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Chemotherapy Induced N/V Flashcards

1
Q

Which phase is CNS pathway predominant?

A

Delayed

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2
Q

Which phase is peripheral pathway (gut) predominant?

A

Acute

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3
Q

Onset of acute phase

A

1-2 hours after administration

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4
Q

Peak intensity of acute phase

A

Within 5-6 hours

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5
Q

Resolution of acute phase

A

At 12-24 hours

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6
Q

Peak onset of delayed phase

A

48-72 hours after chemotherapy
Diminish in 1-3 days

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7
Q

What is breakthrough CINV?

A

N/V occurring despite preventive treatment

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8
Q

What is refractory CINV?

A

N/V occurring during subsequent cycles of chemotherapy when antiemetic prophylaxis or rescue therapy has failed in previous cycle

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9
Q

What are the 2 guidelines for CINV?

A
  • ASCO
  • NCCN
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10
Q

Frequency of HIGH emetic risk (IV)

A

> 90%

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11
Q

Frequency of MODERATE emetic risk (IV)

A

> 30-90%

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12
Q

Frequency of LOW emetic risk (IV)

A

10-30%

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13
Q

Frequency of MINIMAL emetic risk (IV)

A

<10%

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14
Q

Frequency of MODERATE to HIGH emetic risk (PO)

A

≥30%

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15
Q

Frequency of MINIMAL to LOW emetic risk (PO)

A

<30%

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16
Q

Patient risk factors for CINV - 7

A
  1. <50 years old
  2. Female
  3. Hx of low prior chronic alcohol intake (<1 glass)
  4. Hx of previous chemotherapy induced emesis
  5. Hx of motion sickness
  6. Hx of emesis during pregnancy
  7. Anxiety
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17
Q

Antiemetic combination for high risk

A

NK1+ 5HT3 + DEX +/- OLA
DEX D2-4 + OLA D2-4

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18
Q

Antiemetic combination for moderate risk

A

5HT3 + DEX
DEX D2-3

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19
Q

Antiemetic combination for low risk

A

5HT3 or DEX or DOPA

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20
Q

NK1 antagonist

A

Aprepitant (Emend)

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21
Q

Dose of Aprepitant

A

PO
Day 1: 125mg OD
Day 2-3: 80mg OD

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22
Q

5HT3 antagonist

A

Ondansetron
Granisetron

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23
Q

Dose of Ondansetron

A

IV/PO
Day 1: 8-16mg OD
Day 2 onwards: 8mg BD

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24
Q

Dose of Granisetron

A

Day 1: 1mg OD
Day 2 onwards: 1mg OM

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25
Q

Combination of NK1 + 5HT3

A

Akynzeo - Netupitant 300mg + Palonosetron 0.5mg

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26
Q

Dose of Akynzeo

A

PO
Day 1: 1 capsule OD

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27
Q

Dose of Dexamethasone

A

IV/PO
Day 1: 12mg OD
Day 2 onwards: 8mg OD

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28
Q

Dopamine antagonist

A

Metoclopramide

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29
Q

Dose of Metoclopramide

A

IV/PO
10mg OD-TDS

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30
Q

NK1 place in therapy

A

Prevents acute and delayed CINV

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31
Q

MOA of NK1 antagonist

A
  1. Binds to NK1 receptors, which prevents substance P (nociceptive neurotransmitter) from binding
  2. Attenuates vagal afferent signals
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32
Q

Which NK1 antagonist requires 3 day course?

A

Aprepitant

33
Q

Common AE of NK1 antagonist

A

Low frequency of fatigue, weakness, nausea, hiccups

34
Q

DDI with NK1 antagonist - 4

A
  1. Steroids
  2. Warfarin
  3. BZDs
  4. Certain chemotherapy e.g. ifosfamide
35
Q

MOA of ifosfamide - NK1 antagonist DDI

A

Decreases metabolism of ifosfamide

36
Q

MOA of steroids - NK1 antagonist DDI

A

Increased plasma concentration of steroids

37
Q

MOA of warfarin - NK1 antagonist DDI

A

Decrease plasma concentration of warfarin (decrease INR)

38
Q

MOA of BZD - NK1 antagonist DDI

A

Increase BZD concentration due to reduced metabolism

39
Q

5HT3 antagonist place in therapy

A

Prevents acute CINV

40
Q

MOA of 5HT3 antagonist

A

Blocks 5HT3 receptors peripherally in GIT and centrally in medulla

41
Q

Between Ondanstetron and Granisetron, which is longer acting?

