Flashcards in Neuropharmacology: Antipsychotics Deck (19):
What are some current theories about biological causes of psychosis?
excess dopamine or serotonin influence. drugs that block these receptors may are antipsychotic
What are the 3 most important locations of DA?
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
What DA receptors are inhibitory and what DA receptors are excitatory?
excitatory: D1 and D5
What are the serotonergic pathways in the brain
from the Raphe nuclei
descending fibers to cerebellum and spinal cord
asecnding fibers that go throughout the cortex, including the hippocampus
What are the physiological and pharmacological differences seen in schizophrenia?
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.
What areht epost-morthem changes in pts with schizophrenia?
neuronal loss without gliosis (not a new process)
loss of GABAergic interneurons
What is the DA hypothesis and what are its flaws?
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.
What do atypical antipsychotics do?
block DA receptors selectively and also block 5HT receptors.
Why do we think 5HT is involved in psychosis?
excess serotonin may incr. DA activity and LSD, which is a serotonin agonist, produces hallucinations.
What is the potential role of glutamate in psychosis?
PCP and ketamine block NMDA receptors and exacerbate psychotic symptoms. not enough glutamate may cause psychosis.
What are the therapeutic targets for antipsychotic agents? What are the receptors causing some of the side effects?
D2 and D4 receptors in the limbic and cortical areas and 5HT2 receptors.
side effects caused by blocking D2 and D3 in the striatum.
What are the classic anti-psychotic drugs?
What are the newer atypical antipsychotics?
clozapine (clozaril), risperidone, olanzapine (zyprexa), quetiapine (seroquel)
What are advantages of atypical antispychotics?
fewer extrapyramidal side effects because DA selective
greater efficacy for negative symptoms
lesser anticholinergic and anti-histamine affects
What are the specific actions of clozapine, risperidone. olanzapine, and quetiapine?
clozapine, risperidone, and olanzapine: block 5HT receptors and D2 receptors
quetiapine: blocks at least 2 5HT receptor subtypes
What are some effects of the antipsychotics on the neocortex and limbic cortex?
sedation lower seizure threshold, improved thought
What are some effects of the antipsychotics on the basal ganglia?
reduced operant behavior, slowed action and responses, cataleptic immobility (Parkinsonism), dyskinesias
What are some effects of the antipsychotics on the hypothalamus/endocrine system?
increased prolactin secretion- very annoying side effect
altered temperature regulation and increased risk of malignant hyperthermia