Clozapine - 3 Flashcards
what class is clozapine classfied in ?
tricyclic benzodiazepine drivatives
mechanism of clozpaine
—-antagonists at D1, D2, D3 and D4
—-antagonists at alpha adrenoceptors 1 and 2
—-antagonists at 5-HT2A
—-antagonists at muscarinic-receptor (M1, M2, M3, M5)
—agonist at M4
unique thing about clozpane mechanism compared to other antipsychotics?
high affinity at D4
weak at D2
More active at limbic
less active at striatal
why clozapine is thougt to be more EPSE safe?
weak at D2
clozapine main metabolizer cyp?
cyp1a2
what does smoking do to clozapine
reduce in blood (induce cyp1a2)
what does coffeee do to clozapine?
increase in blood ( inhibit cyp1a2)
is it absolute necessary to avoid coffee in clozapine therapy?
no, just don’t fluctuate the amount consumed
drugs that increase clozapine level?
SEC
—-
SSRIs
Erythromycin
Caffeine
drugs that decrease clozapine level?
PCT
Phenytoin
Carbamazepine
Tobacco
main active clozapine metabolite
- nor clozapine (n-desmethyl clozapine)
- Clozapine N-Oxide
side effects of clozapine (losing)
Nausea
Vomitting
Salivation
side effects of clozapine (gaining)
constipation
weight gain
dyspepsia
side effects of clozapine (sleepy)
Dizziness
Sedation
Insomnia
rate of hypertention in clozapine therapy
1/100
prevalence of hypersalivation in clozapine therapy?
31%
risks of hypersalivations?
asphyxiation
pneumonia
embarrasing in society
when is hypersalivation worse?
at evening
when is usually hypersalivation seen in clozapine therapy/
early in therapy
RCT based medication used in hypersalivation?
-amisulpride
-propantheline
medication used in hypersalivation commonly but no data?
hyoscine hydrobromide
what does sympathetic stimulation do to saliva
increase protein contain
what does parasympathetic stimulation do to saliva
increase the flow
hypothesis for hypersalivation due to clozpaine
- reduced swallowing
- a 2 adrenoceptor antagonist increases saliva
-M4 agonist
Adverse events associated with clozapine?
pancreatitis
agranulocytosis
myocarditis
seizure
severe orthost. hypotension
mortality in the elderly and dementia cases
colitis
thrombocytopenia
insulin resistant
thromboembolism
prevalence of diabetes in clozapine
33%
which conditions BNF requries caution about in clozapine therapy?
Above 60
Prostatic hypertrophy
Susceptible to angle closure glaucoma
is there any therapeutic window established for clozapine
no
What is generally accepted as the level required to trigger a therapeutic response in clozapine therapy?
0.35 mg/l
what level indicate caution in clozapine therapy?
above 0.5 mg/l
prevalence of clozapine induced myocarditis?
1/500
when do myocarditis happen in the course of clozapine therapy
80% in first 4 week
90% in first 8 weeks
what pathology suggests in post mortum analysis of clozapine-induced myocarditis?
Type 1 Ig E- mediated acute hypersensitivity reaction
findings of pathological analysis of clozapine induced myocarditis(CIM)?
infiltration of eosinophils and myocytes
will recurrent myocarditis happen in a subsequent restart of clozapine?
yes
features of myocarditis(CIM)?
Fever flu like
chest pain
dyspnoea
palpitation
tackycardia
ECG changes (prolongation)
Elevated oesinophils and cardiac enzymes
gold standard to Rx clozapine induced myocariditis (CIM)?
biopsy
biomarkers of CIM
Creatine Kinase
Lactate dehydrogenase
Aspartate aminotransferase
Myoglobin
Troponin
what troponin type is specifict to CIM?
Troponin I & T
mortality rate in CIM?
50%
contraindication for clozapine?
paralytic ileus
Epilepsy (uncontrolled)
Unable to undergo regular blood tests
hx of agranulocytosis
concomitant use of depot
impaired bone marrow
renal, cardiac or liver diseases
what are two completely atypical antipsychotics?
clozapine
and
possibly quetiapine
