Tp Ii-P3 Exam 3 Schizophrenia

Front 1

Pathophysiology of Schizophrenia
-Structural changes

Back 1

Increased ventriular size
small decreased in brain size
reduced hippocampal volume
reduction in medial temporal lobe volume

Front 2

Pathophysiology of Schizophrenia
Theories

Back 2

1. DA hypothesis (high DA in limbic, low DA in cortical)

2. Glutamatergic dysfunction

3. 5HT abnormalities (Stimulation of 5HT receptor in presynaptic cortical system which causes a decrease in DA release in the striatum.

Front 3

Dopaminergic hypothesis

Back 3

1. Low DA in Mesocortical pathway - cognition, communication

2. High DA in Mesolimbic pathway - Arousal, memory, motivation, behavior, emotion

3. Nigrostriatal pathway - EPS, movement. no changes

4. Tuberoinfundibular pathway - prolactin release. no change

Front 4

Positive sx of schizophrenia

Back 4

Suspiciousness
Unusual thought content (delusions)
Conceptual disorganization
Hallucinations

Front 5

Negative sx of schizophrenia

Back 5

Affective flattening
Alogia (illogical convo)
Anhedonia
Avolition (unmotivated)

Front 6

Cognitive sx of schizophrenia

Back 6

Impaired Attention
Impaired working memory
Impaired executive function

Front 7

Symptoms that are least responsive to tx

Back 7

Delusion
Social skills
Affect
Realistic Planning
Judgment
Insight

Front 8

Haloperidol doses
oral:
IR injection:
Decanoate:

Back 8

Oral: initial 1-15mg/d (QD or divided. Max 100mg/d

IR inj: initial 2-25mg, may give as often as q1h, switch to oral ASAP

Decanoate: initial dose 10-20 times previous TOTAL DAILY oral dose, given q4wks, MUST overlap with oral for ~1month.
-may decrease dose by 25% at 2nd and 3rd month

***Sometimes 5/2 or 10/4 haloperidol & ativan***

Front 9

Haloperidol Decanoate *know*

Back 9

given q 4 wks

Initial dose 10-15 times previous TOTAL DAILY oral dose, given q4wks, MUST overlap with oral for ~1month.

-may decrease dose by 25% at 2nd and 3rd month

Give via A-track

Front 10

Fluphenazine Decanoate *know*

Fluphenazine oral dose

Back 10

Given q 2 wks

Initial: 1.2 times oral dose (rounding to nearest 12.5mg). Overlap with oral for about 1 wk

Give via Z track

Oral dose: 2.5-10mg/d in divided doses at 6-8 hr intervals. mtx dose: 1-5m/d. Some pts may need up to 40mg/d for sx control.

Front 11

SEs for Haliperidol

Back 11

EPS, QTc prolongation

Psychotic sx can improve within 1 wk. widely used in the hospital setting.

Front 12

SGA receptor comparison with FGAs

Back 12

Less D2 affinity, with EXCEPTION OF ARIPIPRAZOLE --> also a partial D2 agonist.

SGAs have 5-HT2A antagonism in cortical system.

Front 13

Risperidone (Risperdal) doses
oral
ODT
Long acting IM

Back 13

Oral: 2mg/d in 1-2 divided doses. Max 8mg
Risperdal M-Tab: ODT
Long acting IM (risperdal Consta) initial 25mg q2wks. Max dose: 50mg q2wks.

Front 14

Long acting IM (risperdal Consta) *Know*

Back 14

Initial 25mg q2wks. Max dose: 50mg q2wks.

Oral should be admin with initial inj. and continued for 3 wks. (must give at least 2 injs b4 d/c oral)

When switching from depot to short-acting formulation, admin short-acting agent in place of the next-regularly scheduled depot inj.

Front 15

Risperidone (Risperdal)

Back 15

2mg/d. Max 8mg/d
(Oral, ODT, IM)

Inj overlap with oral for 3 wks
Less risk for lipid changes

SE: Hyperprolactinemia, EPS (dose-related)

Dose adj w/RENAL & HEPATIC impairement

**Paroxetine increases conc.
**Carbamezapine decreases conc.

Front 16

Olanzapine (Xyprexa)

Back 16

5-10mg QD. Max 20mg/d
(PO, IM short acting for acute agitation, IM long acting for schiz)

NO dosage adj for renal imp.

