Antipsicóticos atípicos (2a geração) | Aula 27 | Farmacologia do SNC rápida e fácil

Summary

This video lesson covers second-generation antipsychotics (SGAs), their development, and their therapeutic uses. SGAs, developed to reduce the neurological side effects of first-generation antipsychotics, are now widely used in treating schizophrenia, bipolar disorder, and depression. Despite their effectiveness, they come with a range of metabolic and other side effects like weight gain, sedation, and increased risk of diabetes. The video explores their mechanisms of action, including serotonin receptor antagonism, and highlights specific medications like clozapine, quetiapine, and risperidone. Viewers will also learn about potential adverse effects, including neutropenia and extrapyramidal symptoms, and how to monitor these risks in clinical practice.

Takeaways

• 😀 Second-generation antipsychotics, also known as atypical antipsychotics, were developed to reduce the neurological side effects seen in first-generation antipsychotics.
• 😀 The prototype of second-generation antipsychotics was clozapine, which was discovered in 1959. It was considered atypical due to its reduced extrapyramidal side effects compared to first-generation drugs.
• 😀 Despite being the first second-generation antipsychotic, clozapine still presents a range of adverse effects, which led to the development of other drugs with improved side effect profiles.
• 😀 Popular second-generation antipsychotics include clozapine, quetiapine, risperidone, olanzapine, and aripiprazole. These drugs are more commonly prescribed than first-generation ones.
• 😀 The mechanism of action of second-generation antipsychotics involves blocking D2 dopamine receptors, particularly in the mesolimbic pathway. They also antagonize serotonin receptors, which may play a more significant role in their effects than D2 blockade.
• 😀 Second-generation antipsychotics are generally effective in treating both positive symptoms (e.g., delusions, hallucinations) and negative symptoms (e.g., apathy, lack of energy) of schizophrenia.
• 😀 These antipsychotics are also used in the treatment of resistant depression, bipolar disorder (both manic and depressive episodes), and sometimes in the management of agitation in autism spectrum disorder.
• 😀 Common side effects of second-generation antipsychotics include sedation, orthostatic hypotension (low blood pressure when standing), and anticholinergic effects like dry mouth and constipation.
• 😀 Metabolic side effects are more prominent with second-generation antipsychotics, including weight gain, dyslipidemia, and diabetes. Clozapine and olanzapine have higher risks for these issues.
• 😀 Clozapine specifically has severe side effects such as neutropenia (low white blood cell count), myocarditis, and cardiomyopathy. Patients on clozapine must have regular blood tests to monitor white blood cell levels.
• 😀 Although second-generation antipsychotics have a lower risk of extrapyramidal symptoms compared to first-generation drugs, they can still cause these side effects, with risperidone being more associated with them.
• 😀 Elevated prolactin levels and the risk of neuroleptic malignant syndrome are also possible with second-generation antipsychotics, though these are more common with first-generation drugs.

Q & A

What was the main reason second-generation antipsychotics (SGAs) were developed?

SGAs were developed to reduce the neurological side effects (specifically extrapyramidal symptoms) seen with first-generation antipsychotics (FGAs).

How did clozapine, the prototype of second-generation antipsychotics, differ from first-generation antipsychotics?

Clozapine was considered an atypical antipsychotic because it caused fewer extrapyramidal side effects at the same doses compared to FGAs, making it the first attempt to improve the side effect profile of antipsychotic medications.

What are the common second-generation antipsychotics mentioned in the video?

Common second-generation antipsychotics include clozapine, quetiapine, risperidone, olanzapine, aripiprazole, ziprasidone, lurasidone, and paliperidone.

What is the primary mechanism of action for second-generation antipsychotics?

Second-generation antipsychotics primarily block dopamine D2 receptors in the brain, but they also antagonize serotonin receptors (5-HT2A), which appears to play a larger role in their therapeutic effects. Additionally, they may block histamine (H1), alpha-adrenergic, and muscarinic receptors.

What therapeutic conditions are second-generation antipsychotics used to treat?

Second-generation antipsychotics are primarily used to treat schizophrenia, bipolar disorder, and in some cases, depression (as adjunctive treatment). They are also used for managing agitation and irritability in children with autism and for certain behavioral issues in Alzheimer's disease.

What are some of the common metabolic side effects associated with second-generation antipsychotics?

Common metabolic side effects include weight gain, increased appetite, dyslipidemia (abnormal lipid levels), and diabetes. These effects are more pronounced with medications like clozapine and olanzapine, while ziprasidone has a lower risk of these effects.

Which second-generation antipsychotics are most likely to cause sedation?

Sedation is most commonly associated with clozapine and quetiapine, as these drugs antagonize histamine receptors (H1).

What is orthostatic hypotension, and which antipsychotics are more likely to cause it?

Orthostatic hypotension refers to a sudden drop in blood pressure when standing up, leading to dizziness or fainting. Second-generation antipsychotics like clozapine and olanzapine are more likely to cause this, especially during the early stages of treatment or when doses are increased.

What are some of the common anticholinergic side effects seen with second-generation antipsychotics?

Anticholinergic side effects include dry mouth, constipation, blurred vision, and urinary retention. Clozapine has the highest affinity for muscarinic receptors, so it is more likely to cause these effects.

Why is regular blood monitoring important for patients on clozapine?

Patients taking clozapine need regular blood monitoring because clozapine can cause neutropenia, a condition where white blood cell counts drop, increasing the risk of infections.

What serious cardiovascular side effects are associated with clozapine?

Clozapine is associated with serious cardiovascular risks, including myocarditis (inflammation of the heart muscle) and cardiomyopathy (heart muscle disease), especially during the early months of treatment.

How do second-generation antipsychotics compare to first-generation antipsychotics in terms of extrapyramidal symptoms?

Second-generation antipsychotics generally have a lower risk of causing extrapyramidal symptoms (movement disorders) compared to first-generation antipsychotics. However, the risk is not entirely eliminated, and drugs like risperidone can still cause these symptoms.