Antipyschotics

Question 1

what are the four dopamine pathways in the brain

Answer 1

• mesolimbic pathway
• nigrostriatal pathway
• mesocortical pathway
• tuberoinfundibular pathway

Question 2

explain the mesolimbic and nigrostriatal pathway in terms of schizophrenia

Answer 2

• hyperactivity in the mesolimbic pathway account for the positive psychotic symptoms so blocking D2 receptors alleviates the positive psychotic symptoms
• nigrostriatal pathway controls motor movement –> blocking D2 receptors –> extrapyramidal reactions –> acute dystonia, akathisia (uncontrollable restlessness), parkinsonian like symptoms (bradykinesia, tremors, rigidity)

Question 3

explain the mesocortical and tuberoinfundibular pathway

Answer 3

• reduced activity in mesocortical –> negative psychotic symptoms –> blockade of D2 receptors in this pathway –> cause or worsen negative symptoms such as emotional blunting and cognitive problems
• dopamine released from tuberoinfundibular pathway inhibits prolactin secretion –> blockade of D2 receptors –> increase in prolactin –> galactorrhea

Question 4

what are the classical antipsychotics and how are they sub classified

Answer 4

high potency: Haloperidol and Fluphenazine

low potency: Chlorpromazine and Thioridazine

Question 5

what does it mean to be a high potency and low potency antipsychotic

Answer 5

• high potency: haloperidol and fluphenazine are more likely to produce extrapyramidal symptoms because of higher affinity for D2 receptors
• low potency: Chlorpromazine and Thioridazine are less likely to produce extrapyramidal symptoms and more likely to produce sedation and postural hypotension

Question 6

what are the atypical antipsychotics

Answer 6

CROAQ

Clozapine
Risperidone
Olanzapine
Aripiprazole
Quetiapine

Question 7

mechanism of classical antipsychotics (name them)

Answer 7

high: haloperidol and fluphenazine
low: chlorpromazine and thioridazine

block dopamine receptors in the brain and in the periphery

Question 8

what are the D1-like and D2-like dopamine receptors and what type of G proteins do they use for their mechanism

Answer 8

D1 like dopamine receptors: D1 and D5 –> Gs and they activate adenylyl cyclase

D2 like dopamine receptors: D2, D3, D4 –> Gi and they inhibit adenylyl cyclase

Question 9

receptors does clozapine have a high affinity towards

Answer 9

D1, D2, D4, 5HT-2, muscarinic, and alpha adrenergic

Question 10

receptors does risperidone have a high affinity towards

Answer 10

higher affinity towards 5-HT2 than D2

Question 11

what are common properties of atypical antipsychotics

Answer 11

• dual antagonism for 5-HT2A and D2
• exert part of their action by antagonizing 5-HT
• less likely to have extrapyramidal reactions than the classical agents
• less likely to have tardive dyskinesia
• less likely to increase prolactin
• more effective at treating negative symptoms
• effective in treatment of refractory population

Question 12

mechanism of action of Aripiprazole

Answer 12

• partial agonist at 5-HT1A and D2

- antagonist at 5-HT2A

Question 13

How do most of the antipsychotics have anti emetic effect and what are the exceptions

Answer 13

• anti emetic effect due to blockade of D2 receptors

- exception is Aripiprazole (agonist at D2) and Thioridazine

Question 14

what antipsychotics are used to treat outpatients and individuals who are not compliant with medication

Answer 14

Fluphenzine decanoate
Risperidone decanoate
Haloperidol decanoate

they are all slow releasing formulations

Question 15

why are low potency classical agents less likely to have extrapyramidal reactions (name them)

Answer 15

Chlorpromazine and Thioridazine

less affinity for D2 receptors and have stronger anti cholinergic effects (hence why they are more likely to have sedation and postural hypotension)

Question 16

what can the parkinsonism seen as side effects of anti psychotics be treated with

Answer 16

Benztropine and Trihexyphenidyl

-together with diphenhydramine and amantadine

Question 17

what should not be used to treat parkinsonism

Answer 17

levodopa

Question 18

what can acute dystonia be treated with

Answer 18

benztropine, trihexyphenidyl, diphenhydramine

Question 19

what is used to manage akathisia (uncontrolled restlessness)

Answer 19

• reduced dosage of anti pyschotics
• Clonazepam
• Propanolol

Question 20

Used to treat patients with tardive dyskinesia who require antipsychotics

Answer 20

Clozapine

Question 21

steps taken when tardive dyskinesia is diagnosed/seen in patient taking anti psychotics

Answer 21

First, this is due to upregulation of dopamine receptors due to its blockade

• discontinue antipsychotics
• stop anti cholinergic drugs
• stop anti parkinsonism drugs
• stop TCAs

Question 22

AE of antipsychotics

Answer 22

NESS

Neuroleptic Malignant Syndrome
Extrapyramidal reactions
Seizures
Sedation

Question 23

What is neuroleptic malignant syndrome

Answer 23

• results from excessively rapid blockade of dopamine receptors
• characterized by severe rigidity, tremor, hyperthermia, altered mental status, autonomic instability, elevated WBC, elevated serum creatine kinase

Question 24

what can be used to treat neuroleptic malignant syndrome

Answer 24

Dantrolene

Bromocriptine

Question 25

which of the antipsychotics is associated with agranulocytosis and how is it monitored

Answer 25

Clozapine patients must get weekly blood count for first 6 months of treatments then every 3 weeks thereafter

Question 26

endocrine side effects of antipsychotics

Answer 26

hyperglycemia and diabetes

Question 27

only antipsychotic to cause retinal deposit resembling retinitis pigmentosa

Answer 27

Thioridazine

Question 28

other AE of antipsychotics

Answer 28

Drowsiness Jaundice Poikilothermia

Question 29

uses of anti psychotics

Answer 29

``` Schizophrenia Bipolar Disorder Tourette's disorder Alzheimer's Treatment resistant major depression Psychotic depression ```

Question 30

non psychiatric uses of anti psychotics

Answer 30

nausea and vomiting (blockade of D receptors) | Neuroleptanesthesia (droperidol)

Question 31

drug of choice for psychotics and why

Answer 31

atypical drugs preferred due to benefit for negative symptoms, less EPR, less tardive dyskinesia, less increase in prolactin increase

Question 32

what is Clozapine reserved for and why

Answer 32

Refractory patients due to agranulocytosis