PSYCH - Anti-psychotics

Question 1

Schizophrenics have high rates of:

Answer 1

suicide attempts 10% of schizophrenic population
suicide rates 10%
substance abuse (50% of schizophrenic population)

Question 2

What is the Neurodevelopmental Model of Schizophrenia?

Answer 2

mesolimbic activity due to:

• underdevelopment of the pre-frontal cortex
• inadequate regulation of pre-frontal cortex (mostly GABA)

Question 3

What is the Kindling Model of Schizophrenia

Answer 3

hyperactive dopamine system gets even more hyperactive overtime due to resetting of the baseline level (dopamine system sensitization); may be why bipolar disorder episodes tend to get worse over time “kindled the system”

Question 4

What is the Neurodegenerative Model of Schizophrenia

Answer 4

areas of enlarged ventricles + dysfunction

Question 5

How does phencyclidine cause schizophrenia-like symptoms (psychosis)?

Answer 5

it is a hallucinogen that causes psychosis that never goes away. It acts as a NMDA receptor antagonist, which causes excess glutamate release through non-NMDA systems, thereby producing a excitotoxicity that results in + and - symptoms and cognitive deficits

Question 6

HYPERactivity of the mesolimbic system results in:

HYPOactivity of the mesocortical system results in:

Answer 6

HYPER of ML –> Positive symptoms (hallucinations, delusions, thought, movement disorders)

HYPO of MC –> Negative symptoms (lack of affect, pleasure)

Question 7

What are the limitations of 1st generation anti-psychotic drugs?

Answer 7

they’re effective, but tolerance can develop and may be a reason why relapse is commonly seen

Question 8

What is the dopamine hypothesis of schizophrenia?

Answer 8

model that attributes the symptoms of schizophrenia (ie psychoses) to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine-receptor antagonistic effects

Question 9

1st generation anti-psychotics used to treat schizophrenia usually treat ________ symptoms, but have minimal effects on the ________ and ________

Answer 9

treats: positive symptoms

minimal effects on: negative symptoms and cognitive improvements

Question 10

What are common side effect of 1st generation antipsychotics? (5)

Answer 10

Increase in prolactin levels

• breast cancer
• osteoporosis
• cardiovascular disorders
• sexual disturbances

Increase in extrapyramidal signaling:
- acute dystonia (neuroleptic malignant syndrome, muscle spasms)

• parkinsonism (bradykinesia, rigidity, variable tremora, mask facies)
• akathesia (inability to sit still or remain motionless)
• tardive dyskinesia (dyskinesia of the lower face, choreoathetosis)

Question 11

What is the neuroleptic malignant syndrome (NMS)?

Answer 11

if 1st generation anti-psychotics are given too quickly, esp. in young men who are muscular, they can develop NMS.

Major manifestations:

• Fever
• Muscle rigidity
• Cognitive changes (Delirium)
• Elevated CPK levels (breakdown of muscle)

Fatality rate: 20%

Question 12

What is the best new (atypical) antipsychotic drug on the market? Why?

Mechanism of action: 
Side Effects: 
Effects on Extrapyramidal symptoms: 
Effects on prolactin secretion: 
Outcome of drug:

Answer 12

Mechanism
- potent blocker 5HT and a2 receptors (dramatic NE release), and weak blocker of D2 receptor

EPS:
- minimal EPS effects

Prolactin:
- minimal PRL elevation

outcome: decreased substance abuse, decreased suicidality

side effects:

• agranulocytosis
• weight gain
• seizures
• myocarditis
• tachycardia
• hypertension or hypotension
• drooling
• sedation
• liver function changes

Question 13

Old anti-psychotics increase prolactin levels. Why is this a problem?

Answer 13

Elevated prolactin levels may play important roles, both direct and indirect, in various pathologic states, including

• breast cancer
• osteoporosis
• cardiovascular disorders
• sexual disturbances

Question 14

Olanzapine

Mechanism of action:
Effects on Extrapyramidal symptoms:
Effects on prolactin secretion:
Side Effects:

Answer 14

Mechanism of action
- blocks 5HT/D2 receptors

EPS effects
- low

Prolactin effects:
- low

Side effects

• weight gain
• glucose/lipid dysregulation
• sedation

Question 15

Aripiprazole

Mechanism of action:
Effects on Extrapyramidal symptoms:
Effects on prolactin secretion:
Side Effects:

Answer 15

Mechanism of action
- high affinity partial dopamine agonist

EPS effects
- minimal

Prolactin effects:
- none

Side effects

• low weight gain
• insomnia

Question 16

What is the difference between Olanzapine and Aripiprazole in terms of wakefulness?

Answer 16

Olanzapine - sedative

Aripiprazole - insomnia

Question 17

What is the mechanism of novel/atypical anti-psychotics?

Answer 17

it causes release of dopamine in the pre-frontal cortex, which improves the functioning.

Question 18

What’s the difference between 1st generation anti-psychotics and novel aytpical anti-psychotics in terms of relapses and tolerance?

Answer 18

1st generation anti-psychotics: tolerance can develop, relapses are common

novel aytpical anti-psychotics: tolerance does not develop, fewer relapses

Question 19

What’s the difference between 1st generation anti-psychotics and novel aytpical anti-psychotics in terms of their effects on + and - symptoms of schizophrenia?

Answer 19

1st generation anti-psychotics: effects on + symptoms only, minimal effects on - symptoms

novel aytpical anti-psychotics: effects on + and some - symptoms

Question 20

What’s the difference between 1st generation anti-psychotics and novel aytpical anti-psychotics in terms of their effects on extrapryamidal symptoms and prolactin levels?

Answer 20

1st generation anti-psychotics: high EPS + high Prolactin levels

novel aytpical anti-psychotics: low EPS + low prolactin levels