anti-psychotics

Question 1

4 DA pathways in brain

Answer 1

nigrostriatal
mesolimbic, mesocortical
tuberoinfundibular

Question 2

nigrostriatal pathway DA effect

Answer 2

normally, DA = coordinated mvmt
too little DA = movement disorders ~PD
drugs that dec DA worsen sx, drugs that inc DA improve sx

Question 3

mesolimbic pathway DA effect

Answer 3

normal DA = social behavior and mood
increased DA = positive SZ sx, mania or psychosis
drugs that dec DA improve sx

Question 4

mesocortical pathway DA effect

Answer 4

normal DA = social behavior and mood

dec DA = negative sx of SZ

Question 5

tuberoinfundibular pathway DA effect

Answer 5

normal DA = prolactin suppression

dec DA = inc prolactin, may cause galactorrhea or irregular menses/ infertility

Question 6

5HT receptors and DA

Answer 6

stimulation 5HT-1A accelerates DA release

stimulation 5HT-2A prevents DA release

Question 7

FDA-approved and off-label uses of antipsychotics

Answer 7

FDA: SZ, bipolar, resistant depression, autism
off: dementia-related agitation/psychosis, OCD, PTSD, Tourette’s, autism

Question 8

MOA first gen antipsychotics (FGA)

Answer 8

D2-blocker in mesolimbic pathway, high occupancy of receptors (90%)
*reduces + but not - sx

Question 9

chlorpromazine

Answer 9

FGA with most anti-ACh effects

ADR: anti-ACH, sedation, orthostasis, EPS

Question 10

fluphenazine

Answer 10

FGA

ADR: EPS

Question 11

perphenazine

Answer 11

FGA

ADR: EPS, some anti-ACh and sedation

Question 12

thioridazine

Answer 12

FGA w inc risk arrhythmia, QT prolongation

ADR: anti-ACh, sedation, orthostasis, EPS

Question 13

thiothixene

Answer 13

FGA

Question 14

haloperidol

Answer 14

FGA with high potency, more ADR (EPS)
available IM/IV
*prototype

Question 15

ADR of FGAs

Answer 15

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

Question 16

extrapyramidal syndromes

Answer 16

movement d/o d/t imbalance of DA and ACh in nigrostriatal pathway (DA inh ACh, when blocked = inc ACh)
tx: anti-ACh (benztropine)

Question 17

acute dystonia

Answer 17

EPS
painful spams and contractions of eye, face, neck, throat muscles
occurs w/i hours of anti-psychotic administration
tx: anti-ACh

Question 18

akathisia

Answer 18

EPS
feeling of restlessness and urge to move
occurs w/i days of anti-psychotic administration
tx: low-dose BZD

Question 19

pseudoparkinsonism

Answer 19

EPS
bradykinesia, rigidity, tremor
occurs w/i weeks of anti-psychotic administration
tx: anti-ACh and reduce AP

Question 20

tardive dyskinesia

Answer 20

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

Question 21

neuroleptic malignant syndrome

Answer 21

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

Question 22

molindone

Answer 22

FGA

ADR: EPS, some anti-ACh, sedation

Question 23

MOA SGAs

Answer 23

“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

Question 24

SGA vs FGA

Answer 24

SGAs have lower EPS, lower prolactin, inc endocrine side effects (glucose intolerance), more expensive

Question 25

clozapine

Answer 25

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

Question 26

risperidone

Answer 26

SGA - relatively cheap

mild ADRs: EPS, sedation, prolactin, QT prolongation, wt gain

Question 27

olanzapine

Answer 27

SGA

ADR: wt gain, higher risk DM and hyperlipidemia, sedation

Question 28

quetiapine

Answer 28

SGA

ADR: abuse potential, sedation, wt gain, some QT prolongation

Question 29

ziprasidone

Answer 29

SGA

ADR: high risk of arrhythmia and QT prolongation

Question 30

aripiprazole

Answer 30

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

Question 31

paliperidone

Answer 31

SGA

not metabolized by CYP450 enzymes

Question 32

asenapine

Answer 32

SGA

ADR: EPS

Question 33

iloperidone

Answer 33

SGA

ADR: QT prolongation, caution w 2D6 and 3A4 inhibitors

Question 34

SGA ADRs

Answer 34

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

Question 35

drug causing agranulocytosis

Answer 35

clozapine

Question 36

drugs causing QT prolongation

Answer 36

ziprasidone, thioridazine, iloperidone

Question 37

drugs causing worst EPS

Answer 37

haloperidol

Question 38

drugs causing severe wt gain and hyperglycemia

Answer 38

clozapine, olanzapine*, quetiapine

Question 39

drugs causing worst akathisia

Answer 39

aripiprazole, asenapine

Question 40

one anti-psychotic not metabolized by CYP450 enzymes

Answer 40

paliperidone