15:46,320 there's one that you need to know that causes it 294 00:15:46,360 --> 00:15:49,279 the most, and that's going to be olanzipine. A Lenzopene 295 00:15:49,360 --> 00:15:52,919 is the second generation antipsychotic most commonly associated with significant 296 00:15:52,919 --> 00:15:56,799 weight gain and other metabolic complications. Clauspine causes a similar 297 00:15:56,840 --> 00:15:58,799 degree of weight gain, but it's got way other high 298 00:15:58,879 --> 00:16:01,720 yield associations will go for shortly, so for exams, think 299 00:16:01,720 --> 00:16:05,840 olanzapine equals obesity. Luckily, it's the only antipsychotic that starts 300 00:16:05,879 --> 00:16:08,080 with an O. The O in your mind should stand 301 00:16:08,080 --> 00:16:10,480 for obesity when you see this on your exam. Next 302 00:16:10,519 --> 00:16:13,919 is going to be hyper prolactinemia, oh, elevated prolactin levels. Now, 303 00:16:13,919 --> 00:16:17,039 this can of course happen with our first gens, like haloparadol, 304 00:16:17,279 --> 00:16:19,039 but I wanted a wait to speak about this until 305 00:16:19,039 --> 00:16:21,279 we got to our second gens because there's a second 306 00:16:21,320 --> 00:16:24,440 gen med notorious for this and therefore the one you 307 00:16:24,480 --> 00:16:26,480 need to know for your exam before we get to that. 308 00:16:26,600 --> 00:16:29,039 Why do we have prolactin elevation and development of things 309 00:16:29,080 --> 00:16:31,480 like lactaria in the first place. Back to the dopamine 310 00:16:31,519 --> 00:16:34,919 highway again, remember the tubera in finndibular track or dopamine 311 00:16:34,919 --> 00:16:38,480 travel to the pituitary to inhibit the secretion of prolactin. Well, 312 00:16:38,519 --> 00:16:41,759 when we blocked dopamine here with our antipsychotics, we remove 313 00:16:41,840 --> 00:16:45,559 prolactin inhibition and prolactin levels where therefore rise and patients 314 00:16:45,559 --> 00:16:49,240 can develop hyper prolactinemia with adverse effects like glactariea among 315 00:16:49,399 --> 00:16:51,600 other things as well. So the one drug you have 316 00:16:51,679 --> 00:16:54,679 to know that is notorious for this is resperidone. Now, 317 00:16:54,679 --> 00:16:56,480 we just went over the moa of second gens and 318 00:16:56,519 --> 00:16:58,559 I made a point to mention that second gens are 319 00:16:58,600 --> 00:17:02,039 generally weaker D two lockers. So why does resperidone, a 320 00:17:02,120 --> 00:17:06,160 second generation drug, cause hyperprolectinemia so frequently, which is a 321 00:17:06,200 --> 00:17:09,279 side effect driven by dopemine blockade. And the answer to 322 00:17:09,319 --> 00:17:12,640 that is Resparadone is somewhat of an outlier among the atypicals. 323 00:17:12,799 --> 00:17:15,279 Unlike many other drugs in this class, it functions more 324 00:17:15,359 --> 00:17:17,880 like a first gen in that it's a more potent 325 00:17:17,960 --> 00:17:20,640 D two blocker, and that's why we see dopemine block 326 00:17:20,920 --> 00:17:25,039 mediated adverse effects like hyperprolactinemia as well as more extra 327 00:17:25,079 --> 00:17:27,599 paramidal symptoms. So while there are other drugs that can 328 00:17:27,680 --> 00:17:30,960 cause hyperprolactinemia, do not forget resparadone as it's one of 329 00:17:31,000 --> 00:17:33,839 the most common to cause this and it's always tested 330 00:17:33,880 --> 00:17:36,160 on the way that you can remember resparadone is linked 331 00:17:36,200 --> 00:17:40,079 to hyperprolactinemia and galactorea is by instead of remembering resperidone, 332 00:17:40,160 --> 00:17:43,960 remember it as respey dairy. Not a very appropriatemnomonic and 333 00:17:44,000 --> 00:17:48,319 I apologize, but respeery dairy dairy dai r y instead 334 00:17:48,319 --> 00:17:51,880 of resperidone helps remember the galactorea aka milk discharge from 335 00:17:51,920 --> 00:17:55,519 the breast associated with this medication secondary to hyper prolectinemia. 336 00:17:55,640 --> 00:17:59,319 So again remember instead of resperidone, remember it as respery dairy. 