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College Royal Takser > clozapine > Flashcards

clozapine Flashcards

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1
Q

6 indications de clozapine à part schizophrénie résistante

A

manie résistante (add)
psychose chez parkinson
agressivité
suicidalité
polydipsie psychogène
dyskinésie tardive

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2
Q

traitement de non réponse a la clozapine

A

verifier adhérence

verifier niveaux plasmatiques et augmenter la dose (seuil minimal 350 ng/ml, aller ad 1000 ng/ml si toléré)

ajouter un AP avec D2 effect

ajouter ECT

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3
Q

work up avant debuter clozapine

A

signes vitaux

BMI

constipation? smoking? seizures?

labs: FSC (neutro, eosino), E+/creat/liver/HbA1C/lipids

ECG (QT)

abd XR if needed

insciption au programme de suivi de clozapine

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4
Q

QT correction error: how to estimate the true QT at rate >72/sec

A

current formula (Bazett) overestimates QT

Fridericia formula QTc=QT/racine cube du RR

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5
Q

titration clozapine inpatient smoker/non smoker

A

titration pour smoker (non smoker - 50%)

se rendre à 200 en 1 sem et 400 en 2 sem

25-50-100-150-200

ensuite par increment de 50 mg (par 2-3 jours) ad 400

dosage clozapine 7 jours apres 400mg

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6
Q

titration clozapine pour outpatient smoker/non smoker

A

doses pour smoker (non smoker - 50% de la dose)

ad 100 jour6

ad 200 jour12

ad 300 jour18

ad 400 jour24

dosage plasmatique 7 jours apres 300mg

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7
Q

à quel delais d’attendre de la myocardite?

A

1-7 weeks after initiation of Tx, most cases - within 4 weeks

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8
Q

monitoring after initiaion of clozapine

A

within 3 months - possible side effects

then - FSC

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9
Q

8 side effects of clozapine

A

neutropenia

constipation - ileus

sedation

orthostasis - tachycardia

sialorrhea

seizure

metabolic syndrome

DRESS syndrome

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10
Q

constipating medications - psychotrops

A

chlorpromazine +++

olanzapine

quetiapine >600

TCA

antiparkinsonian: cogentin, diphenhydramine

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11
Q

constipating medications - non psychotrops

A

opiods

iron

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12
Q

managing cholinergic rebound

A

si possible, baisser la dose par 100 mg die ad 100mg die

ensuite - par increments de 25 mg q 4-7 jours

if sleep disturbance - 25-50 mg benadryl HS

if abrupt d/c - strart cogentin (benztropine) at equivalent dose (50 mg clozapine in nonsmoker = 1 mg cogentin = 25 mg benadryl) for at least 2 weeks

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13
Q

options pour pts parkinson sous clozapine si d/c

A

pimavanserin (nuplazid) - a first-in-class atypical antipsychotic that does not induce clinically significant antagonism of dopaminergic, adrenergic, histaminergic, or muscarinic receptors. It is the first FDA-approved drug indicated for the treatment of the hallucinations and delusions in PD-associated psychosis

possibly - quetiapine

ECT

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14
Q

options pour pts parkinson sous clozapine si d/c

A

pimavanserin (nuplazid) - a first-in-class atypical antipsychotic that does not induce clinically significant antagonism of dopaminergic, adrenergic, histaminergic, or muscarinic receptors. It is the first FDA-approved drug indicated for the treatment of the hallucinations and delusions in PD-associated psychosis

possibly - quetiapine

ECT

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15
Q

mechanisme d’action - clozapine

A

alpha 1 antagonist

H1 antagonist

M1 et M3 antagonism

norclozapine - agonist M1-M5 exept M3 (donne sialorrhea via agonisme muscarinique)

D2 antagost (low affinity)

5HT2A - inverse agonist

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16
Q

conditions qui affectent le metabolisme de la clozapine (activité CYP 1A2)

A

tabagisme (hydrocarbons, pas la nicotine, CYP 1A2 inducers)

infections (augmentent niveaux de clozapine x3)

caffeine (heavy intake can increase clozapine level)

polymorphisme génétique

17
Q

vrai ou faux: individus avec la neutropénie ethnique bénigne sont plus grand risque de développer la neutropénie sévère

A

faux

18
Q

quand le risque de neutropénie est le plus élévé?

A

6 premiers mois

19
Q

quel est le temps de résolution de la neutropénie après la d/c de la clozapine?

A

12 jours (médiane)

20
Q

seuil neutrophiles pour débuter/continuer clozapine

A

ANC égal ou plus que 2000/mm3

BEN: 1000

21
Q

eosinophiles et clozaril: seuil d’alerte

A

700/mm3

22
Q

qui est à risque de BEN?

A

origine africaine

23
Q

première action si low ANC and no BEN

A

vérifier Rx (épival, ab + bcp autres très courants)

24
Q

US guidelines in case of low ANC under clozapine

A

if more than 1500 - continue

if 1000-1499 - continue

if moderate neutropenia (500-999) - interrupt and consult hematology

if severe neutropenia - d/c Tx and no rechallenge if risks>benefits

25
Q

vrai ou faux: lithium peux être utilisé comme prévention de neutropénie

A

oui, à doses autour de 300 HS

26
Q

clozapine induced constripation management

A

avoid opioids, iron and other cholinergic drugs

start PEG (level 1) and docusate (no evidence) and stimulant (bisacodyl - moderate evidence) at the beginning of Tx

do not use psyllium - exacerbates constipation

27
Q

vrai ou faux: mortalité d’ileus dépasse celle de neutropénie chez pts sous clozapine

A

vrai

ileus - 15-27%

neutropenie - 2.2-4.2%

28
Q

clozapine: how to manage sedation?

A

reduce dose if high

adjunct aripiprazole or modafinil (if other methods failed - data weak)

29
Q

vrai ou faux: sedation is the cause no1 of clozarilTx discontinuation by pts

A

vrai

30
Q

Clozaril: management of orthostasis

A

fluid and salt intake

slowing titration

manage alpha 1 antagonists and antihypertensive drugs

last method - fludrocortisone

31
Q

Clozaril: management of tachycardia

A

rule out orthostasis

rule out other causes

atenolol

32
Q

Clozaril: management of sialorrhea

A

atropine drops 1% (1st line)

botulinum toxin-B (2nd line)

amilsulpride or clonidine

avoid anticholinergic - risk of ileus

33
Q

Clozapine: management of seizures

A

Do NOT stop clozapine

Valproate - the most studied and recommended (risk of neutropenia/thrombocytemia/hyperNH3)

manage as epilepsy

34
Q

Clozapine: management of metabolic effects

A

all patients are candidates for metformin (weight gain early)

monitor BMI/lipid profile/Hb1Ac

35
Q

Clozapine: rate and onset of fever, myocarditis, interstitial nephritis, DRESS, cardiomyopathy

A

Fever - in 20%, within first 8 wks

Myocarditis - up to 3% within the first 6-8 wks

Intestitial nephritis, serosostis and DRESS - less common, within first 60 days

Cardiomyopathy - many months after

36
Q

Clozapine: rate of incontinence and enuresis and their management

A

up to 40% early in Tx

20% - persistent

manage other antipsychotics

do not use anticholinergic

37
Q

vrai ou faux: si clozapine donne élevation des enzymes hépatiques il faut d/c

A

faux

élevation x2 du baseline est normale chez 30%

38
Q

clozapine: rate and management of thrombocytopenia

A

3%

no action needed unless less than 50K - risk of bleeding - d/c

39
Q
A

College Royal Takser (10 decks)

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