Metabolic: wt gain, hyperglycemia, inc. in lipids
Anticholinergic
Sedation

**smoking increases conc

Front 17

SGAs with Metabolic SEs

Back 17

Olanzapine, Clozapine, Quietiapine

Front 18

Quetiapine (Seroquel)

Back 18

25mg BID. Max 800mg/d
(IR tab, ER tab)

Sedation, Metabolic SEs (Less than Olanzapine), Cataracts in animal studies

Front 19

Among SGAs, which one binds to D2 weakest? strongest?

Back 19

Weakest = Quetiapine

Strongest = Risperidone (Risperdal)

Front 20

Ziprasidone (Geodon)

Back 20

20mg BID. Max 200mg/d. WITH FOOD
(oral, IM for acute agitation)

NO dose adj for hepatic & renal imp.

QTc prolongation. HIGHEST

Front 21

HIGHEST incidence of QTc prolongation among SGAs

Back 21

Ziprasidone (Geodon)

Front 22

Aripiprazole (Abilify)

Back 22

Partial D2 agonist!

10-15mg QD. Max 30mg/d
(oral, IM for acute agitation)

No dose adj for renal & hepatic imp.
Less wt gain compared to other SGAs

Akathesia, vomiting (11%)!

Front 23

SGAs that's useful for obese pts or pts with metabolic disorders.

Back 23

Aripiprazole (Abilify)

Front 24

Paliperidone (Invega)

Back 24

Oral: 6mg QD. Max 12mg/d
long acting IM (Sustenna): No overlap needed

NO dose adj for Hepatic imp.
Need dose adj for renal

*Adv: can be given +/- 7d
**OROs solution

Front 25

Asenapine (Saphris)

Back 25

5mg SL BID

NO food or drink for 10mins after admin

Sedation, Akathisia

Front 26

Iloperidone (Fanapt)

Back 26

1mg QD. Max 24mg/d

No dose adj in Renal imp.

***decrease Iloperidone dose by 50%!***

1. Strong CYP 2D6 inhibitors (Paroxetine, Fluoxetine)
2. Strong CYP3A4 inhibitors (ketoconazole, clarithromycin)
3. Pts who are poor metabolizers of CYP2D6.

Front 27

Lurasidone (Latuda)

Back 27

40mg QD. max 160mg/d. WITH FOOD.

Akathisia, Hyperglycemia, EPS

Concomitant CYP3A4 inhibitors/inducers:

Moderate CYP3A4 inhibitors: NTE 80mg/d

**CI with strong CYP3A4 inhibitors or Inducer***
i.e Ketozonazole, Rifampin

Front 28

Ketozonazole
Rifampin CI with which SGA?

Back 28

Lurasidone (Latuda). WITH FOOD

Front 29

Clozapine (Clozaril)

Back 29

For tx resistant pts; to reduce risk of recurrent suicidal behavior

12.5mg QD/BID. max 900mg

BBWs: Agranulocytosis*** Need strict monitoring of WBC (>3500) and ANC(>2000)

myocarditis, orthostatic hypotension, seizures, dementia

Front 30

Agranulocytosis defined as?

Back 30

Absolute neutrophil ct (ANC) of <500mm3

Front 31

Must look for what before starting Clozapine? Why? *KNOW**

Back 31

WBC >3500
ANC > 2000

B/c BBW for AGRANULOCYTOSIS

Front 32

SEs of Clozapine

Back 32

Sialorrhea, wt gain, sedation.

**Least likely to cause Tardive Dyskinesia**

Front 33

BBW for all antipsychotics

Back 33

Elderly pts with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo!

