Antipsychotics

Question 1

What defines a psychotic illness?

Answer 1

severe distortions of reality & disturbances in perception, intellectual functioning, affect, motivation, social relationships, and motor behavior

Question 2

What are the positive symptoms of schizophrenia?

Answer 2

delucsions and hallucinations; bizarre behavior

Question 3

Characteristics of patients with robust positive symptoms:

Answer 3

• older at first onset
• respond well to conventional antipsychotics
• onset tends to be acute

Question 4

What are the negative symptoms of schizophrenia?

Answer 4

reduced speech, flattened affect, loss of motivation, social withdrawal and anhedonia

Question 5

Definition of negative symptoms

Answer 5

decline in normal functions

Question 6

What are the cognitive symptoms of schizophrenia?

Answer 6

impaired working memory, executive functioning and attention

Question 7

Which symptoms are the most resistant to treatment?

Answer 7

negative & cognitive symptoms

Question 8

Characteristics of patients with robust negative and cognitive symptoms:

Answer 8

• early onset

- long course of progressive deterioration (insidious onset)

Question 9

When do symptoms of schizophrenia most often appear? Differences between men and women?

Answer 9

late teens and early 20s; after age 36 more women than men tend to experience their first episode

Question 10

insidious onset

Answer 10

prodromal phase lasting months to years

Question 11

acute onset

Answer 11

preciptating event such as stress or drugs

Question 12

What features suggest a good prognosis?

Answer 12

• late onset
• clear precipitating event
• acute onset
• good support system

Question 13

Environmental factors related to schizophrenia

Answer 13

• stress
• drug use
• gestational/birth complications: viral infections and hypoxic episodes

Question 14

Where is atrophy seen in schizophrenia?

Answer 14

cerebrum and around the ventricles (due to loss of cells in mediodorsal nucleus of the thalamus)

Question 15

What cells in schizophrenia are disorganized?

Answer 15

hippocampal cells

Question 16

In what brain region is there decreased neurophil?

Answer 16

PFC

Question 17

hypofrontality

Answer 17

reduced function of the PFC, reduced blood flow to this area indicates less gluocose being used and so less neuronal activity

Question 18

Wisconsin Card Sorting Task

Answer 18

a cognitive task that examines executive functioning

Question 19

dopamine hypothesis of schizophrenia

Answer 19

excess DA function results in positive symptoms of schizophrenia

Question 20

evidence supporting the dopamine hypothesis of schizophrenia

Answer 20

• 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

Question 21

DA imbalance hypothesis

Answer 21

• reduced function of mesocortical DA neurons results in negative symptoms and cognitive dysfunction
• excess function of mesolimbic DA neurons leads to positive symptoms

Question 22

Evidence supportin the DA imbalance hypothesis

Answer 22

• there is a decrease in the density of cortical DA nerve terminals in schizophrenia
• amphetamine can alleviate negative symptoms & cognitive dysfunction

Question 23

What may result in the increase in activity of mesolimibc DA and decrease in activity of mesocortical DA neurons?

Answer 23

hypoactive glutamatergic neurons

Question 24

Mesocortical DA pathway and glutamatergic neurons

Answer 24

low glutamate produces low DA release in the PFC, exacerating negative and cognitive symptoms

Question 25

Glutamatergic neurons and DA mesolimbic pathway

Answer 25

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)

Question 26

glutamate hypothesis of schizophrenia

Answer 26

hypofunction of glutamate neurons is involved in both negative and positive symptoms

Question 27

Evidence supporting the glutamate hypothesis of schizophrenia

Answer 27

• 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

Question 28

What is a neuroleptic?

Answer 28

an antipsychotic drug

Question 29

What is the law of thirds?

Answer 29

one third of patients respond well to antipsychotics, one third shows significant improvements, but may relapse, and one third fails to respond

Question 30

chlorpromazine

Answer 30

• first antipsychotic drug

- aka Largactil or Thorazine

Question 31

What was chlorpromazine originally supposed to treat?

Answer 31

surgical shock, sed as an antihistamine, antiemetic and sedative

Question 32

Treatments before antipsychotic medications:

Answer 32

• isolation or restraint
• shock therapy using insulin-induced seizures or electrical current
• prefrontal lobotomy

Question 33

Phenothiazines block

Answer 33

the dopamine D2 receptor

Question 34

D1 family of receptors:

Answer 34

D1 and D5 dopamine receptors

Question 35

D2 family of receptors:

Answer 35

D2, D3 and D4

Question 36

D1 family of receptors are coupled to ____, so ____ adenylate cyclase, causing —-

Answer 36

coupled to stimulatory G-protein; activates adenylate cyclase, causing opening of Na+ channel (depolarization)

Question 37

D2 family of receptors are coupled to ____, so _____ adenylate cyclase

Answer 37

coupled to inhibitory G-proteins, thus inhibit adenylate cyclase

Question 38

D1 family antagonists

Answer 38

Na+ channel will remain closed; inhibits depolarization

Question 39

D2 family antagonists

Answer 39

Na+ channel opens, causes depolarization

Question 40

strong correlation between the ability of a drug to displace a radio-labeled DA agonist and ____

Answer 40

average clinical daily dose

Question 41

antipsychotics also bind to:

Answer 41

5-HT, NE, histamine and D1 receptors, but there is no clear relationship between clinical effectiveness and binding to these receptors