Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

8. Psychopharmacology > Antipsychotics Part II (includes Clozapine) > Flashcards

Antipsychotics Part II (includes Clozapine) Flashcards

1
Q

how might you describe clozapine as an antipsychotic

A

“last line”

low potency

highly anticholinergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the risk of EPS with clozapine

A

very low incidence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the major metabolite of clozapine

A

norclozapine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the affinity of clozapine for the D2 receptor

A

second lowest (quetiapine is lowest)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what antipsychotic is indicated in parkinsons dissease psychosis/dementia psychosis

A

clozapine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

compared to placebo, what is the risk of EPS with clozapine

A

risk of EPS with clozapine is same as placebo

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

there are only two psychotropic medications that have been shown clinically to reduce the risk of suicide–what are they

A

clozapine

lithium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is the starting dose of clozapine

A

25-50mg po daily OR 12.5 mg qHS or BID

can be titrated 25-50mg per day up to 300mg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how do you titrate clozapine (doses)`

A

25-50mg po daily, increasing by 25-50mg daily until 300mg

then after 300mg, titration should not exceed more than 25mg each day

once at daily doses of 400, 500, 600, 700 etc… should maintain at each interval for AT LEAST TWO WEEKS before moving on

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how should you titrate clozapine if going above doses of 500mg

A

consider increasing the dose by 25-50mg ONLY every two weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is the maximum dose of clozapine

A

900mg (canadian guidelines say 600mg)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is considered an adequate trial of clozapine

A

minimum 8 weeks

preferably 12 weeks

(reaching a minimum dose of 400mg per day)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what two formulations are available for clozapine

A

oral or liquid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what physical exams should be done before starting clozapine

A

height
weight
waist circumference
BP
HR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what lab work should be ordered before starting clozapine

A

CBC + differential

fasting glucose

AST, ALP, ALT

lipid panel

HbA1c

CRP

Lytes and Cr

high sensitivity troponin I

baseline ECG

b-HCG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

in which populations do clozapine plasma levels tend to be LOWER compared to plasma levels in others at a similar dose

A

plasma levels tend to be lower in:

younger patients

males

smokers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

in what population does clozapine plasma levels tend to be HIGHER compared to others on a similar dose

A

plasma levels tend to be higher in:

asians

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

when should you take the blood sample to most accurately assess clozapine plasma level

A

either right before morning dose or 10-12 hours post-dose if only one dose taken per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is the mechanism of action of clozapine

A

loosely blocks dopamine D2 receptors–> reduces positive symptoms of psychosis and stabilizes affective symptoms

blocks serotonin 5HT-2A receptors–> enhancement of dopamine release in certain brain regions and thus reducing motor side effects–> possibly improves cognitive and affective symptoms

also interacts with H1, M1, alpha-1 receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what receptors does clozapine interact with

A

D2
5HT-2A
M1
H1
alpha-1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

list 4 indications for clozapine use

A

treatment resistant schizophrenia (HC/FDA approved)

reduction in risk of recurrent suicidal behaviour in patients with schizophrenia or schizoaffective disorder (FDA approved)

treatment resistance bipolar disorder

tardive dyskinesia (practical indication)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how long does it take to see the effect of clozapine

A

some people respond within one week

recommended to wait at least 4-6 weeks but not considered resistant until adequate trial of 12 weeks long

some patients require up to 16-20 weeks to show good response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

after what dose of clozapine should doses be divided

A

above 300mg should be divided

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

after how many missed doses of clozapine do you need to restart at a lower dose

A

after 2 missed days need to re-initiate at lower dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

if its been less than 48 hours since last clozapine dose, what do you do for the next dose?

A

resume previous dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

if its been 48-72 hours since last clozapine dose, what do you do for the next dose?

A

re-initiate at starting/lower dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

if its been 72 hours or more since last clozapine dose, what do you do for the next dose?

