IC5 GI symptoms

Question 1

Peripheral pathway – Gut – predominantly __ phase of CINV, mediated by ____

Answer 1

acute, 5HT3

Question 2

Central pathway – CNS – predominantly___ phase of CINV; mediated by ____

Answer 2

delayed, NK1 receptor & substance P

Question 3

Freq of emesis in IV drugs: high risk

Answer 3

> 90%

Question 4

Which IV drug has a high emesis risk

Answer 4

AC combination containing anthracycline or cyclophosphamide

Question 5

Freq of emesis in IV drugs: moderate risk

Answer 5

> 30 - 90 %

Question 6

Freq of emesis in IV drugs: low risk

Answer 6

10-30%

Question 7

Freq of emesis in IV drugs: minimal risk

Answer 7

< 10%

Question 8

Freq of emesis in oral drugs: moderate- high risk

Answer 8

≥ 30%

Question 9

Freq of emesis in oral drugs: minimal - low risk

Answer 9

< 30%

Question 10

Regimen for high emetogenic risk

Answer 10

Acute (day 1):
- NK1 antagonist + 5HT3 antagonist + Dexa + / - Olanzapine

Delayed (day 2 onwards):
- DEXA D2- 4
- Olanzapine D2-4 if used

Question 11

Dose for Aprepitant (Emend)

Answer 11

PO 125mg OD Day 1, 80mg OD Day 2, Day 3

Question 12

Example of NK1 antagonist

Answer 12

Aprepitant (Emend)

Question 13

Examples of 5HT3 antagonist

Answer 13

Ondansetron; Granisetron

Question 14

Dosing for ondansetron

Answer 14

IV/PO Ondansetron 8-16mg OD Day 1

Question 15

Dosing for granisetron

Answer 15

IV/PO Granisetron 1mg OD Day 1

Question 16

Combination NK1 + 5HT3 antagonist

Answer 16

Netupitant 300mg + Palonosetron 0.5mg (Akynzeo®)

Question 17

Dosing for Akynzeo

Answer 17

PO 1 capsule OD Day 1

Question 18

Dosing for dexamethasone

Answer 18

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

Question 19

Dosing for metoclopramide

Answer 19

IV/ PO Metoclopramide 10mg OD-TDS

Question 20

MOA of NK-1 antagonist

Answer 20

• Binds to NK-1 receptors, which prevents substance P (nociceptive neurotransmitter) from binding.
• Attenuates vagal afferent signals and exert antiemetic effect

Question 21

Adverse effects: NK-1 antagonist

Answer 21

Low frequency of fatigue, weakness, nausea, hiccups

Question 22

Drug Interactions with NK-1 antagonist

Answer 22

• Steroid, warfarin
• Benzodiazepines (increase benzodiazepine concentrations due to reduced metabolism)
• Certain chemotherapy eg Ifosfamide (decreases metabolism of ifosfamide)

Question 23

MOA: 5HT3 antagonist

Answer 23

Block 5HT-3 receptors peripherally in the gastrointestinal tract and centrally in the medulla

Question 24

Granisetron VS Ondansetron: which one is longer acting?

Answer 24

Granisetron

Question 25

Adverse effects: 5HT3 antagonist

Answer 25

- Headache and constipation - QTc prolongation (black box warning)

Question 26

Dosing for dexamethasone

Answer 26

IV/PO 12mg OD D1, IV/PO 8mg OD D2 onwards for highly emetogenic regimens

Question 27

AE for dexamethasone

Answer 27

More common: transient elevations in glucose, insomnia, anxiety, and gastric upset Less common: psychosis, reactivation of ulcers

Question 28

MOA of olanzapine

Answer 28

Antagonist of multiple receptors involved in CINV: dopamine, serotonin, histamine, cholinergic

Question 29

Dosing for olanzapine

Answer 29

5mg–10mg OD, consider lower doses (2.5mgOD) for elderly

Question 30

AE for olanzapine

Answer 30

Fatigue, sedation, postural hypotension, anticholinergic side effects

Question 31

MOA of metoclopramide

Answer 31

- Blocks dopamine receptors in chemoreceptor trigger zone - Antagonises peripheral serotonin receptors in intestines - Stimulates cholinergic activity in the gut, increasing gut motility (forward movement)

Question 32

Avoid prescribing metoclopramide with ___. Why?

