chemo Flashcards
(65 cards)
1
Q
2 emesis pathways
A
central - delayed CINV
peripheral - acute CINV
2
Q
types of CINV (5)
A
- acute - starts 1-2h after admin
- delayed - starts 48-72h after
- breakthrough - despite preventive tx
- anticipatory - uncontrolled emesis b4 chemo
- refractory - despite antiemetic tx in prev cycles
3
Q
3 steps to choose antiemetic regimens
A
- emetic risk of each chemo drug
- assess pt risk factor for CINV
- choose regimen that can cover drug w highest emetic risk
4
Q
pt risk factors for CINV (7)
A
- young (<50)
- female
- hx of low prior alcohol intake
- hx of chemo induced emesis
- hx of emesis during pregnancy
- motion sickness
- anxiety
5
Q
anti-emetic regimen for high risk
A
Day 1: NK1 + 5-HT3 + Dexa +/- Olanzapine
Day 2-4: Dexa / Ola
6
Q
anti-emetic regimen for medium risk
A
Day 1: 5HT3 + Dexa
Day 2-3: Dexa
7
Q
anti-emetic regimen for low risk
A
Day 1: 5HT3/Dexa/Dopa
8
Q
MOA of NK1 antagonists
A
binds to neurokinin receptors, preventing substance P binding –> attenuate vagal afferent signals
9
Q
SEs of NK1
A
fatigue, weakness, nausea, hiccups
10
Q
Dose of NK1s
A
Aprepitant (Emend): 240mg OD on day 1 + 80mg OD on day 2-3
Netupitant 300mg + Palonosetron 0.5mg (Akynzeo): on Day 1
11
Q
DDIs of NK1
A
steroid
warfarin
BZDs - decreased metabolism
ifosfamide - decreased metabolism
12
Q
emend vs akynzeo
A
emend is cheaper
akynzeo is more convenient
13
Q
what type of CINVs does NK1 treat
A
acute, delayed
14
Q
what type of CINVs does dexamethasone treat
A
acute, delayed
15
Q
what type of CINVs does 5HT3 treat
A
acute
16
Q
what type of CINVs does olanzapine treat
A
acute, delayed
17
Q
what type of CINVs does dopamine antagonists treat
A
acute (in low emetogenic), breakthrough
18
Q
what type of CINVs does BZD treat
A
anticipatory
19
Q
what type of CINVs does adjunctive agents treat
A
refractory
20
Q
MOA of 5HT3 antagonists
A
block HT3 receptors peripherally in GIT and centrally in medulla
21
Q
SEs of 5HT3
A
headachen, constipation
BLACK BOX WARNING: QTc prolongation
22
Q
Doses of 5HT3
A
Ondasetron: 8-16mg OD (D1) + 8mg BD (D2 onwards) [max: 16mg/day]
Granisetron: 1mg OD (D1) + 1mg OM (D2 onwards)
23
Q
Doses of dexamethasone
A
D1: 12mg OD
D2 onwards: 8mg OD
24
Q
Routes for main antiemetic drugs
A
all except NK1 is PO/IV
25
SEs of dexamethasone
(most common) transient elevations in glucose, insomnia, stomach upset --> take after food
(less common) psychosis, reactivation of ulcers
26
MOA of olanzapine
atypical antipsychotic: antagonise dopamine, serotonin, histamine, cholinergic receptors
27
SEs of olanzapine
anticholinergic, sedation, postural hypotension
28
Dose of olanzapine
5-10mg OD
elderly: 2.5mg OD
29
MOA of dopamine antagonists (metoclopramide)
peripherally --> block dopamine receptors in chemoreceptor trigger zone, incr gut motility
29
SEs of dopamine antagonists
mild sedation, diarrhea, EPSE
30
dose of metoclopramide
10mg TDS prn
31
what cannot be used together with metoclopramide (CINV)
olanzapine --> incr EPSE risk
32
MOA of BZD
binds to BZD receptors on postsynaptic GABA receptors to incr inhibitory effects of GABA
33
dose of BZD
PO alprazolam 0.5-1mg
PO lorazepam 0.5-2mg (take night before treatment + 2-3h before treatment)
34
SEs of BZD
drowsiness, dizziness, incr risk of falls in elderly
35
