IC5 Flashcards
(64 cards)
1
Q
Describe the peripheral pathway of CINV
A
- Peripheral pathway responsible for acute CINV
- The GIT since it has fast reproducing cells
- Chemotherapy kills these fast reproducing cells
- Serotonin release causing CINV
2
Q
Describe the central pathway of CINV
A
- Central pathway responsible for delayed CINV
- CNS along with chemoreceptor trigger zone
- NK1 release causing CINV
3
Q
Acute CINV
A
- Starts 1-2h after administration
- Peaks at 5-6h
- Resolves at 12-24h
4
Q
Delayed CINV
A
- Peaks at 48-72h
- Resolves in 1-3 days
5
Q
Breakthrough CINV
A
CINV occurs despite preventive therapy
6
Q
Anticipatory CINV
A
Uncontrolled emesia prior to chemotherapy
7
Q
Refractory CINV
A
Antiemetic prophylaxis or rescue therapy has failed in previous cycles
8
Q
Risk factors for CINV
A
- Age < 50 years
- Female
- History of low prior alcohol intake, patient is not a chronic drinker: < 1 glass per day
- History of previous chemotherapy induced emesis, vomited with chemo drugs
- History of motion sickness
- History of emesis past pregnancy
- Anxiety
9
Q
High emetogenic risk drug combination
A
NK1 (day 1) + 5HT3 (day 1) + Dexa (day 1-4) +/- Olanzapine (day 1-4)
10
Q
Moderate emetogenic risk drug combination
A
5HT3 (day 1) + Dexa (day 1-3)
11
Q
Low emetogenic risk drug combination
A
5HT3 or Dexa or Dopamine antagonist (all day 1 only)
12
Q
NK1 antagonist indication
A
Acute and delayed CINV
13
Q
Examples of NK1
A
Aprepitant PO 125mg OD day 1, 80mg OD day 2 and 3 (3 day course)
Akynzeo: PO Netupitant 300mg + Palonosetron 0.5mg OD day 1 (NK1+5HT3)
14
Q
ADR of NK1 antagonist
A
Fatigue, weakness, nausea, hiccups
15
Q
DDI of NK1 antagonists
A
NK1 antagonists are CYP3A4 inhibitors
- Steroids, warfarin, benzodiazepines, ifosfamide
16
Q
5HT3 antagonist indication
A
Acute CINV only
17
Q
Examples of 5HT3 antagonist
A
Ondansetron PO/IV 8-16mg OD day 1, 8mg OD day 2 onwards
Granisetron PO/IV 1mg OD day 1, 1mg OM day 2 onwards
18
Q
ADR of 5HT3 antagonist
A
QTC prolongation (black box)
Headache, constipation
19
Q
Dexamethasone indication
A
Acute and delayed CINV
20
Q
Examples of dexamethasone
A
Dexamethasone PO/IV 12mg OD day 1, 8mg OD day 2 onwards
21
Q
ADR of dexamethasone
A
Elevation of blood glucose
Insomnia, anxiety, GI upset
Psychosis, reactivation of ulcers
22
Q
Olanzapine indication
A
Acute and delayed CINV
23
Q
Examples of olanzapine
A
Olanzapine PO 5-10mg OD
Elderly: 2.5mg OD
24
Q
ADR of olanzapine
A
Fatigue, sedation, postural hypotension, anticholinergic side effects (dry mouth, blurred vision, urinary retention)
25
Metoclopramide indication
Acute and breakthrough CINV
26
Example of metoclopramide
Metoclopramide PO/IV 10mg OD-TDS prn
27
ADR of metoclopramide
Sedation, diarrhoea, EPSE – akathisia, dystonia
28
DDI of metoclopramide
Metoclopramide + Olanzapine = increased risk of EPSE – tardive dyskinesias, neuroleptic malignant syndrome
29
Benzodiazepines indications
Anticipatory CINV
30
Example of benzodiazepines
PO Alprazolam 0.5mg-1mg night before treatment + 1-2h before chemotherapy
PO Lorazepam 0.5mg-2mg night before treatment + 1-2h before chemotherapy
31
ADR of benzodiazepines
Drowsiness, dizziness, hypotension, anterograde amnesia – cannot form new memories, paradoxical reactions – hyperactiveness, aggression
32
Non-pharmacological management of anticipatory CINV
- Relaxation, music therapy
- Hypnosis, guided imagery
- Systematic desensitisation
33
Adjunctive agents indication
Refractory CINV
34
Examples of adjunctive agents
Haloperidol (Butyrophenones)
Dose: PO/IV 0.5-2mg q4-6h
ADR: EPSE, sedation
Prochlorperazine, chlorpromazine, promethazine (Phenothiazines)
Dose: PO Prochlorperazine 10mg TDS/QDS prn
ADR: drowsiness, hypotension, EPSE
35
Non-pharmacological management of CINV
- Take small, frequent meals, avoid heavy meals
- Avoid greasy, spicy, very sweet or salty food or foods with strong flavours or smells
- Sip small amounts of fluid often instead of drinking a full glass at one time
- Avoid caffeine containing drinks or foods
- Avoid lying flat for 2h after eating
- Suck on lemon drops
36
Management of breakthrough CINV
- Add on agent from different drug class different MOA
- If PO route not feasible due to vomiting, use IV route
- Hydration and fluid repletion for losses
- Reassess next cycle’s antiemetics for appropriateness
37
Risk factors for CID
- Age > 65 years
- Female
- Eastern Cooperative Oncology Group (ECOG) performance status of at least 2
- Bowel inflammation or malabsorption
- Bowel malignancy
- Biliary obstruction
- First cycle of chemotherapy
- Cycle duration of greater than 3 weeks
- Neutropenia, anaemia
- Mucositis
