S1E59 Antipsychotic Drugs (Typical vs Atypical)

Scott Shapiro (0:00)

All right, so we're going to be doing a farm review for our antipsychotic medications. Thank you so much for the support of the channel. Let's go ahead and get started with the basics. So we're going to be going over our first gens, aka our typical antipsychotics, and our second gens, known as atypicals. If you ever forget which generation is typical and which is atypical, you hold two fingers up for your second generation meds, turn those two fingers upside down, and it turns into an A for atypicals. Now, when we're talking about our antipsychotics and the conditions they treat, most notably schizophrenia, the leading theory, although still an active area of research, is that dopamine plays a central role. Dysregulation of dopamine signaling is thought to contribute to disease and many antipsychotics exert their therapeutic effects by altering dopamine signaling in the brain. So to understand these meds, we got to learn a little bit more about our friend dopamine and four specific dopamine pathways in the brain. Let's first talk about what they're supposed to do, which will help us understand what happens when things go wrong, as well as where our meds exert their therapeutic effect. So for dopamine pathways, you need to know mesolimbic, mesocortical, nigrostriatal, and tubroinfandibular. Let's first start with the mesolimbic pathway.

So the mesolimbic dopamine pathway is a little pathway between the ventral tegmental area and the nucleus accumbens of the brain. This is our reward center. So things like motivation, desire, pleasure, it's actually the primary area, cocaine targets. So if something feels good, this area of your brain motivates you to do it again. For exam purposes, I like to remember one word to associate with each of these, which helps to remember key components. For mesolimbic, it's going to be motivation. And it's also important to know that excess dopamine here is thought to contribute to the positive symptoms we see in schizophrenia, like hallucinations and delusions. The next area we're going to be talking about is our mesocortical pathway. This connects the VTA to the prefrontal cortex. Dopamine here regulates emotions, cognition, executive function, etc. The one word association here is mood. In schizophrenia, dopamine here is thought to be low or hypo-functioning contributing to our negative symptoms, flat affect, emotional withdrawal, anhedonia, aka inability to feel pleasure.

The next two pathways, understanding their normal function is key because it's going to help us understand many of the adverse effects associated with the medications that we'll discuss shortly. So first, starting with the nigrostriatal, which originates in the substantia nigra. Dopamine in this pathway plays an important role in movement and coordination. You can probably see where this is going. If dopamine promotes movement in this pathway, what might happen when an antipsychotic blocks too much dopamine here? We'll talk more about that in just a moment. The one key to remember for the nigrostriatal pathway is going to be movement. And then finally, we have the tuberoinfundibular pathways, which connects the hypothalamus to the pituitary gland. Dopamine in this pathway inhibits the release of prolactin, and prolactin, as we know, promotes lactation, among other things. Again, think about what might happen here if we block dopamine with our antipsychotics, and more about that soon. So your one word association for tuberoinfundibular is going to be milk, and that's your dopamine pathways. Mesolimbic equals motivation, mesocortical mood, nigrostriatal movement, and tuberoinfundibular milk. Now that we have our framework, let's talk about our meds, starting with our typical or first-generation antipsychotics. So these are the OGs, first developed in the 1950s, with the first antipsychotic drug being chlorpromazine. Interestingly enough, we still use chlorpromazine today, but not so much for its antipsychotic properties, but actually for severe hiccups. It's true.

So the use of the first-gens has declined over the years, not due to lack of efficacy, but due to their poor side-effect profile compared to the newer second-generation antipsychotics. Still gotta know them though, so this class includes a number of different medications, which are classified by how potently they block D2 receptors. Our high-potency meds being haloperidol, flufenazine, loxapine, perphenazine, pimoside, thiothixine, and trifluperozine. And then we have our low-potency meds, which are going to be thyridazine and chlorpromazine. There's a whole lot of meds here, and if you just want to remember one by all means, they're going to be haloperidol. This is what will likely be tested on, as it's one of the most commonly used first-gens. If you want to remember most of them, remember haloperidol and your azines. The azine suffix is seen in a majority of the first-gen anti-psychotics, chlorpromazine, flufenazine, et cetera. I used to have this visual of the first edition of Halo magazine, like Halo the video game, because I'm a nerd, and I used to play a lot of Halo when I was younger.