Clozapine - 2 Flashcards
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
Cons of lithium augmentation in clozapine therapy
Reports of toxicity, hence, used with caution.
can Lithium augmentation be used in clozapine-induced agranulocytosis
Literature advise against that.
are white cell increased by lithium mature?
yes, mature and functional ( no left shit: immature outpouring from marrow)
mechanisms behind lithium effect on while cell counts
- Granulocyte-Macrophage Colony-stimulating factor (GM-CSF)
- demargination
what is demargination?
The process by which neutrophils are released from the endothelium of blood vessels back into circulation
Availabe forms of clozapine
CLozaril (more commonly used in clinic)
Zaponex
Denzapine
General monitory for clozapine
weekly for first 18 weeks
then fortnightly for 52 weeks
then montly for duration of the treatment
What is CPMS?
Clozaril Patient Monitoring Service, anyone wishing to dispense clozaril need to be registred with CPMS
who makes a colour for clozpine blood level?
CPMS
what does an amber colour mean?
Patient must take another test in one or two days, and twice weekly subsequently until resutl is normalized.
what does an red colour mean?
patient should stop clozaril
what service is used for zaponex?
Zaponex Treatment Access System (ZTAS)
what service is used for Denzapine?
Denzapine Patient Monitoring System (DPMS)
10% of patients on clozapine develop what side effects?
Drowsiness & insomnia
Constipation & nausea and vomitting
Salivation
Weight Gain
Dizziness
Dyspepsia
prevalence of sialorrhoea in clozapine therapy?
31%
when is hypersalivation worse?
Early in treatment course
At evening
RCT based evidenced Rx for hypersalivation?
Hyoscine Hydrobromide
Amisulpride
troubles with hypersalivation?
socially embarrassing
potentially life-threatening (asphyxiation)
Antagonist mechanism of clozapine
-D1, D2, D3 and D4
-Alpha 1 & 2
-M1, M2, M3, M5
- H1
-5-HT 2C
agnonist mechanism of clozapine
M4
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
