IC5 GI symptoms Flashcards
Peripheral pathway – Gut – predominantly __ phase of CINV, mediated by ____
acute, 5HT3
Central pathway – CNS – predominantly___ phase of CINV; mediated by ____
delayed, NK1 receptor & substance P
Freq of emesis in IV drugs: high risk
> 90%
Which IV drug has a high emesis risk
AC combination containing anthracycline or cyclophosphamide
Freq of emesis in IV drugs: moderate risk
> 30 - 90 %
Freq of emesis in IV drugs: low risk
10-30%
Freq of emesis in IV drugs: minimal risk
< 10%
Freq of emesis in oral drugs: moderate- high risk
≥ 30%
Freq of emesis in oral drugs: minimal - low risk
< 30%
Regimen for high emetogenic risk
Acute (day 1):
- NK1 antagonist + 5HT3 antagonist + Dexa + / - Olanzapine
Delayed (day 2 onwards):
- DEXA D2- 4
- Olanzapine D2-4 if used
Dose for Aprepitant (Emend)
PO 125mg OD Day 1, 80mg OD Day 2, Day 3
Example of NK1 antagonist
Aprepitant (Emend)
Examples of 5HT3 antagonist
Ondansetron; Granisetron
Dosing for ondansetron
IV/PO Ondansetron 8-16mg OD Day 1
Dosing for granisetron
IV/PO Granisetron 1mg OD Day 1
Combination NK1 + 5HT3 antagonist
Netupitant 300mg + Palonosetron 0.5mg (Akynzeo®)
Dosing for Akynzeo
PO 1 capsule OD Day 1
Dosing for dexamethasone
IV/PO 12mg OD Day 1, IV/PO 8mg OD Day 2 onwards
Dosing for metoclopramide
IV/ PO Metoclopramide 10mg OD-TDS
MOA of NK-1 antagonist
- Binds to NK-1 receptors, which prevents substance P (nociceptive neurotransmitter) from binding.
- Attenuates vagal afferent signals and exert antiemetic effect
Adverse effects: NK-1 antagonist
Low frequency of fatigue, weakness, nausea, hiccups
Drug Interactions with NK-1 antagonist
- Steroid, warfarin
- Benzodiazepines (increase benzodiazepine concentrations due to reduced metabolism)
- Certain chemotherapy eg Ifosfamide (decreases metabolism of ifosfamide)
MOA: 5HT3 antagonist
Block 5HT-3 receptors peripherally in the gastrointestinal tract and centrally in the medulla
Granisetron VS Ondansetron: which one is longer acting?
Granisetron
Adverse effects: 5HT3 antagonist
- Headache and constipation
- QTc prolongation (black box warning)
Dosing for dexamethasone
IV/PO 12mg OD D1, IV/PO 8mg OD D2 onwards for highly emetogenic regimens
AE for dexamethasone
More common: transient elevations in glucose, insomnia, anxiety, and gastric upset
Less common: psychosis, reactivation of ulcers
MOA of olanzapine
Antagonist of multiple receptors involved in CINV: dopamine, serotonin, histamine, cholinergic
Dosing for olanzapine
5mg–10mg OD, consider lower doses (2.5mgOD) for elderly
AE for olanzapine
Fatigue, sedation, postural hypotension, anticholinergic side effects
MOA of metoclopramide
- Blocks dopamine receptors in chemoreceptor trigger zone
- Antagonises peripheral serotonin receptors in intestines
- Stimulates cholinergic activity in the gut, increasing gut motility (forward movement)
Avoid prescribing metoclopramide with ___. Why?
Olanzapine; Higher risk of EPSE (tardive dyskinesias, neuroleptic malignant syndrome)
AE of metoclopramide
Mild sedation and diarrhea, extrapyramidal reactions (e.g., dystonia, akathisia)
Drug for anticipatory CINV
Benzodiazepines
Dosing for benzodiazepines
- PO alprazolam 0.5-1mg OR
- PO lorazepam 0.5-2mg
on the night before treatment and then 1-2h before chemotherapy begins
AE for benzodiazepines
Drowsiness, dizziness, hypotension, anterograde amnesia, paradoxical reactions (hyperactive, aggressive behaviour)
____requires antidiarrheal prophylaxis with loperamide for first two cycles
Neratinib
Risk factors for CID
- > 65 yo
- Female
- ECOG performance status ≥ 2
- Bowel inflammation or malabsorption
- Bowel malignancy
- Biliary obstruction
CID grade 1
Incr of < 4 stools/ day above baseline
CID grade 2
Incr of 4-6 stools/ day above baseline;
Limited ADL
CID grade 3
Incr of ≥ 7 stools/ day above baseline;
Hospitalisation needed,
Limiting self-care
CID grade 4
Life-threatening,
Urgent intervention needed
CID grade 5
Death
Uncomplicated diarrhea
- Grade 1 or 2 CID
- No complicating s/sx
Complicated diarrhea
- 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
Treatment for uncomplicated diarrhea
- Loperamide
- Oral rehydration
- Diet modifications
- Withhold chemo for grade 2
Tx for complicated diarrhea
- Admit to hosp
- Withhold chemo
- IV fluids & antibiotics
- Octreotide
MOA of loperamide
opioid that inhibits smooth-muscle contraction of intestine to decrease motility (primary neurotransmitter is acetylcholine)
MOA for octreotide
Causes decreased hormone secretion, which increases transit time within intestine, decreases secretion of fluid, and increases absorption of fluid and electrolytes
Octreotide is beneficial for patients with ____ and ____-induced CID
5-FU; irinotecan
Dosing for octreotide
SQ 100-150mcg TDS OR
IV 25-50mcg/hour
Max 500mcg TDS
Up to 10% of patients experience ___-induced lactose intolerance due to lose of lactase activity (temporary)
5-FU
Irinotecan is converted primarily in the liver to active metabolite ___ which is responsible for causing diarrhea
SN-38
SN-38 is deactivated by glucuronidation via ____ to ____
UDP-GT1A1; SN38-G
What gene causes decr expression of UGT1A1
Homozygous for UGT1A1*28
How is SN38-G reactivated back to form SN-38
Bacteria found in gut produce β-glucuronidases which reactivate SN38-G via deconjugation
Mean sx duration for iritotecan-induced diarrhea
30 mins
MOA of irinotecan
Irinotecan is a selective, reversible inhibitor of acetylcholine esterase leading to a cholinergic response
Tx for irinotecan-induced diarrhea in EARLY onset
SQ/IV atropine 0.25–1 mg (maximum 1.2 mg); usually SQ
MOA for atropine
inhibits acetylcholine at muscarinic receptor as a competitive antagonist
Late onset of irinotecan-induced diarrhea for weekly dosing
11 days
Late onset of irinotecan-induced diarrhea for every 3 weeks dosing
6 days
Tx for irinotecan-induced diarrhea in LATE onset
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
Which grp of patients are NOT suited to use enema/ suppositories for constipation
- Low WBC/ platelet
- Immunocompromised
Due to risk of infection/ bleeding
