Clozapine - 2 Flashcards by Arteen Ahmed

Pros of lithium augmentation in clozapine therapy?

Enable patients to continue on clozapine when they develop neutropenia as lithium can raise the white cell counts

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Cons of lithium augmentation in clozapine therapy

Reports of toxicity, hence, used with caution.

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can Lithium augmentation be used in clozapine-induced agranulocytosis

Literature advise against that.

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are white cell increased by lithium mature?

yes, mature and functional ( no left shit: immature outpouring from marrow)

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mechanisms behind lithium effect on while cell counts

Granulocyte-Macrophage Colony-stimulating factor (GM-CSF)
demargination

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what is demargination?

The process by which neutrophils are released from the endothelium of blood vessels back into circulation

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Availabe forms of clozapine

CLozaril (more commonly used in clinic)
Zaponex
Denzapine

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General monitory for clozapine

weekly for first 18 weeks
then fortnightly for 52 weeks
then montly for duration of the treatment

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What is CPMS?

Clozaril Patient Monitoring Service, anyone wishing to dispense clozaril need to be registred with CPMS

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who makes a colour for clozpine blood level?

CPMS

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what does an amber colour mean?

Patient must take another test in one or two days, and twice weekly subsequently until resutl is normalized.

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what does an red colour mean?

patient should stop clozaril

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what service is used for zaponex?

Zaponex Treatment Access System (ZTAS)

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what service is used for Denzapine?

Denzapine Patient Monitoring System (DPMS)

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10% of patients on clozapine develop what side effects?

Drowsiness & insomnia
Constipation & nausea and vomitting
Salivation
Weight Gain
Dizziness
Dyspepsia

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prevalence of sialorrhoea in clozapine therapy?

31%

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when is hypersalivation worse?

Early in treatment course
At evening

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RCT based evidenced Rx for hypersalivation?

Hyoscine Hydrobromide

Amisulpride

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troubles with hypersalivation?

socially embarrassing
potentially life-threatening (asphyxiation)

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Antagonist mechanism of clozapine

-D1, D2, D3 and D4
-Alpha 1 & 2
-M1, M2, M3, M5
- H1
-5-HT 2C

agnonist mechanism of clozapine

paradox of hypersalivation in clozapine anticholinergic effects

parasympathetic stimulation causes high salivary flow
sympathetic stimulation causes high levels of protein

What are causes behind the hypersalivation paradox?

M4 agonist
while the M antagonist diminishes saliva, the alpha 2 antagonist increases salivation
reduced frequency of swallowing

Adverse Event associated with Clozapine

Agranulocytosis
Myocarditis, pericarditis and cardiomyopathy
Seizures
Severe orthostatic hypotension w/ or w/out syncome
Colitis
Pancreatitis
Thrombocytopenia (low platelets)
Insuline resistance and diabetes

prevalence of diabetes over 10 years in clozapine therapy

33% 33% 33% 33%

BNF advices caution in what circumstances for clozpaine therapy?

BPH Susceptibility to angle-closure glaucoma over 60s

When is the risk of seizure high in clozpaine therapy?

high dose 500 mg/day or plasma level >0.5 mg/L

what to do when seizure risk is high in clozapine therapy?

Consider add prophylactic anticonvulsants

candidate prophylactic anticonvulsants in clozpaine therapy?

Topiramate Lamotrigine Gabapentin Valproate

what if seizure happened in clozpaine therapy?

stop clozapine for one day restart at half the previous dose add anticonvulsant

Prevalence of myocarditis in clozapine therapy?

1 in 500 to 1 in 1000 ( generally 1 in 500)

onset of myocarditis in clozapine therapy

80% in 4 weeks 90% in 8 weeks

pathological findings of myocarditis in clozapine therapy?

damaged myocytes and eosinophilic infiltration

what do eosinophilic infiltration indicate in clozpaine induced myocarditis?

type 1 Ig E-mediated acute hypersensitivity reaction

Does a mild increase in inflammatory markers and eosinophil at the start of clozapine therapy mean absolute progression to myocarditis?

Nope!

sign and symptoms of clozapine-induced myocarditis?

Fever Chest pain Tachycardia Dyspnoea Flu-like symptoms Elevated oesinophils Elevated cardiac biomarkers.

Cardiac biomarkers for clozapine induced myocarditis?

Treponin Creatine kinase

which one is superior, troponin or CK?

Troponin

Mortality in clozapine induced myocarditis

50%

How treatment resistant schizophrenia (TRS) is defined?

Blood level Adequate duration

How duration of clozpine therapy helps in defining TRS?

30% respond in 6 weeks 20% by 3 months 20% by 6 months

How blood level helps in determining TRS?

It has to reach .35-.45 mg/l before saying there is resistant (check enzyme inhibitors too)

Best antipsychotics to use for augmentation in clozapine therapy?

amisulpride and sulpride

why amisulpride and sulpride are thought to be best for clozapine augmentation?

their d2 affinity which complement clozapine's affinity for other receptors and lacks that.

best mood stabilizer for clozapine augmentation?

lamotrigine

what antipsychotics should be avoided in clozapine augmentation?

Olanzapine Sertinole Pimozide

other availabe antipsychotics for augmentation in clozapine therapy/

Risperidone Aripirazole Ziprasidone Omega-3-triglycerides Topiramate and lamotrigi

If clozapine failed to work, or patient refused, then what?

High dose of olanzapine High dose of Olanzapine with memantine High dose of Olanzapine with allopurinol Max dose amisulpride (1200 mg/day) Max dose of aripiprazole (aroo30) D-alanine and D-Serin ECT