Anitpsychotic Drugs - Segars

Question 1

what are the positive symptoms of schizophrenia?

Answer 1

• hallucinations
• delusions
• disorganized speech/thinking
• agitation
• abnormal motor behavior

Question 2

which drug class is more commonly utilized as first-line, initial therapy of psychotic disorders?

Answer 2

SGA’s

Question 3

what is the minimum timeframe necessary to evaluate response to therapy of antipsychotics?

Answer 3

2-3 weeks

- maximum remission benefit may take several months

Question 4

what do the first generation antipsychotics (FGA’s) primarily block?

Answer 4

dopamine type-2 (D2) post-synaptic receptors

- D2&raquo_space; 5HT

Question 5

what are the other receptors that FGA’s block?

Answer 5

• muscarinic
• histaminic (H1)
• alpha-adrenergic (a1)
• D2 in nigrostriatal (EPS/movements) and tuberoinfundibular (prolactin) pathways

Question 6

what are the muscarinic side effects of FGA’s?

Answer 6

• dry mouth
• constipation
• urinary retention
• blurred vision
• sedation

Question 7

what are the alpha-adrenergic effects of FGA’s?

Answer 7

• orthostatic hypotension

- dizziness/syncope

Question 8

what is the main histaminic effect of FGA’s?

Answer 8

sedation

Question 9

what are the two important “other” effects of FGA’s?

Answer 9

risk of QT prolongation and seizure activity

Question 10

what are the acute extrapyramidal symptoms (EPS)?

Answer 10

• akathisia (restlessness)
• dystonia
• parkinsonism-like movements

Question 11

when is there a high risk for EPS?

Answer 11

with high D2 occupancy (>78% of receptors occupied)

Question 12

what are the 2 broad categories of FGA’s?

Answer 12

1. low potency (more sedation, hypotension, seizure-threshold reduction)
2. high potency (more movement and endocrine effects)

Question 13

• chlorpromazine

- thioridazine

Answer 13

low potency FGA’s

Question 14

• fluphenazine

- haloperidol

Answer 14

high potency FGA’s

Question 15

what are the treatments for EPS? (acute maintenance)

Answer 15

1. anticholinergic agents:
   - benztropine and trihexyphenidyl
2. antihistamine agents:
   - diphenhydramine

Question 16

what are the treatments for tardive dyskinesia (TD)

Answer 16

selective vesicular monoamine transporter 2 (VMAT2) inhibitors:

• valbenazine
• deutetrabenazine

Question 17

what do second generation antipsychotics block along with D2 post-synaptic receptors?

Answer 17

5HT-2A&raquo_space; D2

NOTE: some SGA’s also block other DA receptors (D-1,3,5) and also have greater propensity to be an agonist/antagonist on one or more other 5HT receptors

Question 18

what are the 4 broad categories of SGA’s?

Answer 18

1. 5HT-2A/DA receptor antagonists
2. partial DA/5HT-1A receptor agonists
3. multi-acting receptor-target agents
4. inverse serotonin agonist/antagonist

Question 19

• iloperidone
• lurasidone
• paliperidone
• risperidone
• ziprasidone

Answer 19

5HT-2A/DA receptor antagonists

Question 20

• aripiprazole

- brexpiprazole

Answer 20

partial DA/5HT-1A receptor agonists

Question 21

• asenapine
• clozapine
• olanzapine
• quetiapine

Answer 21

multi-acting receptor-target agents

Question 22

primavanserin (parkinson’s psychosis)

Answer 22

inverse serotonin agonist/antagonist

Question 23

what are the common side effects of SGA’s?

Answer 23

• weight gain
• metabolic effects
• stroke -> greater risk in elderly with dementia

Question 24

• chlopromazine
• fluphenazine
• haloperidol
• thioridazine

Answer 24

FGA’s

Question 25

- aripiprazole - cariprazine - clozapine - lurasidone - olanzapine - quetiapine - risperidone - ziprasidone

Answer 25

SGA's

Question 26

which FGA's have the least effect on weight gain and DM?

Answer 26

fluphenazine and haloperidol

Question 27

which SGA's have the least effect on weight gain and DM?

Answer 27

ziprasidone (null), aripiprazole (+)

Question 28

which FGA has the worst effect on weight gain and DM?

Answer 28

chlorpromazine

Question 29

which SGA's have the worst effect on weight gain and DM?

Answer 29

- clozapine and olanzapine (++++) | - quetiapine and risperidone (+++)

Question 30

which FGA's have the least effect on EPS and TD?

Answer 30

chlorpromazine and thioridazine

Question 31

which FGA's have the worst effect on EPS and TD?

Answer 31

fluphenazine and haloperidol

Question 32

which SGA's have the least effect on EPS and TD?

Answer 32

clozapine and quetiapine

Question 33

which SGA's have the worst effect on EPS and TD?

Answer 33

risperidone

Question 34

which SGA has the overall least side effects?

Answer 34

aripiprazole

Question 35

what is the rare-but-severe side effect of clozapine?

Answer 35

agranulocytosis | - monitor WBC, must be enrolled in REMS program

Question 36

what is the rare-but-severe side effect of olanzapine?

Answer 36

drug reaction with eosinophilia and systemic symptoms (DRESS) - potentially life threatening drug-induced hypersensitivity reaction

Question 37

what is Neuroleptic Malignant Syndrome (NMS)?

Answer 37

rare, but potentially fatal, severe Parkinson's-like movement disorder with wide-spread muscle contraction

Question 38

what is the tx for NMS?

Answer 38

**dantrolene** KNOW this muscle relaxer

Question 39

what baseline labs should be run before beginning antipsychotic medications?

Answer 39

serum glucose, lipids, BMI, blood pressure, waist circumference, family hx of metabolic and CV disease

Question 40

how can non-adherence to medication be managed?

Answer 40

long acting injectable agents (LAIA's) every 2-12 weeks depending on agent/dose/patient

Question 41

what are the 3 LAIA's Segars want's us to know?

Answer 41

- risperidone - olanzapine - aripiprazole