A

Granisetron

42
Q

Adverse effects of 5HT3 antagonist

A
  1. Headache
  2. Constipation
  3. QTc prolongation !!!!
43
Q

Dexamethasone place in therapy

A

Prevents acute and delayed CINV

44
Q

Most common AEs of Dexamethasone

A
  1. Transient elevations in glucose
  2. Insomnia
  3. Anxiety
  4. Gastric upset
45
Q

Less common AEs of Dexamethasone

A
  1. Psychosis (paediatric patients)
  2. Reactivation of ulcers (take with or after food)
46
Q

What class of medication is Olanzapine?

A

Atypical antipsychotic

47
Q

Olanzapine place in therapy

A

Prevents acute and delayed CINV

48
Q

MOA of Olanzapine

A

Antagonists of multiple receptors involved in CINV - dopamine, serotonin, histamine, cholinergic

49
Q

Dose of Olanzapine

A

5-10mg OD
2.5mg OD for elderly

50
Q

Adverse effects of Olanzapine

A
  1. Fatigue
  2. Sedation
  3. Postural hypotension
  4. Anticholinergic SEs
51
Q

Metoclopramide place in therapy

A

Prevents acute CINV in low emetogenic regimens
Useful for breakthrough CINV

52
Q

Which agent is useful for breakthrough CINV?

A

Metoclopramide

53
Q

Adverse effects of Metoclopramide

A

Mild sedation & diarrhoea
Extrapyramidal reactions (e.g. dystonia, akathisia)

54
Q

What drug should be avoided with Metoclopramide?

A

Olanzapine

55
Q

Why should Metoclopramide and Olanzapine combination be avoided?

A

Increases risk of extrapyramidal reactions (tardive dyskinesias, neuroleptic malignant syndrome)

56
Q

BZD place in therapy

A

Useful for anticipatory CINV

57
Q

What agents are useful for anticipatory CINV?

A

BZDs - alprazolam or lorazepam

58
Q

MOA of BZDs

A

Binds to BZD receptors on postsynaptic GABA of neuron to enhance inhibitory effect of GABA
Leads to sedation, reduction in anxiety and possible depression of the vomiting centre

59
Q

Dose of Alprazolam

A

PO 0.5-1mg on the night before treatment and 1-2 hours before chemotherapy

60
Q

Dose of Lorazepam

A

PO 0.5-2mg on the night before treatment and 1-2 hours before chemotherapy

61
Q

Adverse effects of BZDs

A
  1. Drowsiness
  2. Dizziness
  3. Hypotention
  4. Anterograde amnesia
  5. Paradoxical reactions (hyperactive, aggressive behaviour)
62
Q

Caution of BZDs

A

In elderly (risk of falls - prescribe lowest effective dose)

63
Q

Adjunctive agents for CINV

A

Butyrophenones (haloperidol)
Phenothiazines (prochlorperazine, chlorpromazine, promethazine)

64
Q

Adjunctive agents place in therapy

A

May be considered in refractory CINV

65
Q

Haloperidol MOA

A

Block dopamine receptors in the chemoreceptor trigger zone

66
Q

Dose of Haloperidol

A

PO/IV
0.5-2mg q4-6hr

67
Q

Adverse effects of Haloperidol

A

Sedation, extrapyramidal symptoms

68
Q

MOA of phenothiazines

A

Block dopamine receptors in the chemoreceptor trigger zone

69
Q

Dose of prochlorperazine

A

PO 10mg TDS/QDS PRN

70
Q

Adverse effects of phenothiazines

A

Drowsiness, hypotension, akathisia, dystonia, extrapyramidal symptoms

71
Q

General principle of breakthrough CINV

A

Additional agent from different drug class (different MOA)

72
Q

Non-pharmacological for CINV (no. 1)

A

Small, frequent meals
Avoid heavy meals

73
Q

Non-pharmacological for CINV (no. 2)

A

Avoid greasy, spicy, very sweet or salty food, and food with strong flavours or smells

74
Q

Non-pharmacological for CINV (no. 3)

A

Sip small amount of fluid often instead of a full glass at once

75
Q

Non-pharmacological for CINV (no. 4)

A

Avoid caffeinated beverages

76
Q

Non-pharmacological for CINV (no. 5)

A

Avoid lying flat for 2 hours after eating

77
Q

Anticipatory CINV

A
  1. Prevention
  2. Behavioural therapy
  3. Acupuncture/acupressure
  4. Consider use of BZDs before treatment
78
Q

Behavioural therapy for anticipatory CINV

A

a. Relaxation/systematic desensitisation
b. Hypnosis/guided imagery
c. Music therapy

Multi-morbid (5 decks)

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