Typical antipsychotics

Definitions & Key takeaways

Typical antipsychotics, also known as first-generation antipsychotics, are a class of medications used to treat various psychiatric disorders, particularly schizophrenia and other psychotic disorders. They work by blocking dopamine D2 receptors in the mesolimbic pathway in the brain, which helps to reduce the symptoms of psychosis.

Typical antipsychotics include medications such as chlorpromazine, haloperidol, and fluphenazine. These medications are generally effective at reducing positive symptoms of psychosis, such as hallucinations and delusions, but may have limited effectiveness for negative symptoms and may also cause significant side effects.

Common side effects of typical antipsychotics include extrapyramidal symptoms, such as tremors and muscle rigidity, as well as weight gain, sedation, and sexual dysfunction. Long-term use of these medications may also be associated with a higher risk of developing tardive dyskinesia, a movement disorder characterized by involuntary muscle movements.

Chapters:

Watch video only

Introduction0:00–0:32

Antipsychotics, as their name implies, are mainly used to treat schizophrenia and other psychotic conditions. Even though the exact cause of schizophrenia is still unknown, there's some evidence that suggests it’s related to altered levels of the neurotransmitter dopamine.
Now, antipsychotics are subdivided into two main categories: the first generation or typical antipsychotics, and the second generation or atypical antipsychotics.
Alright, within the brain, dopamine is found in 4 main dopamine pathways: the mesolimbic pathway, which controls motivation and desire; the mesocortical pathway, which helps regulate emotions; the nigrostriatal pathway, which contains motor neurons that bypass the medullary pyramids, to control involuntary movements and coordination; and lastly, the tuberoinfundibular pathway, which releases dopamine to limit the secretion of prolactin.

Physiology0:32–1:14

Other regions of the central nervous system that are rich in dopamine receptors include the chemoreceptor trigger zone, which initiates the vomiting reflex, and the medullary periventricular pathway, which regulates eating behavior.
However, in schizophrenia, altered levels of dopamine mainly affect the mesolimbic pathway and mesocortical pathway. There’s usually high levels of dopamine in the mesolimbic pathway which cause positive symptoms of schizophrenia, such as delusions, hallucinations, and disorganized thought.

Pathology1:14–1:48

On the other hand, low levels of dopamine in the mesocortical pathway cause negative symptoms of schizophrenia, such as lack of motivation, social withdrawal, and “flat affect,” which basically means a lack of emotions.When it comes to treating schizophrenia, some typical antipsychotics like haloperidol, trifluoperazine, and fluphenazine have a higher potency, which means you need less of it to achieve a therapeutic effect.

Mechanism of Action1:48–2:29

The lower potency antipsychotics include thioridazine and chlorpromazine and they require larger doses to achieve the same therapeutic effect as high-potency antipsychotics.
Now, in conditions such as schizophrenia, typical antipsychotics block dopamine D2 receptors in the mesolimbic pathway, which alleviates positive symptoms of schizophrenia.
However, they also block dopamine receptors in the mesocortical pathway, which might actually worsen the negative symptoms.

Indications2:29–2:56

Other psychiatric indications include psychosis, delirium, bipolar disorder, obsessive-compulsive disorder, Tourette syndrome, and Huntington disease.
Aside from their use in psychiatric disorders, blocking dopamine receptors in the chemoreceptor trigger zone can also decrease nausea and vomiting, while blocking histamine H1 receptors can have an antipruritic and sedative effect.Alright, moving on to side effects.

Side effects2:56–6:25

In the tuberoinfundibular pathway, they stimulate the release of prolactin, causing oligomenorrhea, galactorrhea, and gynecomastia; and lastly, in the nigrostriatal pathway, they cause extrapyramidal symptoms, which usually involve abnormal movements.
Let’s start with dystonia, which can occur within a few hours to days of treatment, and includes muscle spasms of the tongue, face, neck, and back.
It also causes oculogyric crisis, which is a spasm of the extraocular muscles, causing an upward and outward position of the eyes.
After a few days to a month, there could be Akathisia or pseudoparkinsonism. Akathisia is characterized by restlessness and an urge to move the limbs.
Pseudoparkinsonism is characterized by muscle rigidity, usually in the facial muscles, giving the face a wooden, mask-like appearance.
Other symptoms include bradykinesia, or slow movements, and tremors. It’s important to note that typical antipsychotics are more likely to cause these side effects compared to the atypical antipsychotics.
However, extrapyramidal symptoms usually disappear once the medication is stopped. Now, moving on to tardive dyskinesia, which can present after several months or even years; is characterized by constant involuntary, rhythmic movements.
This typically happens with the perioral muscles causing the person to repeatedly smack, or purse their lips. Unlike acute extrapyramidal symptoms, tardive dyskinesia can be irreversible, so the medication should be discontinued at the first sign of tardive dyskinesia.
Now, the most dangerous and severe extrapyramidal side effect is neuroleptic malignant syndrome or NMS, which typically starts days to weeks after starting the medications.
It’s characterized by confusion, coma, agitation, muscle rigidity, seizures, and hyperthermia. These symptoms are almost identical to serotonin syndrome, caused by antidepressants like selective serotonin reuptake inhibitors.
However, serotonin syndrome causes hyperreflexia and dilated pupils, while in neuroleptic malignant syndrome there’s hyporeflexia and normal pupils.
If this condition progresses, it will cause rhabdomyolysis, where the muscles break down. Treatment of neuroleptic malignant syndrome consists of administration of dantrolene, which is a muscle relaxant.Finally, typical antipsychotics also cause side effects by blocking other receptors: Alpha-1 receptor inhibition causes orthostatic hypotension; muscarinic receptor inhibition causes anticholinergic, or atropine-like side effects such as dry mouth, blurred vision, urinary retention, and constipation; and histamine H1 receptor inhibition causes sedation.
The low potency antipsychotics have a stronger sedating effect, but a low incidence of extrapyramidal symptoms. Other side effects include prolongation of the QT interval, and metabolic side effects, such as weight gain, dyslipidemia, and hyperglycemia.
For medicine-specific side effects, chlorpromazine causes corneal deposits, while thioridazine causes retinal deposits within the eye.