Front 34

Pseudoparkinsonism (EPS)

- Agents with highest risk (4)
- Tx

Back 34

EPS: Haloperidol, Risperidol (high dose), Paliperidone, Lurasidone

Tx: Benztropine 1-2mg BID, Diphenhydramine 25-50mg TID, Amantadine (controversial)

Sx resolution in 3-4 days. 2 weeks for a full response

Front 35

S/Sx of EPS

Back 35

Bradykinesia
Tremor (pill-rolling)
Cog-wheel rigidity
Postural instability (shuffling gait, stooped posture)

Onset 1-2 wks

Front 36

s/sx of Dystonias

Back 36

Severe muscle spasm
can be life-threating (pharyngeal-laryngeal dystonia)
Torticollis, oculogyric crisis, opisthotonus, blepharospasm, glossospasm

Onset within 24-96 hrs. (Painful and acute)

Front 37

Dystonias tx

-high risk pts

Back 37

Benztropine 2mg IM/IV
Diphenhydramine 50mg IM/IV
Lorazepam 1-2mg IM

*may repeat in 15mins if unresolved.

*young men, high potency FGAs, and high doses*

Front 38

s/sx of Akathisia

Back 38

Inability to sit still
inner restlessness

*diagnosed with subjective and objective findings*

****Anticholinergic agents NOT effective *** KNOW

Front 39

Tx of Akathisia

Back 39

Propanolol (up to 160mg QD)
Benzodiazepines- controversial in substance abuse

*lower dose or switch medication to lower risk agent*

Front 40

SGAs with highest risk of Akathisia (3)

Back 40

1. Aripiprazole (Abilify)
2. Asenapine (Saphris)
3. Lurasidone (Latuda)

Front 41

s/sx of Tardive Dyskinesia

Back 41

abnormal involuntary movements (orofacial movements, lip smacking, lateral jaw movements, quick, jery extremity movements)

usually occuring late in onset to start of therapy (>6months)

Front 42

TX of Tardive Dyskinesia

Back 42

Vit E may prevent deterioration
Clozapine has been used in moderate to severe cases

Front 43

Least likely to cause Tardive Dyskinesia

Back 43

Clozapine (Clozapil)

Front 44

What are the metabolic complications ***KNOW***

Back 44

Requires at least 3 of the following:

1. Waist circumference (M> 40, F>34in)
2. Fasting TG > 150mg/dl
3. Fasting HDL ( M<40, F<50)
4. BP > 130/85 mmHg
5. Fasting BG > 100mg/dl

Front 45

ADA guide for monitoring parameters SGA

Back 45

Personal/Fhx and Waist circumference @ baseline & annually

FLP @ baseline & 12 wks

weight (BMI) @ baseline, 4 wks, 8 wks, 12 wks, quarterly

BP and FBG @ baseline, every 12wks, & annually

Front 46

ADA guide for monitoring parameters BEFORE starting SGA

Back 46

Personal/family hx, Weight (BMI), waist circumference, BP, FPG, FLP

Front 47

Highest risk of seizures (2)

Lowest risk of Seizure (3)

Back 47

HIGHEST: Clozaril, Chlorpromazine

LOWEST: Risperidone, haloperidol, fluphenazine

Front 48

Sedation & cognition

Back 48

FGA: chlorpromazine, thoridazine, mesoridazine

SGA: Olanzapine, Quietiapine, Clozapine

Front 49

Cardinal Sx of NMS

Back 49

Body temp > 100.4

Altered mental status

Autonomic dysfxn (diaphoresis, labile BP, tachy, tachypnea, or urinary/fecal incontinence

Muscle rigidity

Lab values are nonspecific
***Leukocytosis ( WBC >15,000), CK > 300** KNOW

Front 50

tx of NMS

Back 50

DISCONTINUE medication

IV fluids

Bromocriptine (reverse DA blockade, reduces rigidity, fever, or CK

Dantrolene (SKM relaxant, temp, HR, RR, and CK)

**early recognition and tx is critical**

Front 51

APA tx of choice for persistent suicidal ideation
hostility or aggressive behavior

Back 51

Clozapine

Front 52

History of prolactin elevation avoid?

Back 52

Risperidone

Front 53

Ht of wt gain, hyperglycemia, or hyperlipidemia use?

Back 53

Ziprasidone or Aripiprazole