Antipsychotics Flashcards
What defines a psychotic illness?
severe distortions of reality & disturbances in perception, intellectual functioning, affect, motivation, social relationships, and motor behavior
What are the positive symptoms of schizophrenia?
delucsions and hallucinations; bizarre behavior
Characteristics of patients with robust positive symptoms:
- older at first onset
- respond well to conventional antipsychotics
- onset tends to be acute
What are the negative symptoms of schizophrenia?
reduced speech, flattened affect, loss of motivation, social withdrawal and anhedonia
Definition of negative symptoms
decline in normal functions
What are the cognitive symptoms of schizophrenia?
impaired working memory, executive functioning and attention
Which symptoms are the most resistant to treatment?
negative & cognitive symptoms
Characteristics of patients with robust negative and cognitive symptoms:
- early onset
- long course of progressive deterioration (insidious onset)
When do symptoms of schizophrenia most often appear? Differences between men and women?
late teens and early 20s; after age 36 more women than men tend to experience their first episode
insidious onset
prodromal phase lasting months to years
acute onset
preciptating event such as stress or drugs
What features suggest a good prognosis?
- late onset
- clear precipitating event
- acute onset
- good support system
Environmental factors related to schizophrenia
- stress
- drug use
- gestational/birth complications: viral infections and hypoxic episodes
Where is atrophy seen in schizophrenia?
cerebrum and around the ventricles (due to loss of cells in mediodorsal nucleus of the thalamus)
What cells in schizophrenia are disorganized?
hippocampal cells
In what brain region is there decreased neurophil?
PFC
hypofrontality
reduced function of the PFC, reduced blood flow to this area indicates less gluocose being used and so less neuronal activity
Wisconsin Card Sorting Task
a cognitive task that examines executive functioning
dopamine hypothesis of schizophrenia
excess DA function results in positive symptoms of schizophrenia
evidence supporting the dopamine hypothesis of schizophrenia
- amphetamine can produce a psychotic reaction in healthy individuals, can be revered by DA antagonists
- strong correlation between D2 receptor blockade and reduction of symptoms
DA imbalance hypothesis
- reduced function of mesocortical DA neurons results in negative symptoms and cognitive dysfunction
- excess function of mesolimbic DA neurons leads to positive symptoms
Evidence supportin the DA imbalance hypothesis
- there is a decrease in the density of cortical DA nerve terminals in schizophrenia
- amphetamine can alleviate negative symptoms & cognitive dysfunction
What may result in the increase in activity of mesolimibc DA and decrease in activity of mesocortical DA neurons?
hypoactive glutamatergic neurons
Mesocortical DA pathway and glutamatergic neurons
low glutamate produces low DA release in the PFC, exacerating negative and cognitive symptoms
Glutamatergic neurons and DA mesolimbic pathway
glutamate neurons usually excite inhibitory GABA neurons that inhibit the mesolimbic pathway, thus low glutamate leads to excess DA release in the nucelus accumbens (+ symptoms)
glutamate hypothesis of schizophrenia
hypofunction of glutamate neurons is involved in both negative and positive symptoms
Evidence supporting the glutamate hypothesis of schizophrenia
- blocking NMDA receptors with PCP or ketamine produces schizophrenia symptoms and exacerbates symptoms in those with schizophrenia
- PCP & ketamine produce both the positive & negative symptoms
What is a neuroleptic?
an antipsychotic drug
What is the law of thirds?
one third of patients respond well to antipsychotics, one third shows significant improvements, but may relapse, and one third fails to respond
chlorpromazine
- first antipsychotic drug
- aka Largactil or Thorazine
What was chlorpromazine originally supposed to treat?
surgical shock, sed as an antihistamine, antiemetic and sedative
Treatments before antipsychotic medications:
- isolation or restraint
- shock therapy using insulin-induced seizures or electrical current
- prefrontal lobotomy
Phenothiazines block
the dopamine D2 receptor
D1 family of receptors:
D1 and D5 dopamine receptors
D2 family of receptors:
D2, D3 and D4
D1 family of receptors are coupled to ____, so ____ adenylate cyclase, causing —-
coupled to stimulatory G-protein; activates adenylate cyclase, causing opening of Na+ channel (depolarization)
D2 family of receptors are coupled to ____, so _____ adenylate cyclase
coupled to inhibitory G-proteins, thus inhibit adenylate cyclase
D1 family antagonists
Na+ channel will remain closed; inhibits depolarization
D2 family antagonists
Na+ channel opens, causes depolarization
strong correlation between the ability of a drug to displace a radio-labeled DA agonist and ____
average clinical daily dose
antipsychotics also bind to:
5-HT, NE, histamine and D1 receptors, but there is no clear relationship between clinical effectiveness and binding to these receptors
