031315 antipsychotics Flashcards
dopamine hypothesis
schizophrenia results from hyperactivity of dopaminergic neurons or their receptors, particularly those w terminals in limbic areas of brain
all antipsychotics interact w
dopamine systems
dopaminergic pathways
mesolimbic tract (dopamine hyperactivity leads to positive symptoms)
mesocortical tract (diminished dopaminergic activity leads to negative symptoms)
nigrostriatal pathway (dopamine blockade here results in increased extrapyramidal symptoms. blockade of 5HT2a results in decreased extrapyramidal symptoms)
tuberoinfundibular tract (dopamine blockade increases prolactin release)
newer antipsychotics block
serotonin 5HT2 receptors in forebrain and striatum in addition to dopamine, so EPS decreased
have greater potency with 5HT2 than w dopamine receptors
chlorpromazine
little potency (less affinity for dopamine D2 receptor)
in addition to dopamine receptors, what to typical antipsychotics bind to?
block histamine, muscarinic receptors (thus the side effects)
actions of antipsychotic drugs
decrease in psychotic behavior
sedation
extrapyramidal effects (dystonias, Parkinsonism, akathisia, tardive dyskinesia)
early vs late EPS side effects of antipsychotics
early: acute dystonia, parkinsonism, akathisia
late: tardive dyskinesia
newer atypicals have decreased
risk of extrapyramidal symptoms
other than EPS, what other side effects do antipsychotics have
anticholinergic
orthostatic hypotension (blockade of alpha receptors)
neuroendocrine effects (result of DA receptor blockade, causing increased prolactin)
allergic and idiosyncratic effects: liver, blood, cutaneous (esp newer drugs)
cardiac effects: thioridazine
decreased seizure threshold (esp phenothiazines)
weight gain, diabetes (more in atypicals-esp olanzapine, risperidone, clozapine, quetiapine)
neuroleptic malignant syndrome
potentially lethal hypodopaminergic side effct of antipsychotic drugs
hyperthermia, Parkinson-like symptoms, mutism, possible death
tx includes cooling and hydration, bromocriptine (DA agonist) and dantrolene (sk musc relaxer b/c musc rigidity is causing body temp to rise)
typical antipsychotics
phenothiazines
thioxanthine derivatives
butyrophenone derivative
pimozide
thioxanthine derivatives
pharm is similar to phenothiazines
butyrophenone derivatives
pharmacologically similar to high potency piperazine derivatives
pimozide’s use
antipsychotic
tx of Tourette’s (used when haloperidol doesn’t work)
advantages of atypical antipsychotics over typicals
- lower risk of EPS (better compliance)
- poossible lower incidence of tardive dyskinesia
- improve negative symptoms perhaps
- improve positive symptoms in many antipsychotic-resistant pts
- perhaps less impact on cognitive functioning
- perhaps more cost effective
clozapine’s MOA
blocks D4 and 5HT2 receptors
muscarinic antagonist
improves neg symptoms
side effects of clozapine
lowers seizure threshold more than other antipsychotics
fatal agranulocytosis
so it’s used when other drugs don’t work
olanzapine’s MOA
5HT2 antagonist
D1 and D2 antagonist, some D4
side effects of olanzapine
weight gain, diabetes olanzapine abuse (b/c of sedating effects)
intramuscular depot preps of atypical antipsychotics
risperidone
paliperidone
quetiapine
similar to risperidone and olanzapine in effects on schizophrenia symptoms and side effects
shorter half life drug
quetiapine (good for elderly)
use of quetiapine
antipsychotic
augmentation in depression
aripiprazole MOA
partial D2 agonist and 5HT2 antagonist
use of aripiprazole
adjunct in depression
antipsychotic
uses of antipsychotic drugs
acute psychotic episodes
chronic schizophrenia
manic episodes, bipolar disorder (aripiprazole, olanzapine, quetiapine, ziprasidone, rispierdone, asenapine, lurasidone)
schizoaffective disorder (paliperidone)
augmentation in depression (aripiprazole, olanzapine, quetiapine)
Tourette’s-haloperidol, pimozide
antiemesis-not thioridazine
