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Pharmacology > Clozapine > Flashcards

Clozapine Flashcards

1
Q

Clozapine class of antipsychotic

A

Atypical

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2
Q

Clozapine chemical structure

A

Tricyclic dibenzodiazepine

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3
Q

Dopamine receptor which clozapine has high affinity for

A

D4

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4
Q

Mechanism of action of clozapine

A 
5HT2 > D2 blockade
D4 blockade
5HT6 blockade
Alpha 1 antagonist
Muscarinic receptor antagonist
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5
Q

Site of dopamine receptor where clozapine is most active

A

Limbic dopamine receptors

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6
Q

Proposed reason why clozapine has lower rates of EPSEs

A

More active at limbic than striatal dopamine receptors

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7
Q

Effect of dopamine on prolactin levels

A

Little to no effect

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8
Q

CYP enzyme which mainly metabolises clozapine

A

CYP1A2

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9
Q

Effect of caffeine on clozapine levels

A

Increases

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10
Q

Effect of cigarette smoking on clozapine levels

A

Decreases

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11
Q

Decrease in clozapine levels following 5 days off caffeine

A

Decreased by up to 50%

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12
Q

Effect of SSRIs on clozapine levels

A

Increases

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13
Q

Effect of erythromycin on clozapine levels

A

Increases

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14
Q

Effect of carbamazepine on clozapine levels

A

Decreases

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15
Q

Effect of phenytoin on clozapine levels

A

Decreases

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16
Q

Active metabolites of clozapine

A

N-desmethylclozapine

Clozapine N-oxide

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17
Q

Percentage of patients on clozapine who develop hypersalivation

A

31%

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18
Q

Point in clozapine therapy when hypersalivation is worst

A

Early on

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19
Q

Percentage of patients on clozapine who develop agranulocytosis

A

1%

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20
Q

Time after starting clozapine with the highest risk of developing agranulocytosis

A

4 to 18 weeks

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21
Q

Adverse effects of clozapine

A 
Agranulocytosis
Myocarditis
Seizures
Orthostatic hypotension
Colitis
Pancreatitis
Thrombocytopaenia
Thromboembolism
Insulin resistance and diabetes mellitus
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22
Q

Lower level of clozapine usually required for a therapeutic response

A

0.35mg/l

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23
Q

Level of clozapine at which there is an increased seizure risk

A

0.5mg/l

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24
Q

Time frame from starting clozapine by which time 80% of cases of myocarditis occur

A

Within 4 weeks of starting

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25
Physical features of myocarditis
Fever Chest pain Tachycardia Dyspnoea
26
Laboratory features of myocarditis
Raised eosinophils | Raised cardiac enzymes
27
Gold standard investigation to diagnose myocarditis
Endomyocardial biopsy
28
Number of weeks after starting clozapine where weekly WCC monitoring is usually required
26 weeks
29
Consequence of a red WCC result when clozapine monitoring
Must be stopped and never tried again
30
Consequence of a yellow WCC result when clozapine monitoring
Monitoring frequency must be increased until a green signal is obtained
31
Non-dose related adverse effects of clozapine
Myocarditis | Agranulocytosis
32
Antidepressant which can precipitate clozapine-related neutropaenia
Paroxetine
33
Classes of receptors affected by clozapine
``` Dopaminergic Histaminergic Serotonergic Adrenergic Cholinergic ```
34
When WCC should be checked while on clozapine
Weekly for 26 weeks | Fortnightly or monthly afterwards
35
Maximum clozapine dose
900mg/day
36
Speed of release of clozapine from D2 receptors
Fast release
37
Risk of fatal agranulocytosis in patients on clozapine without monitoring
1 in 4250
38
Risk of fatal agranulocytosis in patients on clozapine with monitoring
<1 in 8000
39
WCC causing a red alert for clozapine
<3
40
WCC causing an amber alert for clozapine
3-3.5
41
Neutrophil count causing a red alert for clozapine
<1.5
42
Neutrophil count causing an amber alert for clozapine
1.5-2
43
Neutrophil count causing an amber alert for clozapine
1.5-2
44
Result of an amber alert while taking clozapine
Twice weekly blood count required until numbers stabilise or improve
45
Result of an amber alert while taking clozapine
Twice weekly blood count required until numbers stabilise or improve
46
Treatments used in clozapine induced hypersalivation
``` Amitriptyline Benzatropine Trihexyphenidyl Hyoscine Pirenzepine (unlicensed) ```
47
Time frame for cardiomyopathy to develop while on clozapine
Can develop at any time - median 9 months
48
Most common cardiac side effect of clozapine
Tachycardia
49
Demographic at highest risk for clozapine induced agranulocytosis
Young, Afro-Caribbean, female
50
Risk of agranulocytosis in a patient taking clozapine after one year (risk highest in first 18 weeks)
0.01%
51
Prevalence of agranulocytosis during clozapine treatment
0.4%
52
Important factor increasing the risk of clozapine-induced constipation
Inpatient mental health treatment
53
Most common side effects of clozapine
Weight gain Constipation Tachycardia
54
Demographic who usually have lower plasma clozapine levels
Young Male Smoker
55
Demographic who usually have higher clozapine levels
Asian Non-smoker Female Older
56
Laxative which should not be used for clozapine induced constipation
Lactulose
57
Medications which may be used for clozapine induced neutropaenia
G-CSF | Lithium
58
Antipsychotic which can be used to treat clozapine related weight gain
Aripiprazole
59
Medication licensed to treat clozapine induced hypersalivation
Hyoscine hydrobromide
60
Unlicensed medications which can help with clozapine induced hypersalivation
Trihexyphenidyl Benzhexol Pirenzepine
61
Maximum daily dose of clozapine
900mg/day

Pharmacology (34 decks)

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