anti-psychotics Flashcards
4 DA pathways in brain
nigrostriatal
mesolimbic, mesocortical
tuberoinfundibular
nigrostriatal pathway DA effect
normally, DA = coordinated mvmt
too little DA = movement disorders ~PD
drugs that dec DA worsen sx, drugs that inc DA improve sx
mesolimbic pathway DA effect
normal DA = social behavior and mood
increased DA = positive SZ sx, mania or psychosis
drugs that dec DA improve sx
mesocortical pathway DA effect
normal DA = social behavior and mood
dec DA = negative sx of SZ
tuberoinfundibular pathway DA effect
normal DA = prolactin suppression
dec DA = inc prolactin, may cause galactorrhea or irregular menses/ infertility
5HT receptors and DA
stimulation 5HT-1A accelerates DA release
stimulation 5HT-2A prevents DA release
FDA-approved and off-label uses of antipsychotics
FDA: SZ, bipolar, resistant depression, autism
off: dementia-related agitation/psychosis, OCD, PTSD, Tourette’s, autism
MOA first gen antipsychotics (FGA)
D2-blocker in mesolimbic pathway, high occupancy of receptors (90%)
*reduces + but not - sx
chlorpromazine
FGA with most anti-ACh effects
ADR: anti-ACH, sedation, orthostasis, EPS
fluphenazine
FGA
ADR: EPS
perphenazine
FGA
ADR: EPS, some anti-ACh and sedation
thioridazine
FGA w inc risk arrhythmia, QT prolongation
ADR: anti-ACh, sedation, orthostasis, EPS
thiothixene
FGA
haloperidol
FGA with high potency, more ADR (EPS)
available IM/IV
*prototype
ADR of FGAs
also blocks D2 elsewhere -> - sx, mvmt d/o, inc prolactin
anti-ACh, anti-histamine (weight gain), a1-blockade, lower seizure threshold, extrapyramidal sx, tardive dyskinesia (long-term), neuroleptic malignant syndrome
extrapyramidal syndromes
movement d/o d/t imbalance of DA and ACh in nigrostriatal pathway (DA inh ACh, when blocked = inc ACh)
tx: anti-ACh (benztropine)
acute dystonia
EPS
painful spams and contractions of eye, face, neck, throat muscles
occurs w/i hours of anti-psychotic administration
tx: anti-ACh
akathisia
EPS
feeling of restlessness and urge to move
occurs w/i days of anti-psychotic administration
tx: low-dose BZD
pseudoparkinsonism
EPS
bradykinesia, rigidity, tremor
occurs w/i weeks of anti-psychotic administration
tx: anti-ACh and reduce AP
tardive dyskinesia
EPS - irreversible consequence of long-term typical AP use
involuntary abnormal mvmt of face, limbs, neck, trunk
risk inc w age, is reversible in some cases
occurs 6m-1y of AP use
? DA-R supersensitivity
neuroleptic malignant syndrome
rare, potentially fatal
fever, rigidity, altered consciousness, elevated CK
*stop AP and give DA agonist and mm relaxant (dantrolene), BB for HTN and arrhythmia
ADR of FGA and SGA, inc risk if also on lithium or dehydrated
molindone
FGA
ADR: EPS, some anti-ACh, sedation
MOA SGAs
“atypical” because D2a-blockers (lower occupancy) but also block 5HT-2a > D2a in MC and NS pathways (dec risk movement d/o and prolactin inc)
*some are 5HT-1a partial agonists
effective for + and - sx of SZ
SGA vs FGA
SGAs have lower EPS, lower prolactin, inc endocrine side effects (glucose intolerance), more expensive
clozapine
SGA prototype w most ADRs
hepatic metabolism (1A2, 2D6), for tx-resistant SZ
ADR: somnolence, dizziness, hypoTN, wt gain, DM/lipids
severe ADR: agranulocytosis, myocarditis, seizures, inc mortality in elderly w dementia
risperidone
SGA - relatively cheap
mild ADRs: EPS, sedation, prolactin, QT prolongation, wt gain
olanzapine
SGA
ADR: wt gain, higher risk DM and hyperlipidemia, sedation
quetiapine
SGA
ADR: abuse potential, sedation, wt gain, some QT prolongation
ziprasidone
SGA
ADR: high risk of arrhythmia and QT prolongation
aripiprazole
SGA
partial D2 and 5HT1a agonist properties = fewer ADRs
ADR: akithisia, n/v, dizzy, insomnia, sedation, wt gain, DM
BBW: inc mortality in elderly w dementia, inc risk suicide for depressed pts
paliperidone
SGA
not metabolized by CYP450 enzymes
asenapine
SGA
ADR: EPS
iloperidone
SGA
ADR: QT prolongation, caution w 2D6 and 3A4 inhibitors
SGA ADRs
endocrine (d/t 5HT2a block): hyperglycemia, DM, hyperlipidemia, wt gain
EPS less common d/t 5HT2a block
risk of tardive dyskinesia similar to FGA in elderly
QT prolongation
drug causing agranulocytosis
clozapine
drugs causing QT prolongation
ziprasidone, thioridazine, iloperidone
drugs causing worst EPS
haloperidol
drugs causing severe wt gain and hyperglycemia
clozapine, olanzapine*, quetiapine
drugs causing worst akathisia
aripiprazole, asenapine
one anti-psychotic not metabolized by CYP450 enzymes
paliperidone