A

re-titrate from starting dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Stahl’s suggests that asian patients need what % of the dose of clozapine compared to caucasian patients

A

about HALF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

how often should you do vitals when initiating clozapine

A

at least daily, including orthostatic vitals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

how often do you need to do CBC+ diff (ANC) when on clozapine

A

weekly x 6 months

then q2weeks x 6 months

then q4 weeks INDEFINITELY

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

how often do you need to do CRP + troponin when on clozapine

A

weekly x first 4 weeks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

how often do you need to do fasting glucose and lipids when on clozapine

A

q3-6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

how often do you need to do ECG when on clozapine

A

at least one once reach steady state + if any clinical indication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

how often do you need to do clozapine + norclozapine levels when on clozapine

A

once target dose reached

consider when patient unwell/has infection or starts or stops smoking

target ratio above 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what other psychotropic medication can improve clozapine:norclozapine ratio

A

fluvoxamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

why do we care about the clozapine: norclozapine ratio

A

?better efficacy and decreased side effects

norclozapine is thought to be more responsible for side effects like sedation etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what are target clozapine levels

A

350-600ng/mL
= 1070-1800nmol/L

some patients may need levels above 600ng/mL for adequate response

some sources indicate levels up to 1000ng/mL are not unsafe and should be pursued in non-responders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

above what clozapine level does risk of adverse drug reactions increase

A

1000ng/mL (= 3100nmol/L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

what is the expected metabolic ratio of clozapine: norclozapine in a nonsmoking male

A

1.32

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

what dose of clozapine would you expect to need to reach a clozapine level of 350ng/mL in a:

female smoker

A

435mg/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what dose of clozapine would you expect to need to reach a clozapine level of 350ng/mL in a:

female non smoker

A

265mg/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

what dose of clozapine would you expect to need to reach a clozapine level of 350ng/mL in a:

male smoker

A

525mg/day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what dose of clozapine would you expect to need to reach a clozapine level of 350ng/mL in a:

male nonsmoker

A

325mg/day

*basically, you need higher doses of clozapine if they’re male, and if they’re a smoker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

why might looking at the metabolic ratio between clozapine and norclozapine be helpful

A

to understand presence of an inducer or an inhibitor

if ratio is low (ie more norclozapine than expected) then there is probably an inducer present or they are a CYP 1A2 ultra rapid metabolizer

if the ratio is high (i.e less norclozapine than expected) but not too high (i.e between 1.7-3.0) then likely presence of weak inhibitor or they are CYP poor metabolizers

if ratio is very high (i.e above 3) then there is likely presence of a strong inhibitor or viral or bacterial illness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

list 9 common side effects of clozapine

A

sedation (usually transient)

dizziness

hypotension

hypersalivation (or dry mouth)

tachycardia

constipation (can be lethal)

metabolic effects

sexual dysfunction

nocturnal enuresis (21% risk)

(also nausea, GERD, transaminitis, fever)

46
Q

what change in HR can be expected with clozapine

A

increase of 10-20 bpm

47
Q

what is the average weight gain associated with clozapine

A

5-8kg on average

1/5 will gain 10% of body weight

about 60-75% of people will gain weight

48
Q

like 5 rare but serious possible side effects of clozapine

A

agranulocytosis (/neutropenia)

myocarditis

seizures

NMS

EPS

49
Q

what is the risk of agranulocytosis with clozapine

A

about 1% risk

50
Q

what is the risk of myocarditis with clozapine

A

1-5% risk in some studies

?overestimate

51
Q

what is the risk of seizures with clozapine

A

5% risk at 500mg/day dose

52
Q

describe how a clozapine overdose would present

A

arrhythmias

excess salivation

respiratory depression

altered state of consciousness

MAY BE LETHAL

53
Q

first line treatment for clozapine induced sialorrhea

A

orally applied anticholinergics (so as not to increase constipation risk)

ATROPINE 1% drops

ipratropium 0.6% spray (under tongue)

can consider low dose terazosin before glycopyrrolate if oral applied meds dont wory

54
Q

why is clozapine more constipating than other antipsychotics

A

because strong anticholinergic, antihistaminic and anti 5HT3

55
Q

what is the mean colon transit time for food/feces in someone on clozapine compared to normal

