Chapter 5 (Antipsychotics)

Question 1

Typical antipsychotics are often called “neuroleptics” because….

Answer 1

In animal studies, it was noted that they caused “neurolepsis” (indifference, slowness, absence of motor activity). In humans this is psychomotor retardation, emotional quieting, and affective indifference

Question 2

D2 receptors are blocked by typical antipsychotics primarily in which pathway?

Answer 2

Mesolimbic dopamine pathway (which is hyperactive in untreated schizophrenia)

Question 3

Side effects come from blocking D2 receptors where?

Answer 3

Everywhere but the mesolimbic dopamine pathway

Question 4

What % of D2 receptors must be blocked to reach therapeutic effect with typical antipsychotics? When do side effects kick in?

Answer 4

For most conventional antipsychotics, the degree of D2 receptor binding in the mesolimbic pathway needed for antipsychotic effects is close to 80%, while D2 receptor occupancy greater than 80% in the dorsal striatum is associated with extrapyramidal side effects (EPS) and in the pituitary is associated with hyperprolactinemia.

Question 5

Typical antipsychotics can worsen negative sx via what pathway?

Answer 5

In untreated schizophrenia, the mesocortical dopamine pathways to dorsolateral prefrontal cortex (DLPFC) and to ventromedial prefrontal cortex (VMPFC) are hypothesized to be hypoactive. Typical antipsychotics can further slow these down, worsening cognitive and negative symptoms.

Question 6

EPS comes from which pathway?

Answer 6

The nigrostriatal dopamine pathway is theoretically unaffected in untreated schizophrenia. However, blockade of D2 receptors prevents dopamine from binding there and can cause EPS.

Question 7

Tardive Dyskinesia come from….?

Answer 7

Chronic blockade of the nigrostriatal dopamine pathway leading to up regulation of dopamine receptors in that region.

Question 8

Elevated prolactin come from which pathway?

Answer 8

The tuberoinfundibular dopamine pathway, which projects from the hypothalamus to the pituitary gland, is theoretically “normal” in untreated schizophrenia. D2 antagonists reduce activity in this pathway by preventing dopamine from binding to D2 receptors. This causes prolactin levels to rise.

Question 9

Reward system of the brain is through which pathway?

Answer 9

D2 receptors in the mesolimbic dopamine system are postulated to mediate not only the positive symptoms of psychosis, but also the normal reward system of the brain, and the nucleus accumbens is widely considered to be the “pleasure center” of the brain .

Question 10

This % of patients will get Tardive Dyskinesia while taking typical antipsychotics…

Answer 10

5% per year