adjunctive agents in CINV
1. butyrophenones (haloperidol): PO/IV 0.5-2mg q4-6h
2. phenothiazines (prochlorperazine): 10mg TDS/QDS PRN
36
principles for breakthrough CINV
try another agent, rmb to hydrate pt if vomiting, reassess next cycle's antiemetics to ensure regimen is appropriate
37
targeted therapies that can cause CID
tyrosinase kinase inhibitor - dose dependent
EGFR inhibitor - occur within 2-3d of therapy, neratinib req prophylaxis with loperamide for 1st 2 cycles
37
non-pharm for CINV (4)
small, freq meals
avoid foods with strong flavors (spicy, sweet/salty)
avoid caffeinated beverages
avoid lying flat for 2h after
38
treatment specific risk factors for CID (2)
1st cycle of chemo
chemo cycle duration >3w
38
pt risk factors for CID (7)
age>65 yo
female
ECOG performance status at least 2
bowel inflammation/malabsorption
bowel malignancy
bile obstruction
pt has other sx (mucositis, vomiting, anorexia, anemia)
39
CTCAE severity grading for CID
(count by increase above baseline)
g1: <4 stools
g2: 4-6 stools + limiting daily activity
g3: 7 and more + hospitalisation
g4: life threatening
g5: death
40
uncomplicated CID
grade 1, 2
40
complicated CID
grade 3-5
grade 1, 2 + other sx (cramp/NV/fever/sepsis/neutropenia/frank bleeding/dehydration)
41
pathophysiology of CID
caused by direct damage and inflammation to intestinal mucosa --> imbalance btwn absorption and secretion
42
treatment for uncomplicated CID (non-pharm + pharm)
- diet modification
- oral hydration (8-10 glasses)
- cease chemo if grade 2
- PO loperamide 4mg at first, 2mg for every ep after until 12h free of diarrhea
42
diff outcomes after treating with loperamide for uncomplicated CID (3)
if diarrhea is improving after 12-24h, start solid food slowly
if diarrhea persists after 12-24h, loperamide 2mg q2h + oral Abx
if diarrhea persists as uncomplicated 12-24h after loperamide, begin octreotide
43
Treatment for complicated CID
- admit to hospital + withhold chemo
- administer octreotide
- IV fluids
- IV abx (cipro)
44
Doses of octreotide for complicated CID (2)
SC octreotide 100-150mcg TFS
IV octreotide 500mcg TDS
45
non-pharm for CID (7)
- probiotics with lactobacillus
- avoid caffeine, alcohol, fruit juice that contain lactose
- avoid foods spicy or high in fat or fibre
- avoid diet supplements with high osmolarity
- avoid lactose-containing food for at least 1w after
- BRAT
- more than 3L of clear fluids containing salt and sugar
45
MOA of octreotide + SE
MOA: decrease hormone secretion to increase GI transit time
SE: bradycardia, arrhythmia, abdominal pain, NV, enlarged thyroid
46
Irinotecan-associated diarrhea physiology
irinotecan is converted to SN-38 in liver (100-1000 times more cytotoxic than parent)
SN-38 gets deactivated into SN28-G by glucuronidation via UDP-GT 1A1 --> reactivated by beta-glucuronidases secreted by gut bacteria
Hence, causes ablation of crypts, villus blunting, atrophy of epithelium
47
Treatment of irinotecan assoc diarrhea
(early: <24h of irinotecan)
SC/IV atropine 0.25-1mg (max 1.2mg) - CI in glaucoma
(late: >24h) PO loperamide 4mg after 1st loose bowel --> 2mg q2h (or 4mg q4h at night) until 12h free of diarrhea
48
risk factors for constipation (10)
● Lowered fluid intake & dehydration
● Loss of appetite (anorexia)
● Lack of fibre or bulk forming food in the diet