A

normal = 23 h

on clozapine = 105 h

56
Q

how to manage constipation associated with clozapine

A

minimize other anticholinergics

encourage exercise, hydration, dietary fiber (20g)

stool softeners like docusate and osmotic/stimulant laxatives

*avoid bulk forming laxatives

57
Q

how much does the risk of seizures with clozapine increase when you go from doses below 300mg to above 600mg

A

below 300mg = 1% risk

300-600mg = 2.7% risk

above 600mg = 4.4 % risk

*EEG abnormalities without seizures are common

58
Q

how do you manage seizures with clozapine

A

reduce dose of clozapine

anti-epileptic medications

59
Q

what % of cases of myocarditis on clozapine occur in the first month

A

about 88% (average is 17days)

60
Q

how might myocarditis related to clozapine present

A

“flu like” symptoms

fever

tachy (if they’re not tachy, they dont have myocarditis–> but may have tachy without myocarditis)

chest pain (50%)

SOB (35%)

61
Q

what lab findings would you expect in myocarditis

A

elevated ESR/CRP

elevated CK

elevated BNP

elevated troponin

62
Q

what is the gold standard for diagnosis of myocarditis

A

echo and cardiac MRI

63
Q

what is the sensitivity and specificity of elevated troponin for myocarditis

A

sensitivity 83%

specificity 91%

64
Q

under what conditions should you stop clozapine if myocarditis is suspected

A

if CRP is above 100

if troponin is 2x upper limit of normal

65
Q

how do you manage clozapine related myocarditis after diagnosis

A

stop clozapine

do serial troponins, ECG and echo

follow up ECG in 2-4 weeks then q6months

66
Q

what is “agranulocytosis”

A

absence of granulocytes–> neutro-, eosino- and basophils

67
Q

what is “benign ethnic neutropenia”

A

individuals of african heritage may have lower baseline neutrophils

can consult heme (then call company line and have monitoring parameters adjusted)

68
Q

what are the “green” “yellow” and “red” parameters for clozapine based on

A

neutrophil and WBC count

are monitoring for possible agranulocytosis

69
Q

what is the WBC level associated with “green” status for clozapine monitoring

A

WBC above 3.5 x 10^9/L

70
Q

what is the neutrophil level associated with “green” status for clozapine monitoring

A

neutrophils above 2

71
Q

what action should be taken if someone falls in the “green” zone for clozapine monitoring

A

continue clozapine and continue current frequency of blood test

72
Q

what is the WBC level associated with “yellow” status for clozapine monitoring

A

WBC below 3.5

73
Q

what is the neutrophil level associated with “yellow” status for clozapine monitoring

A

neutrophils below 2

74
Q

what do you do if someone falls in the “yellow” zone of clozapine monitoring

A

continue clozapine

monitor CBC at least TWICE WEEKLY until back to green

75
Q

what is the “flashing yellow” zone of clozapine monitoring

A

yellow drop–> basically a downward trend but not yet out of green zone officially

WBC less than 4 with WBC fall of 3x10^9/L in the last four weeks

OR

neutrophils less than 2.5 with neutrophil fall of 1.5 in the last four weeks

76
Q

what should you do if someone falls in the “flashing yellow” zone of clozapine monitoring

A

continue clozapine

monitor CBC at least twice weekly unitl back to green

77
Q

what is the WBC level associated with “red” status for clozapine monitoring

A

WBC below 2

78
Q

what is the neutrophil level associated with “red” status for clozapine monitoring

A

neutrophils below 1.5

79
Q

what should you do if someone falls in the “red” zone on clozapine monitoring

A

stop clozapine

monitor daily for vitals and signs of infection

repeat CBC in 24 hours to confirm low neutrophils

if remains confirmed, d/c clozapine

admit to ER if patient has symptoms of infection

80
Q

what will happen if a patient falls into the yellow zone on clozapine monitoring

A

lab will call patient

if patient has fever, they go to hospital

81
Q

what enzyme if responsible for the major metabolism of clozapine

A

CYP 1A2

82
Q

what other CYP enzymes are involved in clozapine metabolism apart from CYP 1A2

A

3A4

2D6

2C19

83
Q

what other psychiatric medication should be used cautiously with clozapine

A

fluvoxamine

it is a 1A2 inhibitor

84
Q

why does cigarette smoke decrease clozapine levels

A

it is a CYP 1A2 inducer

85
Q

like four common medications that are CYP 1A2 inhibitors (and thus increase clozapine levels)

