Typical antipsychotics

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. 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. 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. 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.

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. 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.