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Therapeutics III > Schizophrenia - Block 3 > Flashcards

Schizophrenia - Block 3 Flashcards

1
Q

What is the dopamine theory of schizo?

A

Overactive dopaminergic system leads to psychosis

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2
Q

What are the dopamine major pathways that affect the brain?

A

Mesolimbic: positive symptoms - delusions, hallucinations, paranoia
Mesocortical: negative symptoms - social withdrawal
Nigrostriatal: EPS affecting movement
Tuberoinfundibular: Controls prolactin secretion

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3
Q

Describe the functions of dopamine excess and absense?

A
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4
Q

What are first gen antipsychotics?

A
  1. Haloperidol
  2. Thioridazine
  3. Chloropramazine
  4. Fluphenazine
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5
Q

What are SGA?

A
  1. Risperidone
  2. Clozapine
  3. Quetiapine
  4. Aripiprazole
  5. Ziprasidone
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6
Q

Differentiate the activity of FGA and SGA?

A

FGA: High potency for D2 antagonism
* Low anti-HAM

SGA: Low potency D2 antagonism
* Seratonin action
* Anti-ham

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7
Q

Differentiate the indication of FGA and SGA?

A

FGA: Better at treating positive sx than negative
SGA: Better at treating negative sx

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8
Q

Differentiate the ADRs of FGA and SGA?

A

FGA: EPS, hyperprolacteminemia, NMS< anticholinergic
SGA: weight gain, T2DM, argranulocytosis, sedation

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9
Q

What is the glutamate theory?

A

Glutamate is responsible for learning, memory, neuronal processing, and brain development
* deficiency -> schizophrenia

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10
Q

Positive sx?

A
  1. Hallucinations
  2. Delusions
  3. Paranoia/suspiciousness
  4. Conceptual disorganization
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11
Q

Negative sx?

A
  1. Blunted/flat affect
  2. Social withdrawal
  3. Lack of personal hygiene
  4. Prolonged time to respond
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12
Q

Cognitive sx?

A
  1. Poor executive function
  2. Impaired attention
  3. Impaired working memory (fail to learn from mistakes)
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13
Q

Drugs that causes schizo?

A
  1. Anticholinergics
  2. Dopamine agonist (requip, mirapex, sinemet)
  3. Dextromethorphan
  4. Systemic steroids
  5. AMphetamines
  6. Bath salts, cocaine, LSD, meth, PCP
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14
Q

Feelings of extreme suspicion, persecution or grandiosity, or a combination of these.

A

Paranoid schizophrenia

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15
Q

Incoherent thoughts, but no delusions?

A

Disorganized schizo

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16
Q

Withdrawal, negative affect and isolation and marked psychomotor disturbances?

A

Catatonic schizo

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17
Q

Delusions or hallucinations may go away, but motivation or interests in life is gone?

A

Residual schizo

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18
Q

Sx of both schizo and major mood disorder such as depression?

A

Schizoaffective disorder

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19
Q

How do you diagnose schizo?

A

DSMV: major sx - ≥2 of the following for at least 1 month (must have one of bolded)
* Delusions
* Hallucinations
* Disorganized speech
* Disorganized/catatonic behavior
* Negative sx

Must affect domains of life for at least 6 months

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20
Q

Describe the phases of schizo?

A

Prodromal: gradual development of sx that may go unnoticed
Acute: full-blown episode of psychotic behavior
Stabilization: Acute sx begin to decrease and phase may last for months
Stable: Declined sx nut nonpsychotic sx (ax and depression) may be present

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21
Q

What is the diagnostic process for identifiying schizo?

A
  1. Physical/lab exams can rule out med condition
  2. Rule out substance induced psychosis
  3. Imaging (CT, MRI, PET)
  4. History and mental status exam (MSE)
  • no reliable biomarkers
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22
Q

What can you initiate for acute?

A
  1. Haloperidol
  2. Olanzipine
  3. Ziprasidone
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23
Q

What do you treat for stable?

A
  1. Pharm and CBT
  2. Adherence check
  3. Remission is rare (decrease s/s)
  4. Assess suicide risk
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24
Q

What are the tx options for schizo?

A
  1. typical AP
  2. Atypical
  3. AP injections
  4. Talking Treatments/Education/Support Groups/CBT
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25
Q

When would you see better outcomes in schizo tx?

A

The quicker we begin tx

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26
Q

How affective are the use of antipsychotics?