● Vitamin or mineral supplements such as Iron / calcium
● Overuse of laxatives
● Lower level of physical activities / bed rest
● Thyroid problems
● Depression
● High levels of calcium or potassium in blood
● Cancer growing into large intestine or pressing on spinal cord
48
drug-induced constipation
● Pain-relievers: opioids (morphine, codeine)
● Vinca alkaloids (vincristine, vinblastine or vinorelbine)
● Antiemetics (ondansetron, granisetron) / anticonsulvant
49
prevention of constipation
● Eat more fibre (care for diabetic patients)
● Eat natural laxatives
● Increase physical activity
50
types of laxatives
● Stool softener: hold water + keep it soft
● Laxative (senna, lactulose): promote / stimulate bowel activity / increase fibre or produce bulk → can use together with stool softener
● Enema / suppository: avoid in patient with high risk of bleeding + immunocompromised may introduce germs in and risk infection
51
diff treatments for constipation
● Fybogel 1 sachet BD
● Lactulose 10 mL TDS
● Senna 15 mg ON
● Forlax 1 sachet BD (grapefruit extract flavoring)
52
pathophysiology of mucositis
Damage to mucosa of the oral cavity, pharynx, larynx, esophagus, and GI tract due to cancer therapy
Chemo/radiation causes direct damage to epithelial stem cells --> EGFR play a role in maintaining mucosal integrity (found in esophagus and increased in inflamed mucosa)
52
5 stages of mucositis
1. Initiation: Direct toxicity to cells
2. Upregulation: DNA damage
3. Signaling and Amplification: Positive feedback on cytokines (TNF-a, IL-1B, IL-6) to increase damage
4. Ulceration (most symptomatic phase): Atrophy & mucosal breakdown (7d after treatment)
5. Healing: WBC recovery at day 12-16, proliferation of epithelial cells, return of local flora
53
timeline of mucositis
● Day 0-5: mostly asymptomatic, redness, swelling, burning
● Day 0-7: desquamation, white patches (often mistaken as candidiasis)
● Day 6-12: contiguous pseudomembranes
● Day 7-16: painful erosion, ulceration
54
WHO grading of mucositis
● Grade 0: no evidence
● Grade 1: erythema + soreness
● Grade 2: ulcer + eating solid
● Grade 3: ulcer + requires liquid diet
● Grade 4: ulcer + not being able to take PO
● Grade 5: Death
54
pt risk factors for mucositis (5-6)
● Autoimmune disorder
● Diabetes
● Female / Caucasians
● Genetic predisposition to tissue damage (deficiency in genes)
● Folic acid or vit B12 deficiency
54
treatment for mucositis
● PO Cryotherapy → Sucking on ice (vasoconstriction)
● IV Palifermin 60 mcg/kg/day x 3 days (very expensive)
● Benzydamine HCL mouthwash
● Drink Morphine sulfate 1mg/mL syrup
○ ½-1h before food
● Oracare Suspension (Nystatin 125,000U, Tetracycline 62.5mg, hydrocortisone 5mg, diphenhydramine 11.5mg/10mL)
○ After meals to kill germs
● Mylocaine suspension (diphenhydramine 11.5mg, lignocaine 16.7mg/10mL)
○ Take before meals
● (For ulcers) Oracort-E, Medijel, Soragel, Difflam gargle / spray
● (Artificial saliva) Oral7 mouthwash, BioXtra mouthwash
Avoid alcohol based mouthwash → drying effect (xerostomia)
55
treatment risk factors for mucositis (4)
● Chemotherapy (duration, dosing, schedule)
● Radiation (risk increases w C+R, source, dosage, intensity)
● Smoking & alcohol consumption
● Risk is higher in the presence of xerostomia and infection
