Antipsychotics

Question 1

Of the four dopamine tracks, which is responsible for psychosis?

Answer 1

Mesolimbic

Question 2

Which neurotransmitter is thought to play a role in psychosis?

Answer 2

Dopamine (increased levels lead to psychosis)

Question 3

How does dopamine binding affinity affect the clinical anti-psychotic effects?

Answer 3

D2 receptor antagonist binding affinity strongly correlates with anti-psychotic effects. This supports the evidence that dopamine mediates psychosis

You can also convert meds based off dosing equivalents

Question 4

Name the prototype/original phenothiazine/FGA

Answer 4

Chlorpromazine

Question 5

List the side effects/relative prevalence of side effects associated with FGA’s and dopamine binding

Answer 5

extra-pyramidal symptoms, increased prolactin, sexual dysfunction, infertility, decreased bone density…

Fairly common

Question 6

List the side effects/relative prevalence of side effects associated with FGA’s and muscarinic binding

Answer 6

Anticholinergic –> blurred vision, urinary retention, dry mouth, constipation

Very common

Question 7

List the side effects/relative prevalence associated with FGA’s and adrenergic receptor binding

Answer 7

Increased orthostasis, increased risk of falls

Very common

Question 8

List the side effects/relative prevalence associated with FGA’s and Histamine receptor binding

Answer 8

Sedation, weight gain

Very common

Question 9

Name the three most important high potency FGAs

Answer 9

Haloperidol
Fluphenazine
Trifluoperazine

Question 10

What is the advantage of high potency FGAs over low potency FGAs in terms of side effects? Disadvantages?

Answer 10

High potency FGAs bind primarily to dopamine receptors, which means there are no appreciable muscarinic/adrenergic/histamine receptor side effects.

Disadvantages: increased extra-pyramidal symptoms

Question 11

What percentage of patients on high potency antipsychotics develop tardive dyskinesia?

Answer 11

20-50%

Question 12

List a few of the classic tardive dyskinesia movements

Answer 12

lower facial and tongue movements- blinking, chewing grimacing, lip puckering/smacking,

These movements are permanent

Question 13

Dopamine antagonism in the tuberoinfundibular tract leads to which side effects?

Answer 13

Increased prolactin
Galactorrhea, lactation, gynecomastia
Decreased GnRH –> decreased LH and FSH –> irregular menstruation and infertility
*Osteopenia –> increased risk of fractures

Question 14

What side effect differentiates FGAs from SGAs?

Answer 14

extrapyramidal- SGAs do not have extrapyramidal side effects.

Question 15

Second generation antipsychotics block which two receptors?

Answer 15

Dopamine

Presynaptic serotonin 5HT

Question 16

Generally speaking, which class of antipsychotics cause more weight gain vs less weight gain?

Answer 16

More: -apines

Less- idones

Question 17

Describe the partial agonist properties of aripiprazole in low and high dopamine environments

Answer 17

Low: acts as an agonist
High: acts as an antagonist

Question 18

How do the partial agonist properties of aripiprazole stabilize the dopamine-serotonin stabilization?

Answer 18

Keeps >65% activated, but less than 80% activated..

Gets enough agonism for benefit without activating side effecfts

Question 19

When is clozapine indicated?

Answer 19

3rd line treatment - for use after failure of 2 other antipsychotics

Question 20

Describe the benefits of clozaprine

Answer 20

Greater efficiency with overall psychopathology in patients non-responsive to psychotherapy

Greater efficacy in treatment of negative symptoms of schizophrenia

Lowers risk of suicide in patients with a history of attempted suicide

Question 21

What are the potential negative side effects that make clozapine a 3rd line treatment option?

Answer 21

Very sedating, weight gain, metabolic syndrome, anti-cholinergic

Rare, serious: Agranulocytosis, myocarditis and lowered seizure threshold

Question 22

Neuroleptic malignant syndrome is a rare side effect of what class of drugs?

Answer 22

First generation antipsychotics

Question 23

What are the symptoms of neuroleptic malignant syndrome?

Answer 23

Mental status change
Rigidity: increased CPK and tremor
Fever: > 40 common
Dysautonomia: increased HR, changes in BP, increased RR and hypoxia

Question 24

Sudden death is a side effect of FGAs and SGAs in what patient population?

Answer 24

elderly patients with dementia w/ psychosis

Question 25

What is the half life of most of the SGAs? What is the major exception?

Answer 25

20-24 hours.

Aripiprazole is much longer (75 hours)

Question 26

Which drug is the prototype atypical (SGA) antipsychotic?

Answer 26

Clozapine

Question 27

What is the range of dopamine receptors needed to achieve positive effects without inducing all of the negative side effects?

Answer 27

65-80%

Question 28

What is the only treatment for tardive dyskinesia?

Answer 28

Clozapine-

It can help, but not necessarily cure it

Question 29

Why is risperidone always paired with palliperidone when discussing drug pharmacokinetics and pharmacodynamics?

Answer 29

Risperidone is metabolized to palliperidone

Question 30

What is a major difference between risperidone and palliperidone/

Answer 30

Palliperidone is 80% excreted renally- good for use in patients with liver issues

Question 31

Which two SGAs need to be taken with food?

Answer 31

Ziprasidone and Lurasidone