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MRCPSYCH_Paper B_MENTOR & More_Dr. ART > Clozapine - 1 > Flashcards

Clozapine - 1 Flashcards

1
Q

when was clozapine first made?

A

1950’s

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2
Q

the europian journey of clozapine?

A

Introduced in 1970’s
withdrawn despite affecitveness in 1976
Reintroduced in 1990 with mandatory blood monitoringg

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3
Q

cause of withdrawal of clozpaine in europe in 1976?

A

some death due to agranulocytosis

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4
Q

Indication for clozpane in schizo?

A

treatment-resistant schizophrenia

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5
Q

how is treatment-resistant schizophrenia (TRS) defined?

A

Ongoing symptoms and functional impairments despite two adequate trials of different antipsychotics with proper adherence.

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6
Q

% of TRS?

A

20-33%

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7
Q

% of TRS responding to clozapine?

A

a whopping 60%

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8
Q

what are those who don’t respond to even clozapine called?

A

Ultra Resistant ( no response to trial of 2 antipsychotic and clozapine)

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9
Q

% of schizophrenia that will be ultra Resistant?

A

12-20%

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10
Q

how long should you wait after clozapine administration to monitor blood level?

A

12 hours ideally

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11
Q

how many days should patients be on clozapine before monitoring is performed and why?

A

7 days
to achieve a steady state

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12
Q

what is average clozapine dose in the UK

A

450 mg / day
- - -

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13
Q

in what range of clozapine dose is response seen?

A

150-900 mg / day

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14
Q

what threshold most studies have suggested for clozapine?

A

0.34-0.42 mg/l

(can be as high as .5 mg/l)

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15
Q

is there an established threshold for clozapine?

A

No!!!!

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16
Q

what does a threshould above 0.5 mg/l mean?

A

-should be treated with caution
-there is a risk of @@@Seizure@@@

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17
Q

what patients might need lower dose?

A

non-smokers
elderly
females
patients on SSRs (enzyme inhibitors)

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18
Q

can inflammations affect clozapine level?

A

Yes, it increased.

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19
Q

what does Maudsley 14th edition say if the clozapine plasma level is < 0.35?

A

if poor response, increase.
if good response, maintain.

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20
Q

what does Maudsley 14th edition say if the clozapine plasma level is 0.35-0.5?

A

if good response, maintain
If poor, increase to >0.5 mg/l and consider prophylactic anticonvulsants

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20
Q

what does Maudsley 14th edition say if the clozapine plasma level is < 0.5-1 mg/l?

A

*if there is a poor response, consider prophylactic anticonvulsant and consider augmentation.
if that is poorly tolerated, reduce the dose if augmentation worked.
*If good response and well tolerated, just consider prophylactic anticonvulsant and maintain the dose.
*If good response and poorly tolerated, consider prophylactic, reduce the dose ( if there is no history of poor response in low doses)

21
Q

so when clozapine is between 0.5 to 1 mg/l, additing what agent must be considered?

A

prophylactic anticonulsant

21
Q

what does Maudsley 14th edition say if the clozapine plasma level is < 1mg/l?

A

*if poor response, attempt augmentation and add anticonvulsant, then reduce the dose ( to >1 mg/l)…Consider abandoning clozapine
*If there is a good response but poorly tolerated, add anticonvulsant and slowly reduce the dose
*If there is good response and well tolerated, add anticonvulsant and monitor closely…only attempt dose reduction if toleration declined

22
Q

when should clozapine abandoning be considered?

A

if blood level is above 1 mg/l and there is poor response to current dose and reduction.

23
Q

what is the name of major metabolite of clozapine

A

Nor clozapine (norclozapine)

24
Q

how is norclozapine different than clozapine?

A

Longer half life
Factuate less
Can be used to indicate recent compliance

25
Q

the average ratio of clozapine and norclozapine?

A

1.3

26
Q

can clozapine and norclozapine ratio be used for?

A

to assess compliance and enzyme induction

27
Q

what clozapine norclozpine ratio range means good compliance and no

A

0.5-2.5

28
Q

what can >2.5 clozpaine norclozpine ratio mean?

A

either
-the blood is taken less than 11 hours after last administration or
-metabolism of clozapine is saturated or
-or enzyme inhitors are added
-or patient has stopped smoking

29
Q

what does it mean if the clozapine norclozapine ratio is <.5

A

either
- blood is taken after 13 hours of last administration
- poor compliance
- enzyme induction ( smoking or rifampicin)

30
Q

Green code in clozapine monitoring for blood cells?

A

WBC > 3.5
Neutrophil >2

31
Q

Amber code in clozapine monitoring for blood cells

A

WBC 3.0 - 3.5
Neutrophil 1.5-2

32
Q

Red code in clozapine monitoring for blood cells

A

WBC < 3
Neutrophil < 1.5

33
Q

How is neutropenia is defined?

A

absolute neutrophil count of less than 1.5 * 10^9/L

34
Q

prevalence of neutropenia in clozpine takers?

A

2.7%

35
Q

Onset of Neutropenia in clozapine therapy?

A

half of 2.7% in the first 18 weeks and 3 quarter in first year.

36
Q

RISK factor for neutropenia

A

younger age
Afro-Caribbean 77%
Low baseline WBC count

37
Q

Is risk for neutropenia in clozapine therapy dose dependent?

A

Nope!

38
Q

Neutropenia dose dependent?

A

No!!!

39
Q

How is agranulocytosis defined?

A

Absolute neutrophil count of less than .5 * 10^9/L

40
Q

Prevalence of agranulocytosis in clozapine therapy?

A

0.8%

41
Q

is agranulocytosis fatal if not treated

A

yes

42
Q

death rate in those who develop agranulocytosis?

A

3%

43
Q

why can’t clozapine used with drugs like carbamazepine?

A

both have risk of agranulocytosis

44
Q

Risk for agranulocytosis?

A

Older age
Asians (2.4 times more than Caucasians)

45
Q

age risk difference between neutropenia and agranulocytosis

A

neutropenia risk decreases with age
agranulocytosis risk increases with age

46
Q

racial risk difference between neutropenia and agranulocytosis

A

neutropenia more in afro-Caribbeans (77% more risk)
agranulocytosis more in Asians ( 2.4 times more than Caucasians)

47
Q

Rechallenge blood dyscrasia prevalence

A

one third of those who stop clozapine due to neutropenia or agranul.

48
Q

how is blood dyscrasia on rechallence descriped?

A

Rapid onset
More severe
Last longer

MRCPSYCH_Paper B_MENTOR & More_Dr. ART (69 decks)

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