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PR4152 > IC5 GI symptoms > Flashcards

IC5 GI symptoms Flashcards

1
Q

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

A

acute, 5HT3

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2
Q

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

A

delayed, NK1 receptor & substance P

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3
Q

Freq of emesis in IV drugs: high risk

A

> 90%

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4
Q

Which IV drug has a high emesis risk

A

AC combination containing anthracycline or cyclophosphamide

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5
Q

Freq of emesis in IV drugs: moderate risk

A

> 30 - 90 %

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6
Q

Freq of emesis in IV drugs: low risk

A

10-30%

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7
Q

Freq of emesis in IV drugs: minimal risk

A

< 10%

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8
Q

Freq of emesis in oral drugs: moderate- high risk

A

≥ 30%

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9
Q

Freq of emesis in oral drugs: minimal - low risk

A

< 30%

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10
Q

Regimen for high emetogenic risk

A

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

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

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11
Q

Dose for Aprepitant (Emend)

A

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

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12
Q

Example of NK1 antagonist

A

Aprepitant (Emend)

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13
Q

Examples of 5HT3 antagonist

A

Ondansetron; Granisetron

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14
Q

Dosing for ondansetron

A

IV/PO Ondansetron 8-16mg OD Day 1

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15
Q

Dosing for granisetron

A

IV/PO Granisetron 1mg OD Day 1

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16
Q

Combination NK1 + 5HT3 antagonist

A

Netupitant 300mg + Palonosetron 0.5mg (Akynzeo®)

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17
Q

Dosing for Akynzeo

A

PO 1 capsule OD Day 1

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18
Q

Dosing for dexamethasone

A

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

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19
Q

Dosing for metoclopramide

A

IV/ PO Metoclopramide 10mg OD-TDS

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20
Q

MOA of NK-1 antagonist

A
  • Binds to NK-1 receptors, which prevents substance P (nociceptive neurotransmitter) from binding.
  • Attenuates vagal afferent signals and exert antiemetic effect
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21
Q

Adverse effects: NK-1 antagonist

A

Low frequency of fatigue, weakness, nausea, hiccups

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22
Q

Drug Interactions with NK-1 antagonist

A
  • Steroid, warfarin
  • Benzodiazepines (increase benzodiazepine concentrations due to reduced metabolism)
  • Certain chemotherapy eg Ifosfamide (decreases metabolism of ifosfamide)
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23
Q

MOA: 5HT3 antagonist

A

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

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24
Q

Granisetron VS Ondansetron: which one is longer acting?

A

Granisetron

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25
Q

Adverse effects: 5HT3 antagonist

A
  • Headache and constipation
  • QTc prolongation (black box warning)
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26
Q

Dosing for dexamethasone

A

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

27
Q

AE for dexamethasone

A

More common: transient elevations in glucose, insomnia, anxiety, and gastric upset

Less common: psychosis, reactivation of ulcers

28
Q

MOA of olanzapine

A

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

29
Q

Dosing for olanzapine

A

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

30
Q

AE for olanzapine

A

Fatigue, sedation, postural hypotension, anticholinergic side effects

31
Q

MOA of metoclopramide

A
  • Blocks dopamine receptors in chemoreceptor trigger zone
  • Antagonises peripheral serotonin receptors in intestines
  • Stimulates cholinergic activity in the gut, increasing gut motility (forward movement)
32
Q

Avoid prescribing metoclopramide with ___. Why?

A

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

33
Q

AE of metoclopramide

A

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

34
Q

Drug for anticipatory CINV

A

Benzodiazepines

35
Q

Dosing for benzodiazepines

A
  • PO alprazolam 0.5-1mg OR
  • PO lorazepam 0.5-2mg

on the night before treatment and then 1-2h before chemotherapy begins

36
Q

AE for benzodiazepines

A

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

37
Q

____requires antidiarrheal prophylaxis with loperamide for first two cycles

A

Neratinib

38
Q

Risk factors for CID

A
  • > 65 yo
  • Female
  • ECOG performance status ≥ 2
  • Bowel inflammation or malabsorption
  • Bowel malignancy
  • Biliary obstruction
39
Q

CID grade 1

A

Incr of < 4 stools/ day above baseline

40
Q

CID grade 2

A

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

41
Q

CID grade 3

A

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

42
Q

CID grade 4

A

Life-threatening,
Urgent intervention needed

43
Q

CID grade 5

A

Death

44
Q

Uncomplicated diarrhea

A
  • Grade 1 or 2 CID
  • No complicating s/sx
45
Q

Complicated diarrhea

A
  • 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
46
Q

Treatment for uncomplicated diarrhea

A
  • Loperamide
  • Oral rehydration
  • Diet modifications
  • Withhold chemo for grade 2
47
Q

Tx for complicated diarrhea

A
  • Admit to hosp
  • Withhold chemo
  • IV fluids & antibiotics
  • Octreotide
48
Q

MOA of loperamide

A

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

49
Q

MOA for octreotide

A

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

50
Q

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

A

5-FU; irinotecan

51
Q

Dosing for octreotide

A

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

Max 500mcg TDS

52
Q

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

A

5-FU

53
Q

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

A

SN-38

54
Q

SN-38 is deactivated by glucuronidation via ____ to ____

A

UDP-GT1A1; SN38-G

55
Q

What gene causes decr expression of UGT1A1

A

Homozygous for UGT1A1*28

56
Q

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

A

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

57
Q

Mean sx duration for iritotecan-induced diarrhea

A

30 mins

58
Q

MOA of irinotecan

A

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

59
Q

Tx for irinotecan-induced diarrhea in EARLY onset

A

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

60
Q

MOA for atropine

A

inhibits acetylcholine at muscarinic receptor as a competitive antagonist

61
Q

Late onset of irinotecan-induced diarrhea for weekly dosing

A

11 days

62
Q

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

A

6 days

63
Q

Tx for irinotecan-induced diarrhea in LATE onset

A

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

64
Q

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

A
  • Low WBC/ platelet
  • Immunocompromised

Due to risk of infection/ bleeding

PR4152 (7 decks)

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