Anitpsychotic Drugs - Segars Flashcards
what are the positive symptoms of schizophrenia?
- hallucinations
- delusions
- disorganized speech/thinking
- agitation
- abnormal motor behavior
which drug class is more commonly utilized as first-line, initial therapy of psychotic disorders?
SGA’s
what is the minimum timeframe necessary to evaluate response to therapy of antipsychotics?
2-3 weeks
- maximum remission benefit may take several months
what do the first generation antipsychotics (FGA’s) primarily block?
dopamine type-2 (D2) post-synaptic receptors
- D2»_space; 5HT
what are the other receptors that FGA’s block?
- muscarinic
- histaminic (H1)
- alpha-adrenergic (a1)
- D2 in nigrostriatal (EPS/movements) and tuberoinfundibular (prolactin) pathways
what are the muscarinic side effects of FGA’s?
- dry mouth
- constipation
- urinary retention
- blurred vision
- sedation
what are the alpha-adrenergic effects of FGA’s?
- orthostatic hypotension
- dizziness/syncope
what is the main histaminic effect of FGA’s?
sedation
what are the two important “other” effects of FGA’s?
risk of QT prolongation and seizure activity
what are the acute extrapyramidal symptoms (EPS)?
- akathisia (restlessness)
- dystonia
- parkinsonism-like movements
when is there a high risk for EPS?
with high D2 occupancy (>78% of receptors occupied)
what are the 2 broad categories of FGA’s?
- low potency (more sedation, hypotension, seizure-threshold reduction)
- high potency (more movement and endocrine effects)
- chlorpromazine
- thioridazine
low potency FGA’s
- fluphenazine
- haloperidol
high potency FGA’s
what are the treatments for EPS? (acute maintenance)
- anticholinergic agents:
- benztropine and trihexyphenidyl - antihistamine agents:
- diphenhydramine
what are the treatments for tardive dyskinesia (TD)
selective vesicular monoamine transporter 2 (VMAT2) inhibitors:
- valbenazine
- deutetrabenazine
what do second generation antipsychotics block along with D2 post-synaptic receptors?
5HT-2A»_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
what are the 4 broad categories of SGA’s?
- 5HT-2A/DA receptor antagonists
- partial DA/5HT-1A receptor agonists
- multi-acting receptor-target agents
- inverse serotonin agonist/antagonist
- iloperidone
- lurasidone
- paliperidone
- risperidone
- ziprasidone
5HT-2A/DA receptor antagonists
- aripiprazole
- brexpiprazole
partial DA/5HT-1A receptor agonists
- asenapine
- clozapine
- olanzapine
- quetiapine
multi-acting receptor-target agents
primavanserin (parkinson’s psychosis)
inverse serotonin agonist/antagonist
what are the common side effects of SGA’s?
- weight gain
- metabolic effects
- stroke -> greater risk in elderly with dementia
- chlopromazine
- fluphenazine
- haloperidol
- thioridazine
FGA’s
- aripiprazole
- cariprazine
- clozapine
- lurasidone
- olanzapine
- quetiapine
- risperidone
- ziprasidone
SGA’s
which FGA’s have the least effect on weight gain and DM?
fluphenazine and haloperidol
which SGA’s have the least effect on weight gain and DM?
ziprasidone (null), aripiprazole (+)
which FGA has the worst effect on weight gain and DM?
chlorpromazine
which SGA’s have the worst effect on weight gain and DM?
- clozapine and olanzapine (++++)
- quetiapine and risperidone (+++)
which FGA’s have the least effect on EPS and TD?
chlorpromazine and thioridazine
which FGA’s have the worst effect on EPS and TD?
fluphenazine and haloperidol
which SGA’s have the least effect on EPS and TD?
clozapine and quetiapine
which SGA’s have the worst effect on EPS and TD?
risperidone
which SGA has the overall least side effects?
aripiprazole
what is the rare-but-severe side effect of clozapine?
agranulocytosis
- monitor WBC, must be enrolled in REMS program
what is the rare-but-severe side effect of olanzapine?
drug reaction with eosinophilia and systemic symptoms (DRESS)
- potentially life threatening drug-induced hypersensitivity reaction
what is Neuroleptic Malignant Syndrome (NMS)?
rare, but potentially fatal, severe Parkinson’s-like movement disorder with wide-spread muscle contraction
what is the tx for NMS?
dantrolene KNOW this muscle relaxer
what baseline labs should be run before beginning antipsychotic medications?
serum glucose, lipids, BMI, blood pressure, waist circumference, family hx of metabolic and CV disease
how can non-adherence to medication be managed?
long acting injectable agents (LAIA’s) every 2-12 weeks depending on agent/dose/patient
what are the 3 LAIA’s Segars want’s us to know?
- risperidone
- olanzapine
- aripiprazole