A
  1. Sleep disturbances and agitation in the first 2 days
  2. 6-8 weeks for full effects
  3. No sx relief 2-4 weeks use alternative or increase dose
  4. Multiple AP is not effective but increases the risk of side effects
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27
Q

AP BBW?

A

Increased mortality in elderly patients with dementia related psychosis

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28
Q

AP ADRs?

A

Sedation
Hypotension
Extrapyramidal
W eight gain
Anticholinergics
Sexual dysfunction
Metabolic changes
Endocrine (increased prolactin)

DA/5-HT and anti-HAM

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29
Q

Typical AP

Tx, indication, ADR

A

Tx:sx improve in a week with peak effect seen at 6 weeks
Indication: acute psychotic episodes
ADR: EPS, hyperprolactinemia
* Low potency = more anti-HAM (anticholinergic, sedation, orthostatic hypotension, tachycardia)

30
Q

Antihist ADR?

A

sedation and weight gaim

31
Q

Antimuscarinic ADRs?

A

Dry mouth, blurred vision, ED, urinary retention, tachycardia, mydriasus

32
Q

Cardiac ADR of FGA?

A
  1. Orthostatic hypotension -> dz
  2. QT prolongation (thioridazine, IV haloperidol)
33
Q

What is the cause of neuroleptic mlignant syndrome?

A

From FGA due to dopamine blockade

34
Q

What is NMS? How is it treated?

A

Occurs 2 weeks of FGA tx: muscle contraction and rigidity, hyperthermia, tachycardia, death
Tx:
* taper off quickly switch to SGA
* Cool pt off(antipyretic, cooled bed)
* Muscle relation with BDZ, DA agonist (bromocriptine to replace the decreased DA), Dantrolene (muscle relaxant)

35
Q

High potency FGA

A

For acute mania:
1. Haldol (haloperidol)
2. Modecate (fluphenazine)
3. Thiothixene, trifluoperaxene

36
Q

Medium potency FGA?

A
  1. Loxapine
  2. Perphenazine
37
Q

Low potency FGA?

A
  1. Chlorpromazine (Largactil)
  2. Thioridazine (antihis, cv, anticholinergic effects)

Lower sz threshold (except thioridazone)

38
Q

What i anti-ham?

A

Antihistamine- sedation, weight gain
Anti- alpha adrenergic - orthostatic hypotension, cardiac abnormalities, sexual function
Anti-muscarinic – dry mouth, tachycardia,urinary retention , blurry vision, constipation

39
Q

What is acute dystonia?

A

spasmodic or sustained muscle spasm

40
Q

What is akathisia?

A

severe motor restlessness

41
Q

What is pseudoparkinsonism?

A

Bradykinesia, mask-like face, resting tremor

42
Q

What is tardive dyskinesia?

A

Mouth movements (lip smacking, puckering, tongue profusion)

43
Q

Tx for akathisia?

A
  1. Lowering AP dose
  2. BZD
  3. Anticholinergics (Benadryl, benztropine)
  4. Centrally acting b-blocker (propranalol)
44
Q

Tx for dystonia?

A
  1. Benztropine or Benadryl
  2. Prophylaxis/tx
45
Q

Tx pseudo parkinsonism?

A
  1. anticholinergic agents such as benztropineordiphenhydramine
  2. Propranolol (if tremor is the main sx)
46
Q

Tx for tardive dyskinesia?

A
  1. May be irreversible even after the offending AP is DC
  2. Stop drug switch to SGA with low EPS risk (quetiapine, clozapine)
  3. Valbenazine(ingrezza); deutetrabenazine
47
Q

Types of EPS ADRs?

A
  1. Acute dystonia
  2. Tardive dyskinesia
  3. Akathisia
  4. Pseudoparkinsonism
48
Q

Haloperidol

Dosing, Indication

A

Dosing: long term inj (deconate IM Q4W)
* 0.5-2mg BID-TID, up to 30mg per day
* PO to IM multiply by 10-20 times the PO dose

Indication: acute and chronic psychosis, Tourettes

49
Q

What is considered first line for Schizo?

A

SGA

50
Q

ADRs of SGA?

A
  1. Metabolic SE (weight gain, diabetes, hypercholesterolemia) - clozapine, quetiapine, olanzapine
  2. Hyperprolactimenia (risperidone, paliperidone)
  3. Dose related EPS (risperidone, lurasidone, paliperidone)
  4. QT prolongation (zi[rasidone)
  5. CV events (risperidone, olanzapine, aripiprazole)
  6. SZ (clozapine-dose dependent)
51
Q

WHat SGA has a lower risk for EPS?

