Antipsychotics pharm Flashcards
1st generation agents
-ChlorpromAZINE
-FluphenAZINE
-Haloperidol
-ThioridAZINE
-Thiothixene
(CFHTT)- azines
2nd generation agents
-AriPIPRAZOLE
-ClozAPINE
-OlanzAPINE
-QuetiAPINE
-RisperIDONE
-ZiprasIDONE
(ACOQRZ)- prazole, apine, idone
main diff b/w 1st and 2nd generation agents
-reduction in movement-disorder SE’s in 2nd gen!!
Schizophrenia hypotheses
Dopamine hypothesis
- direct/indirect DA-agonists provoke psychotic rxns in non-schizophrenics and exacerbate sx’s in schizophrenics
- alterations in DA-mediated transmission in schizophrenics- inc DA occupancy of D2 R
Dopamine Pathways relevant to schizophrenia sx’s
- mesolimbic- + sx’s
- mesocortical- neg and cognitive sx’s
Mesolimbic pathway
- VTA to NA
- motivation, emotions, reward, + sx’s of schizophrenia
- D2 antagonists reduce + sx’s of schizophrenia!!! (hallucinations, delusions, disorganized speech/thinking, agitation, abnormal motor behavior)
mesocortical pathway
- VTA to PFC (cortex)
- cognitive and negative sx’s (apathy, avolition, alogia, cognitive deficits, social withdrawal)
Dopamine Pathway relevant to SE’s
- Nigrostriatal- EPS and TD
- tuberoinfundibular- hyperprolactinemia
Nigrostriatal pathway
- substantia nigra to striatum
- purposeful movement
- D2 antagonism induces extrapyramidal sx’s
Tuberoinfundibular pathway
- hypothalamus to infundibular region
- dopamine inhibits prolactin release!!!
- D2 antagonism inc PRL levels
1st gen antipsychotics- primarily do what?
(CFHTT- azines)
-block D2 post-synaptic R’s!!!- D2»_space; 5HT2!!!!!!
FGA’s also block what?
other R’s- causing SE’s!!!
- muscarinic
- alpha-adrenergic
- histamine
- QTc prolongation and seizures
muscarinic effects
(anti-cholinergic)
- dry mouth
- constipation
- urinary retention
- blurred vision
- sedation
alpha-adrenergic effects
- orthostatic hypotension
- dizziness/syncope
histamine effects
-sedation
1st gen SE’s- dopamine effects
- hyperprolactinemia- tuberoinfundibular pathway
- EPS (extrapyramidal sx’s)/ TD (tardive dyskinesia)- nigrostriatal pathway
Extrapyramidal sx’s- tx
(anticholinergic agents)
- diphenhydramine
- benztropine
- trihexyphenidyl
1st gen- high EPS risk assoc with what?
-high D2 occupancy= high EPS risk
FGA’s- 2 categories
- low potency- sedation, hypotension, seizure-threshold reduction- Chlorpromazine, Thioridazine
- high potency- EPS and prolactin effects- Fluphenazine, Haloperidol, Thiothixene
2nd Gen antipsychotics- block what?
- block D2 post-synaptic R’s
- block 5HT2A
- stronger 5HT2A R blockers than D2 R blockers!!!!
2nd Gen antipsychotics- dual 5HT2A/D2 theory
- 5HT2A antagonism inc DA transmission in nigrostriatal pathway- improved neg and cognitive sx’s via inc DA release in PFC
- reduced EP SE’s
SGA’s- additional info
- rapidly dissociate from D2 R’s- reduced EP SE’s
- D2 partial agonists- aripiprazole
- 5HT1A full agonist (ziprasidone) and partial agonists (Aripiprazole, clozapine)
SGA’s- SE’s?
Common: -weight gain -hyperglycemia, hyperlipidemia Rare: -QTc prolongation/ECG changes -Stroke
wt gain, diabetes, hypercholesterolemia- more common in?
-2nd gen!!!
EPS/TD, PRL elevation- more common in?
-1st gen!!!
Wt gain and diabetes- 1st gen
-Chlorpromazine!!
Wt gain and diabetes- 2nd gen
-no- aripiprazole, ziprasidone
-yes- clozapine, olanzapine
(more common in 2nd gen!!!)
Hypercholesterolemia- 1st gen
-Chlorpromazine!!!
Hypercholesterolemia- 2nd gen
- no- aripiprazole, ziprasidone
- yes- Clozapine, Olanzapine
EPS/TD- 1st gen
- all!!
- less- Chlorpromazine, Thioridazine
EPS/TD- 2nd gen
-yes- Risperidone
PRL elevation- 1st gen
-all!!
PRL elevation- 2nd gen
-Risperidone!!
Sedation- 1st gen
-Chlorpromazine, Thioridazine
Sedation- 2nd gen
-Clozapine, olanzapine, quetiapine
Anticholinergic SE’s- 1st gen
-chlorpromazine, thioridazine
Anticholinergic SE’s- 2nd gen
-yes- Clozapine
Orthostatic hypotension- 1st gen
-chlorpromazine, thioridazine
Orthostatic hypotension- 2nd gen
clozapine
QTc prolongation- 1st gen
-Thioridazine
QTc prolongation- 2nd gen
-Ziprasidone
2nd gen- rare but severe SE’s
- agranulocytosis- clozapine- monitor WBC, REMS program!!!!
- DRESS (drug rxn w eosinophilia and systemic sx’s)- olanzapine
- Neuroleptic malignant syndrome (parkinson’s-like movement disorder w wide-spread m contraction)
Neuroleptic malignant syndrome- tx
-dantrolene!!- closes ryanodine R (Ca does not go in)
Antipsychotic monitoring
Baseline:
- serum glucose
- fasting lipid profile
- weight (BMI)
- BP
- waist circumference
- personal/family hx of metabolic and CV dz
more commonly used as 1st line?
-atypical agents!! (2nd gen)
Tx of psychotic disorders- LAIAS
(long-acting injectable agents)- used for non-adherence!!!
- 1st gen- Haloperidol decanoate, Fluphenazine decanoate
- 2nd gen- Risperidone, Olanzapine, Aripiprazole lauroxil, paliperidone palmitate (ROAP)
Tx of psychotic disorders- therapeutic pearls
-2-3 wks necessary to evaluate response to tx (maximum benefit- several months)
multi-drug resistant- tx?
-clozapine
psychotic w anti-suicidal thoughts/behaviors- tx?
-clozapine
