Antipsychotic Drugs

Question 1

Arises in the ventral tegmental area (VTA)

Projects to the frontal cortex (cortical limb)
Too little DA activity (negative and cognitive symptoms)
Do not want to block DA receptors here

Projects to the nucleus accumbens (limbic limb)
Too much dopaminergic activity (positive symptoms)
Want to block DA receptors here

Mesocorticolimbic projection is involved in schizophrenia

Answer 1

Mesocorticolimbic projection

Question 2

Blockade of D2 receptors in the striatum produces parkinsonian-like effects (extrapyramidal symptoms)

Do not want to block DA receptors here

Answer 2

Nigrostriatal projection

Question 3

Arcuate nucleus of the hypothalamus pituitary

Endocrinological side effects due to D2 block in this location
DA suppresses prolactin, blocking D2 increases prolactin

Answer 3

Tuberoinfundibular system

Question 4

Motor nucleus of the vagus areas around ventricles

Deals with eating behavior, blockade is associated with weight gain

Answer 4

Medullary-periventricular neurons

Question 5

blockage results in antiemetic properties

Answer 5

dopamine receptors in chemotrigger zone

Question 6

Typical phenothiazine antipsychotic
First agent to specifically address psychosis as opposed to simple sedation
Potentiates anesthesia
No longer often used but may be used in acute treatment of psychotic episode
Sedation, alpha 1 block (bad in the elderly)
Skin reactions, photosensitivity, cardiotoxicity, anticholinergics
Increased risk of tardive dyskinesia

Answer 6

chlorpromazine

Question 7

Typical butyrophenone antipsychotic 
Major drug in schizophrenia treatment
Lower sedation and less alpha block than phenothiazines 
Parenteral form available
Severe extrapyramidal symptoms

Answer 7

haloperidol

Question 8

First atypical antipsychotic
No extrapyramidal symptoms due to DPI selectively in mesolimbic pathway
High potency at 5HT2, better against negative symptoms than typicals
No D2 super-sensitivity
Agranulocytosis and diabetes risk, weight gain
Anticholinergic effects can cause confusion, dry mouth, orthostatic hypotension, urinary

Answer 8

clozapine

Question 9

Atypical antipsychotic
Low risk of extrapyramidal symptoms with low doses
No evidence of agranulocytosis risk

Answer 9

risperidone

Question 10

Atypical antipsychotic
No evidence of agranulocytosis risk
Associated with weight gain, risk of diabetes, and hyoptension
Smaller increase in serum prolactin that with haloperidol
Anticholinergic effects can cause confusion, dry mouth, urinary retention, constipation, blurred vision

Answer 10

olanzepine

Question 11

Atypical antipsychotic

QT prolongation

Answer 11

ziprasidone

Question 12

Atypical antipsychotic
Partial agonist at D2
Modest affinity at 5HT2 receptors (antagonist)
Partial agonist at 5HT1A receptors
No apparent risk of diabetes, lesser effect on prolactin levels
Used when depressive symptoms are present

Answer 12

aripiprazole

Question 13

early neurological side effect of antipsychotics
Appears in 1-5 days
Anticholinergics are diagnostic and curative
Readily treatable but alarming to patient

Answer 13

acute dystonia (spastic retrocollis or torticollis)

Question 14

early neurological side effect of antipsychotics
Occurs in 5-60 days
Reduce drug or change treatment
Anticholinergic or propranolol may help
Occurs early, tends to persist

Answer 14

akasthisia (motor restlessness)

Question 15

early neurological side effect of antipsychotics
Occurs in 5-30 days of treatment
Bradykinesia, rigidity, mask facies, shuffling gait
Caused by antagonism of DA in striatum
Can treat with anticholinergics

Answer 15

parkinsonism (EPS)

Question 16

early neurological side effect of antipsychotics
Catatonia, stupor, fever, unstable blood pressure, myoglobinemia
May be fatal
Can occur within weeks, and can persist after stopping treatment likely due to D2 block in the hypothalamus
Stop drug immediately, high mortality
Bromocriptine or dantrolene may help
Do not use anticholinergics

Answer 16

neuroleptic malignant syndrome

Question 17

early neurological side effect of antipsychotics
Especially with low potency antipsychotics and clozapine
Use with caution in epilepsy and patient withdrawing from CNS depressant

Answer 17

lower seizure threshold

Question 18

late neurological side effect of antipsychotics
May be a late variant of Parkinsonism
Can occur after months or years of treatment
Mechanism is unknown
Antiparkinson drugs are not often helpful

Answer 18

perioral syndrome (rabbit syndrome)

Question 19

late neurological side effect of antipsychotics
Oral facial dyskinesias, widespread chorioathetosis or dystonia
Occurs after months or years of treatment
Occurs in 20% of patients
Mechanism is dopamine receptor supersensitivity due to prolonged D2 block
Increased DA sensitivity increases GABA inhibition which increases movement
Prevention is crucial, treatment is unsatisfactory
Do not use anticholinergics

Answer 19

tardive dyskinesia