A

Quetiapine

52
Q

What are the monitoring parameters for SGA?

A
  1. Metabolic SE (weight, lipis, BP, BG)
  2. Smoking can reduce olanzapine and clozapine
  3. Agranulocytosis (stop therpy ANC <1000 cells/mm^3)
53
Q

What SGA has the greatest risk for MS and agranulocytosis?

A

Clozapine

54
Q

What are the requirements for Clozarril National Registry?

A
  1. Baseline ANC of 1500
  2. Dosing depends on blood levels
  3. Verify the patient is enrolled in the single shared Clozapine REMS Program
  4. Verify the prescriber is certified in the single shared Clozapine REMS Program
  5. Obtain a “Predispense Authorization” each time from the Clozapine REMS Program
  6. Verify the ANC is acceptable or verify the prescriber hasauthorized continuing treatment if the ANC is abnormal
55
Q

Significant ADRs associated with Clozapine?

A
  1. SZ
  2. Sedation
  3. Myocarditis
  4. Weight gain
  5. Constipation
  6. Respiratory se
  7. Dementia
56
Q

With all the BBW, why is clozapine even used?

A

More effective in the tx of refractory schizo and in reducing suicidality

57
Q

How do we manage clozapine SE?

A
  1. Caution in titration
  2. WBC counts
  3. Acceptable counts are WBC’s > 3000 and ANC’s > 1500
  4. Initial symptoms of agranulocytosis are fever, sore throat, cold/flu symptoms or sores that do not heal
  5. Anticonvulsants to control sz
58
Q

How often do we do WBC counts for clozaine?

A
  1. Baseline prior to admin
  2. Weekly for first 6 months
  3. Biweekly for 6 months
  4. Monthly after
59
Q

How does aripriprazole differ from SGA?

Dosing form, MOA, ADR, Indication

A

FOrm: tab, ODT, IM, suspension
MOA: partial agonist at D2 and 5-HT1A, antagonist at 5-HT2A
ADR: Akathisia, ax, insomnia, less weight gain
INdicaion: irritability with autism and Tourettes, useful in depression

60
Q

Ziprozidone

Counseling, ADR

A

Geodon
Counseling: take with food to increase absorption
ADR: QT prolongation and CV illness
* Avoid commitant use with anti-arrhythmtics

61
Q

SGA general ADRs?

A
62
Q

Long acting formulations to improve adherence?

A

Haldol decanoate (once q4 weeks)
Risperdal costa( once q 2 weeks)
Invega sustenna(once q4 weeks)
Invega trinza (once q 3months)
Abilify maintena(once q 4 weeks)
Abilify-Aristadagiven q 4-8 weeks depending on dose

63
Q

ODT formulations to prevent cheeking?

A

Clozapine, olanzapine,risperidone, aripiprazole, asenapine

64
Q

Acute IM formulations to relief acute agitation?

A

Haldol cocktail(haloperidol,lorazepam, diphenhydramine)
DO NOT mix olanzapine with BDZ due to risk of orthostasis

65
Q

Whenpicking an SGA for a patient I consider?

A
  1. Hx
  2. ADR profile of SGA
  3. Patient adherence
  4. Cost
66
Q

How long is a SGA drug trial?

A

4-6 weeks upt to 8 weeks

67
Q

Pimavanserin

Indication, MOA, ADR

A

Indication: psychosis in PD
MOA: Seratonin agonist, antagonist
ADR: QT prolongation, avoid in drugs that prolong QT, peripheral edema, confusion

68
Q

What is schzo tx resistance?

A
  1. ≥30% is a success
  2. improvement can usually be seen after two weeks of a therapeutic dose, if not we are probably not going to see it at week 8
  3. Failure to respond to 2 AP trials
69
Q

RF for tx resistance?

A
  1. check for adherence -35% are not when plasma levels are checked
  2. increased metabolism- fast metabolizers/ DDI at CYP2D6 and CYP3A4
  3. Substance use disorder
  4. Severe stress
  5. Smokers
  6. Korean
  7. Check if patient reached appropriate plasma levels
  8. Check if patient had reached appropriate dose
70
Q

How do you manage tx resistance?

A
  1. Increasign dose is not beneficial -> switch to alt
  2. Switch AP with different MOA
  3. Combo tx
  4. Adjunct: add therapy that treats specific to sx (BZD for agitation, AD for depression)
  5. ACEI, B-blockers, Carbamazepine, Lithium, Valproate, Memantine

Therapeutics III (40 decks)

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