Memory Palace6:25–10:25

Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts! So, let’s visit our eccentric old aunt’s house, and she represents the older, first generation antipsychotics.
She has two dobermans by her feet since these medications act on dopamine D2 receptors. Next to her, we have a table with the high potency drugs; there’s an angel doll with a big halo, for haloperidol.
Her dream is to travel around the world and hunt for truffles, so there’s a magazine on flying planes, for fluphenazine, and a magazine on truffles for trifluoperazine.
On her other side, we have the low potency medications on the floor; let’s put a magazine about prom clothing, for chlorpromazine, and a fitness magazine with a picture of thighs, for thioridazine.
Now for the drug specific side effects, let’s put a pair of reading glasses by these 2 magazines, since they cause visual problems.
Chlorpromazine deposits in the cornea, so let’s decorate the prom dress with corns, which is super hot right now. Thioridazine deposits in the retina, which is the neural layer in the eyes, so let’s put some red nerves on the thighs.
Now for indications, our uncle is a hunter for huntington's, and he’s talking to a delivery man with a unicycle for psychosis and delirium.
Our uncle has a lot of hunting trophies, which include a brain split into two hemispheres for schizophrenia, which means “split mind.” Now, one hemisphere is bigger and it has a “+” sign on it, since these medications treat positive symptoms.
The other half is small with a “-” sign, since these medications might worsen the negative symptoms as a side effect. Next, there’s also a stuffed, two-headed polar bear, for bipolar disorder, and a tortoise for Tourette syndrome.
Outside the house, our aunt built a pyramid, for extrapyramidal side effects. The symptoms that appear early are on the top and the symptoms that appear later are on the bottom.
So at the tip, there’s a giant eyeball looking up and away for dystonia and oculogyric crisis, which can occur within hours to days.
The 2nd level is neuroleptic malignant syndrome, which typically happens within days to weeks of taking the medication. Since it’s very similar to serotonin syndrome, we’ll use the same dead knight with a few minor changes.
He’s in a death-like state, representing coma; he’s being cremated so the fire represents hyperthermia; he’s stiff, so there’s muscle rigidity; and the armor is white, for pallor.
On his chest is a broken reflex hammer, for hyporeflexia. The next level contains a restless, roaming mummy, holding an ankh for akathisia.
And he’s wearing a wooden mask representing pseudoparkinsonism. Both of these symptoms occur within days to a month.
Finally, at the bottom of the pyramide is a tarpit, for the tardive dyskinesia that can occur a month to years later. There’s a diver with just his pursed lips sticking out of the tar, gasping for breath, which represents the pursed or smacking lip motion associated with this symptom.
Now, for the other side effects, let’s put them next to the pyramide. There’s a dizzy cow, to represent orthostatic hypotension.
There’s milk leaking out of its udders, for prolactinemia. Standing by it, is an obese man eating ice cream, for hyperlipidemia and hyperglycemia.
On the other side of the pyramide is a tropical palm tree, for atropine-like side effects. Under the tree is a sleeping snake going hizzzz, for sedation caused by blocking histamine receptors.
All right, as a quick recap. First generation, or typical antipsychotics, block dopamine D2 receptors in the mesolimbic pathway, thereby alleviating the positive symptoms of schizophrenia.

Review10:25–11:28

They can also treat a number of neurological and psychiatric disorders like bipolar disorder, huntington's disease, and tourette syndrome.
High potency typical antipsychotics include haloperidol, trifluoperazine, and fluphenazine, while the low potency include thioridazine and chlorpromazine.
The major side effects are the extrapyramidal symptoms like dystonia, akathisia, and pseudoparkinsonism. The two most important ones are tardive dyskinesia, which is irreversible; and neuroleptic malignant syndrome, which is life-threatening.
Other side effects include worsening of negative symptoms in schizophrenia, hyperprolactinemia, sedation, orthostatic hypotension, and anticholinergic side effects.
wait there's more here's a mind map of all the new monix go ahead and pause the video so you can test yourself to see what you remember stay tuned for the answers after the

Mind Map11:28–11:33