Answer 32

Olanzapine; Higher risk of EPSE (tardive dyskinesias, neuroleptic malignant syndrome)

Question 33

AE of metoclopramide

Answer 33

Mild sedation and diarrhea, extrapyramidal reactions (e.g., dystonia, akathisia)

Question 34

Drug for anticipatory CINV

Answer 34

Benzodiazepines

Question 35

Dosing for benzodiazepines

Answer 35

- PO alprazolam 0.5-1mg OR - PO lorazepam 0.5-2mg on the night before treatment and then 1-2h before chemotherapy begins

Question 36

AE for benzodiazepines

Answer 36

Drowsiness, dizziness, hypotension, anterograde amnesia, paradoxical reactions (hyperactive, aggressive behaviour)

Question 37

____requires antidiarrheal prophylaxis with loperamide for first two cycles

Answer 37

Neratinib

Question 38

Risk factors for CID

Answer 38

- > 65 yo - Female - ECOG performance status ≥ 2 - Bowel inflammation or malabsorption - Bowel malignancy - Biliary obstruction

Question 39

CID grade 1

Answer 39

Incr of < 4 stools/ day above baseline

Question 40

CID grade 2

Answer 40

Incr of 4-6 stools/ day above baseline; Limited ADL

Question 41

CID grade 3

Answer 41

Incr of ≥ 7 stools/ day above baseline; Hospitalisation needed, Limiting self-care

Question 42

CID grade 4

Answer 42

Life-threatening, Urgent intervention needed

Question 43

CID grade 5

Answer 43

Death

Question 44

Uncomplicated diarrhea

Answer 44

- Grade 1 or 2 CID - No complicating s/sx

Question 45

Complicated diarrhea

Answer 45

- Grade 3 or 4 CID - Grade 1 or 2 CID with 1 or more of the following: Fever Sepsis Neutropenia Frank bleeding > Grade 2 N/V Cramping Dehydration Decr performance status

Question 46

Treatment for uncomplicated diarrhea

Answer 46

- Loperamide - Oral rehydration - Diet modifications - Withhold chemo for grade 2

Question 47

Tx for complicated diarrhea

Answer 47

- Admit to hosp - Withhold chemo - IV fluids & antibiotics - Octreotide

Question 48

MOA of loperamide

Answer 48

opioid that inhibits smooth-muscle contraction of intestine to decrease motility (primary neurotransmitter is acetylcholine)

Question 49

MOA for octreotide

Answer 49

Causes decreased hormone secretion, which increases transit time within intestine, decreases secretion of fluid, and increases absorption of fluid and electrolytes

Question 50

Octreotide is beneficial for patients with ____ and ____-induced CID

Answer 50

5-FU; irinotecan

Question 51

Dosing for octreotide

Answer 51

SQ 100-150mcg TDS OR IV 25-50mcg/hour Max 500mcg TDS

Question 52

Up to 10% of patients experience ___-induced lactose intolerance due to lose of lactase activity (temporary)

Answer 52

5-FU

Question 53

Irinotecan is converted primarily in the liver to active metabolite ___ which is responsible for causing diarrhea

Answer 53

SN-38

Question 54

SN-38 is deactivated by glucuronidation via ____ to ____

Answer 54

UDP-GT1A1; SN38-G

Question 55

What gene causes decr expression of UGT1A1

Answer 55

Homozygous for UGT1A1*28

Question 56

How is SN38-G reactivated back to form SN-38

Answer 56

Bacteria found in gut produce β-glucuronidases which reactivate SN38-G via deconjugation

Question 57

Mean sx duration for iritotecan-induced diarrhea

Answer 57

30 mins

Question 58

MOA of irinotecan

Answer 58

Irinotecan is a selective, reversible inhibitor of acetylcholine esterase leading to a cholinergic response

Question 59

Tx for irinotecan-induced diarrhea in EARLY onset

Answer 59

SQ/IV atropine 0.25–1 mg (maximum 1.2 mg); usually SQ

Question 60

MOA for atropine

Answer 60

inhibits acetylcholine at muscarinic receptor as a competitive antagonist

Question 61

Late onset of irinotecan-induced diarrhea for weekly dosing

Answer 61

11 days

Question 62

Late onset of irinotecan-induced diarrhea for every 3 weeks dosing

Answer 62

6 days

Question 63

Tx for irinotecan-induced diarrhea in LATE onset

Answer 63

Loperamide 4 mg after first loose bowel movement, then 2 mg every 2 hours (4 mg every 4 hours at night) until 12 hours have passed without bowel movement

Question 64

Which grp of patients are NOT suited to use enema/ suppositories for constipation

Answer 64

- Low WBC/ platelet - Immunocompromised Due to risk of infection/ bleeding