337 00:17:59,640 --> 00:18:02,839 Next going to be QT prolongation. So your antipsychotics can 338 00:18:02,880 --> 00:18:06,079 cause QT prolongation, but there's two second gens that cause 339 00:18:06,119 --> 00:18:08,359 it the most, and these are going to be quotiopine 340 00:18:08,440 --> 00:18:11,480 and zeprasidone. And it's easy to remember that quotiapine causes 341 00:18:11,559 --> 00:18:14,440 QT prolongation because the Q is far from the T 342 00:18:14,880 --> 00:18:17,039 and quotiapine the Q is far from the t and 343 00:18:17,079 --> 00:18:21,400 the spelling of quotiopine q u E t ia pi 344 00:18:21,640 --> 00:18:25,000 n E, which helps remember. This medication, along with zeprasidone, 345 00:18:25,079 --> 00:18:27,680 have the highest risk of QT prolongation compared to the 346 00:18:27,680 --> 00:18:31,920 other meds in this class. Next, we have undone. A granulocytosis. 347 00:18:31,960 --> 00:18:34,559 This is a dangerous and potentially deadly drop in white 348 00:18:34,559 --> 00:18:37,680 blood cells, more specifically neutrophils. And when you hear a 349 00:18:37,799 --> 00:18:41,279 granulo psytosis on a psychic exam, closipine is the answer 350 00:18:41,359 --> 00:18:44,920 that you are looking for. Closipine is a second generation antipsychotic, 351 00:18:44,960 --> 00:18:47,440 but it's quite different than all of the other drugs 352 00:18:47,440 --> 00:18:51,279 in this class. It's actually way way more effective, arguably 353 00:18:51,319 --> 00:18:54,599 the most effective antipsychotic we have, especially in the treatment 354 00:18:54,640 --> 00:18:58,680 of resistant schizophreniam. So if it's so damn effective why 355 00:18:58,759 --> 00:19:03,319 isn't closipene first line for everybody with schizophrenia well a granulocytosis. 356 00:19:03,519 --> 00:19:06,000 This medication was initially tested in patients in Finland in 357 00:19:06,039 --> 00:19:09,519 the nineteen seventies. They found great efficacy, but people started 358 00:19:09,920 --> 00:19:13,720 dying secondary to a granulocytosis. So cloudspin is still used 359 00:19:13,759 --> 00:19:16,960 in treatment resistant schizophrenia, and it's actually first line for 360 00:19:17,000 --> 00:19:19,880 the specific indication, of course, after patients have tried many 361 00:19:19,920 --> 00:19:23,160 other meds in the class, but it requires frequent labs 362 00:19:23,160 --> 00:19:25,720 to assess the absolute neutrophil count as frequent as every 363 00:19:25,720 --> 00:19:28,640 week during the first six months and then less so thereafter, 364 00:19:28,839 --> 00:19:31,000 so you have to know this association with this medication. 365 00:19:31,079 --> 00:19:33,640 It is super high yield. So remember Closipine is a 366 00:19:33,640 --> 00:19:37,319 white cell fiend. Closepine is a white cell fiend. Claspine 367 00:19:37,359 --> 00:19:39,720 is I don't know, snatching up all of those white cells, 368 00:19:39,759 --> 00:19:42,319 all those neutrophils and maybe like eating them or something 369 00:19:42,519 --> 00:19:45,640 in the visual in your head. But closibine is a 370 00:19:45,640 --> 00:19:47,960 white cell fiend, which helps you remember these super high 371 00:19:48,000 --> 00:19:51,640 yield adverse effects of a granulocytosis associated with this medication. 372 00:19:51,720 --> 00:19:54,079 You cannot forget that, So those are your adverse effect 373 00:19:54,359 --> 00:19:56,319 for your second gens. There are, of course plenty of 374 00:19:56,319 --> 00:19:59,119 others neueleiptic malignant syndrome, although this is more common in 375 00:19:59,119 --> 00:20:03,039 first gen on it for that class, sedation, hypotension, urinary retention, 376 00:20:03,160 --> 00:20:07,160 thyroid abnormalities, among others. But the focus should be first 377 00:20:07,240 --> 00:20:10,519 and foremost on metabolic syndrome with weight gain, diabetes, et cetera. 378 00:20:10,640 --> 00:20:14,279 Remember the OH and Olanzipine stands for obesity, Rosperidone associated 379 00:20:14,319 --> 00:20:19,960 with hyperprolactinemia in galactoia aka risperidairy QT prolongation with zeprasidone 380 00:20:20,000 --> 00:20:22,039 in quotypine. Remember the key was far from the T 381 00:20:22,160 --> 00:20:26,240 in quotypine. A granliocytosis with closipine because closipine is a 382 00:20:26,240 --> 00:20:28,839 white cell fiene. And of course remember your extra perramidal 383 00:20:28,880 --> 00:20:31,440 symptoms happen but less frequent compared to first gens, and 384 00:20:31,480 --> 00:20:33,799 that is your antipsychotics. I hope that was helpful. Thank 385 00:20:33,839 --> 00:20:35,640 you so much for listening, and as always, best of 386 00:20:35,720 --> 00:20:36,359 luck in school