A

fluvoxamine

caffeine

ciprofloxacin

oral contraceptivecs

86
Q

list 3 common meds/substances that are CYP1A2 inducers (and thus decrease clozapine levels)

A

smoking

carbamazepine

omeprazole

87
Q

list 9 contraindications to clozapine treatment

A

hypersensitivity to clozapine

myeloproliferative disorder

uncontrolled epilepsy

hx agranulocytosis or severe granulocytopenia

CNS depression

paralytic ileus

acute liver disease (with nausea, jaundice, anorexia) or progressive liver failuer

unable to undergo blood tests

severe cardiac disease (this is a relative contraindication)

88
Q

what is the bioavailability of clozapine? is it affected by food?

A

27-50%

not affected by food

89
Q

what is the time to peak concentration of clozapine

A

2.5 h

(range is 1-6 h)

90
Q

does clozapine undergo first pass metabolism

A

yes–> significant in the gut and liver

91
Q

what is the half life of clozapine

A

12h (range is 4-66h)

92
Q

can you use clozapine in cases of renal or liver failure

A

must use with caution

93
Q

what is the response rate for people with schizophrenia with:
1. clozapine

  1. high dose olanzapine
  2. other antipsychotics
A
  1. clozapine = above 40%
    (30% after 3 mo and 60% if maintained)
  2. high dose olanzapine = 0-7%
  3. other = less than 5%
94
Q

what should you be aware of and monitoring for is discontinuing clozapine

A
  1. rebound psychosis
    –may occur unless very slowly tapered
    –taper by 100mg/week or slower
  2. cholinergic rebound
    –occur in 1-4 days
    –N/V, diarrhea, sweating, urinary urgency, anxiety, delirium
    –tx with anticholinergics (i.e benztropine)
95
Q

how does the TRIPP working group recommend approaching clozapine refectory schizophrenia

A

for positive sx–> raise clozapine level above 350ng/mL–>
consider addition of 2nd antipsychotic (best evidence–though sparse–for ABILIFY PO, or amisulpride)
–>or ECT

for negative sx–> consider addition of antidepressant i.e citalopram (not specifically investigated)

can also augment with CBT and psychosocial interventions

96
Q

has safety/efficacy been established for clozapine in kids

A

no–> preliminary research suggests efficacy for early-onset treatment resistant schizophrenia

97
Q

what risk category is clozapine for pregnancy/lactation

A

risk level B

(animal studies do not show adverse effects but no controlled studies in humans)

98
Q

what is “morning pseudoneutropenia”

A

a physiologic pronounced diurnal variation in circulating neutrophils some people have

if WBC low in AM, repeat in PM before changing clozapine treatment

99
Q

what blood parameters are considered “critical” for clozapine monitoring? what do you do in this case?

A

WBC below 1

neutrophils below 0.5

place patient in protective isolation with close observation

physician must watch for signs of infection

100
Q

do you have to restart monitoring regimen if more than 3 days of clozapine are missed

A

yes–> its basically starting the whole thing over

101
Q

how long do clozapine induced fevers usually last

A

2-3 days in first month of treatment

*make sure to rule out NMS or myocarditis

102
Q

list 3 antipsychotics that have “no effect” on QTc

A

brexpiprazole

cariprazine

lurasidone

103
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

aripiprazole

A

low

104
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

risperidone

A

moderate-high

105
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:
quetiapine

A

moderate

106
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

olanzapine

A

moderate

107
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

loxapine

A

low

108
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

clozapine

A

low

109
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

haloperidol

A

moderate

110
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

asenapine

A

low

111
Q

state whether the following antipsychotic has low, moderate or high effect on QTc prolongation:

paliperidone

A

moderate

8. Psychopharmacology (21 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions