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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
Q

Physical features of myocarditis

A

Fever
Chest pain
Tachycardia
Dyspnoea

26
Q

Laboratory features of myocarditis

A

Raised eosinophils

Raised cardiac enzymes

27
Q

Gold standard investigation to diagnose myocarditis

A

Endomyocardial biopsy

28
Q

Number of weeks after starting clozapine where weekly WCC monitoring is usually required

A

26 weeks

29
Q

Consequence of a red WCC result when clozapine monitoring

A

Must be stopped and never tried again

30
Q

Consequence of a yellow WCC result when clozapine monitoring

A

Monitoring frequency must be increased until a green signal is obtained

31
Q

Non-dose related adverse effects of clozapine

A

Myocarditis

Agranulocytosis

32
Q

Antidepressant which can precipitate clozapine-related neutropaenia

A

Paroxetine

33
Q

Classes of receptors affected by clozapine

A 
Dopaminergic
Histaminergic
Serotonergic
Adrenergic
Cholinergic
34
Q

When WCC should be checked while on clozapine

A

Weekly for 26 weeks

Fortnightly or monthly afterwards

35
Q

Maximum clozapine dose

A

900mg/day

36
Q

Speed of release of clozapine from D2 receptors

A

Fast release

37
Q

Risk of fatal agranulocytosis in patients on clozapine without monitoring

A

1 in 4250

38
Q

Risk of fatal agranulocytosis in patients on clozapine with monitoring

A

<1 in 8000

39
Q

WCC causing a red alert for clozapine

A

<3

40
Q

WCC causing an amber alert for clozapine

A

3-3.5

41
Q

Neutrophil count causing a red alert for clozapine

A

<1.5

42
Q

Neutrophil count causing an amber alert for clozapine

A

1.5-2

43
Q

Neutrophil count causing an amber alert for clozapine

A

1.5-2

44
Q

Result of an amber alert while taking clozapine

A

Twice weekly blood count required until numbers stabilise or improve

45
Q

Result of an amber alert while taking clozapine

A

Twice weekly blood count required until numbers stabilise or improve

46
Q

Treatments used in clozapine induced hypersalivation

A 
Amitriptyline
Benzatropine
Trihexyphenidyl
Hyoscine
Pirenzepine (unlicensed)
47
Q

Time frame for cardiomyopathy to develop while on clozapine

A

Can develop at any time - median 9 months

48
Q

Most common cardiac side effect of clozapine

A

Tachycardia

49
Q

Demographic at highest risk for clozapine induced agranulocytosis

A

Young, Afro-Caribbean, female

50
Q

Risk of agranulocytosis in a patient taking clozapine after one year (risk highest in first 18 weeks)

A

0.01%

51
Q

Prevalence of agranulocytosis during clozapine treatment

A

0.4%

52
Q

Important factor increasing the risk of clozapine-induced constipation

A

Inpatient mental health treatment

53
Q

Most common side effects of clozapine

A

Weight gain
Constipation
Tachycardia

54
Q

Demographic who usually have lower plasma clozapine levels

A

Young
Male
Smoker

55
Q

Demographic who usually have higher clozapine levels

A

Asian
Non-smoker
Female
Older

56
Q

Laxative which should not be used for clozapine induced constipation

A

Lactulose

57
Q

Medications which may be used for clozapine induced neutropaenia

A

G-CSF

Lithium

58
Q

Antipsychotic which can be used to treat clozapine related weight gain

A

Aripiprazole

59
Q

Medication licensed to treat clozapine induced hypersalivation

A

Hyoscine hydrobromide

60
Q

Unlicensed medications which can help with clozapine induced hypersalivation

A

Trihexyphenidyl
Benzhexol
Pirenzepine

61
Q

Maximum daily dose of clozapine

A

900mg/day

Pharmacology (34 decks)

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