Neuropharmacology: Antipsychotics

Question 1

What are some current theories about biological causes of psychosis?

Answer 1

excess dopamine or serotonin influence. drugs that block these receptors may are antipsychotic

Question 2

What are the 3 most important locations of DA?

Answer 2

within the hypothalamus, it inhibits prolactin release
in the striatum and cortical regions and substantia nigra
in the medulla as part of the chemoreceptor trigger zone

Question 3

What DA receptors are inhibitory and what DA receptors are excitatory?

Answer 3

inhibitory: D2-4
excitatory: D1 and D5

Question 4

What are the serotonergic pathways in the brain

Answer 4

from the Raphe nuclei
descending fibers to cerebellum and spinal cord
asecnding fibers that go throughout the cortex, including the hippocampus

Question 5

What are the physiological and pharmacological differences seen in schizophrenia?

Answer 5

reduced blood flow to prefrontal, cingluate, and temporal cortex. Decreased metabolic activity in the frontal area (correlates esp. with negative symptoms). Decresae in hippocampus (correlates with hallucinations). Increased DA receptors in the caudate.

Question 6

What areht epost-morthem changes in pts with schizophrenia?

Answer 6

neuronal loss without gliosis (not a new process)

loss of GABAergic interneurons

Question 7

What is the DA hypothesis and what are its flaws?

Answer 7

DA hypothesis: anti-DA receptor drugs reduce psychosis, so maybe DA is responsible for psychotic symptoms.
flaws: different kids of DA receptors- not all equivalent. D1 and D5 are excitatory (incr. adenylate cyclase) and are differentially distributed- lots of D1 in the striatum.
D2,3,4: inhibit adenylate cyclase. D2 mostlin in striatum, neocortex, and limbic cortex.

Question 8

What do atypical antipsychotics do?

Answer 8

block DA receptors selectively and also block 5HT receptors.

Question 9

Why do we think 5HT is involved in psychosis?

Answer 9

excess serotonin may incr. DA activity and LSD, which is a serotonin agonist, produces hallucinations.

Question 10

What is the potential role of glutamate in psychosis?

Answer 10

PCP and ketamine block NMDA receptors and exacerbate psychotic symptoms. not enough glutamate may cause psychosis.

Question 11

What are the therapeutic targets for antipsychotic agents? What are the receptors causing some of the side effects?

Answer 11

D2 and D4 receptors in the limbic and cortical areas and 5HT2 receptors.
side effects caused by blocking D2 and D3 in the striatum.

Question 12

What are the classic anti-psychotic drugs?

Answer 12

chlorpromazine (thorazine)
thioridazine
haloperidol

Question 13

What are the newer atypical antipsychotics?

Answer 13

clozapine (clozaril), risperidone, olanzapine (zyprexa), quetiapine (seroquel)

Question 14

What are advantages of atypical antispychotics?

Answer 14

fewer extrapyramidal side effects because DA selective
greater efficacy for negative symptoms
lesser anticholinergic and anti-histamine affects

Question 15

What are the specific actions of clozapine, risperidone. olanzapine, and quetiapine?

Answer 15

clozapine, risperidone, and olanzapine: block 5HT receptors and D2 receptors
quetiapine: blocks at least 2 5HT receptor subtypes

Question 16

What are some effects of the antipsychotics on the neocortex and limbic cortex?

Answer 16

sedation lower seizure threshold, improved thought

Question 17

What are some effects of the antipsychotics on the basal ganglia?

Answer 17

reduced operant behavior, slowed action and responses, cataleptic immobility (Parkinsonism), dyskinesias

Question 18

What are some effects of the antipsychotics on the hypothalamus/endocrine system?

Answer 18

increased prolactin secretion- very annoying side effect

altered temperature regulation and increased risk of malignant hyperthermia

Question 19

What are some effects of the antipsychotics on the brainstem?

Answer 19

anti-emesis
hypothension
blurred vision
sedation
hypothension from affects on the autonomics