Clozapine Flashcards
Clozapine class of antipsychotic
Atypical
Clozapine chemical structure
Tricyclic dibenzodiazepine
Dopamine receptor which clozapine has high affinity for
D4
Mechanism of action of clozapine
5HT2 > D2 blockade D4 blockade 5HT6 blockade Alpha 1 antagonist Muscarinic receptor antagonist
Site of dopamine receptor where clozapine is most active
Limbic dopamine receptors
Proposed reason why clozapine has lower rates of EPSEs
More active at limbic than striatal dopamine receptors
Effect of dopamine on prolactin levels
Little to no effect
CYP enzyme which mainly metabolises clozapine
CYP1A2
Effect of caffeine on clozapine levels
Increases
Effect of cigarette smoking on clozapine levels
Decreases
Decrease in clozapine levels following 5 days off caffeine
Decreased by up to 50%
Effect of SSRIs on clozapine levels
Increases
Effect of erythromycin on clozapine levels
Increases
Effect of carbamazepine on clozapine levels
Decreases
Effect of phenytoin on clozapine levels
Decreases
Active metabolites of clozapine
N-desmethylclozapine
Clozapine N-oxide
Percentage of patients on clozapine who develop hypersalivation
31%
Point in clozapine therapy when hypersalivation is worst
Early on
Percentage of patients on clozapine who develop agranulocytosis
1%
Time after starting clozapine with the highest risk of developing agranulocytosis
4 to 18 weeks
Adverse effects of clozapine
Agranulocytosis Myocarditis Seizures Orthostatic hypotension Colitis Pancreatitis Thrombocytopaenia Thromboembolism Insulin resistance and diabetes mellitus
Lower level of clozapine usually required for a therapeutic response
0.35mg/l
Level of clozapine at which there is an increased seizure risk
0.5mg/l
Time frame from starting clozapine by which time 80% of cases of myocarditis occur
Within 4 weeks of starting
Physical features of myocarditis
Fever
Chest pain
Tachycardia
Dyspnoea
Laboratory features of myocarditis
Raised eosinophils
Raised cardiac enzymes
Gold standard investigation to diagnose myocarditis
Endomyocardial biopsy
Number of weeks after starting clozapine where weekly WCC monitoring is usually required
26 weeks
Consequence of a red WCC result when clozapine monitoring
Must be stopped and never tried again
Consequence of a yellow WCC result when clozapine monitoring
Monitoring frequency must be increased until a green signal is obtained
Non-dose related adverse effects of clozapine
Myocarditis
Agranulocytosis
Antidepressant which can precipitate clozapine-related neutropaenia
Paroxetine
Classes of receptors affected by clozapine
Dopaminergic Histaminergic Serotonergic Adrenergic Cholinergic
When WCC should be checked while on clozapine
Weekly for 26 weeks
Fortnightly or monthly afterwards
Maximum clozapine dose
900mg/day
Speed of release of clozapine from D2 receptors
Fast release
Risk of fatal agranulocytosis in patients on clozapine without monitoring
1 in 4250
Risk of fatal agranulocytosis in patients on clozapine with monitoring
<1 in 8000
WCC causing a red alert for clozapine
<3
WCC causing an amber alert for clozapine
3-3.5
Neutrophil count causing a red alert for clozapine
<1.5
Neutrophil count causing an amber alert for clozapine
1.5-2
Neutrophil count causing an amber alert for clozapine
1.5-2
Result of an amber alert while taking clozapine
Twice weekly blood count required until numbers stabilise or improve
Result of an amber alert while taking clozapine
Twice weekly blood count required until numbers stabilise or improve
Treatments used in clozapine induced hypersalivation
Amitriptyline Benzatropine Trihexyphenidyl Hyoscine Pirenzepine (unlicensed)
Time frame for cardiomyopathy to develop while on clozapine
Can develop at any time - median 9 months
Most common cardiac side effect of clozapine
Tachycardia
Demographic at highest risk for clozapine induced agranulocytosis
Young, Afro-Caribbean, female
Risk of agranulocytosis in a patient taking clozapine after one year (risk highest in first 18 weeks)
0.01%
Prevalence of agranulocytosis during clozapine treatment
0.4%
Important factor increasing the risk of clozapine-induced constipation
Inpatient mental health treatment
Most common side effects of clozapine
Weight gain
Constipation
Tachycardia
Demographic who usually have lower plasma clozapine levels
Young
Male
Smoker
Demographic who usually have higher clozapine levels
Asian
Non-smoker
Female
Older
Laxative which should not be used for clozapine induced constipation
Lactulose
Medications which may be used for clozapine induced neutropaenia
G-CSF
Lithium
Antipsychotic which can be used to treat clozapine related weight gain
Aripiprazole
Medication licensed to treat clozapine induced hypersalivation
Hyoscine hydrobromide
Unlicensed medications which can help with clozapine induced hypersalivation
Trihexyphenidyl
Benzhexol
Pirenzepine
Maximum daily dose of clozapine
900mg/day