- Vomiting, anorexia
38
Grade 1 CID
Increase in loose stools < 4 times a day above baseline
39
Grade 2 CID
Increase in loose stools 4-6 times a day above baseline
Limiting activities of daily living
40
Grade 3 CID
Increase in 7 or more stools per day above baseline
Limiting self care
Hospitalisation needed
41
Grade 4 CID
Life threatening, urgent intervention needed
42
Grade 5
Death
43
Uncomplicated CID
Grade 1 or 2
No complicating signs and symptoms
44
Complicated CID
Grade 3 or 4
OR
Grade 1 or 2 with at least 1:
- Cramping
- > grade 2 n/v
- Decreased performance status
- Fever
- Sepsis
- Neutropenia
- Frank bleeding: fresh bleed
- Dehydration
45
Goals of therapy for CID
- Improve recovery of intestinal mucosa
- Improve QOL and ADL
- Decrease morbidity and mortality from CID
- Decrease hospitalisation
46
Pharmacological management of uncomplicated CID
Diarrhoea lasting <12h
- PO Loperamide 4mg, then 2mg q4h or after every episode, max 16mg per day
- Continue until 12h free of diarrhoea then stop
- If patient cannot tolerate/swallow loperamide, can use diphenoylate/atropine
Diarrhoea lasting >12-24h
- PO Loperamide 2mg q2h
- PO Antibiotics for infection prevention
- Start octreotide or other second line agent
47
Pharmacological management of complicated CID
- SQ Octreotide 100-150mcg TDS
- Or IV Octreotide with dose escalation up to 500mcg TDS
- IV fluid hydration
- IV antibiotics: Ciprofloxacin x 7 days
48
MOA of irinotecan induced diarrhoea
- Irinotecan converted to SN38 (active metabolite) which is very cytotoxic, responsible for diarrhoea
- SN38 deactivated by glucuronidation to SN38-G (inactive metabolite) by UDP-GT 1A1 in liver
- Presence of irinotecan alters commensal bacteria in gut
- Bacteria in gut produce beta glucuronidases
o Reactivate SN38G SN38 via deconjugation
o SN38 damages gut mucosa during excretion
- Leads to ablation of crypts, villus blunting, atrophy of epithelium in small and large intestine
49
Pharmacogenomics of irinotecan induced CID
- SN38 deactivated by glucuronidation to SN38-G by UDP-GT 1A1
- Homozygous for UGT1A1*28 decreased expression of UDP-GT 1A1 increased toxicity, more diarrhoea
50
Pharmacological management of irinotecan induced diarrhoea
Acute onset < 24h
- SC/IV Atropine 0.25-1mg (Max 1.2mg) – usually SC
- Indication: acute onset irinotecan induced diarrhoea
- MOA: Atropine is a competitive antagonist which inhibits acetylcholine at muscarinic receptors
- ADR:
o Insomnia, dizziness
o Tachycardia, blurred vision, dry mouth
o Constipation
- Contraindicated in glaucoma
Late onset
- PO Loperamide 4mg after first diarrhoea, then 2mg every 2h, no max dose (special dosing)
o Dose 4mg every 4h so patient don’t have to keep waking up
o Stop when 12h passes without any bowel movement
51
ADR of loperamide
- Constipation, abdominal pain, dizziness, rash, bloating, nausea and vomiting, dry mouth, drowsiness
- High doses associated with paralytic ileus (muscles and nerves of intestine stop working)
52
ADR of octreotide
- Bradycardia, arrhythmias
- n/v/c
- Headache, dizziness
- Enlarged thyroid
53
Non-pharmacological management of CID
- Probiotics with Lactobacillus prevent CID
- Diet modification
o Avoid
o Caffeine, alcohol, fruit juice,
o Lactose containing foods at least 1 week after CID resolved loss of lactase activity
o Spicy foods
o High in fat or fiber
o Dietary supplements with high osmolarity
- Have small frequent meals
- Bananas, rice, applesauce, toast (BRAT) diet
- Take at least 3L of clear fluids containing salt, sugar and electrolytes
54
Risk factors for constipation
- Lowered fluid intake, dehydration
- Loss of appetite, anorexia
- Lack of fibre or bulk forming foods in diet
- Iron, calcium supplements
- Low physical activity, bed rest
- Overuse of laxatives
- Thyroid problems, depression
- High Ca or K in blood
- Cancer in large intestine or pressing on spinal cord\
- Medication induced
o Pain relief: morphine, codeine
o Chemotherapy: Vincristine, vinblastine, vinorelbine
o Antiemetics: Ondansetron, granisetron, anticonvulsant drugs
55
Prevention of constipation
- Eat more fibre: soluble and insoluble fibre
- Eat natural laxatives: prunes, fruits with high fibre
- Increase physical activity gradually since chemo makes patient tired
56
Pharmacological management of constipation
- Stool softeners
- Laxatives
* Stimulate bowel activity: Senna 15mg ON, lactulose 10mg TDS, mineral oil
* Increase fibre or produce bulk: Psyllium, PEG (forlax, fybogel) 1 sachet BD
- Enemas
* Fleet (phosphate), tap water
- Suppository
* Glycerine, bisacodyl
- Enemas and suppository not recommended when WBC or platelet count low due to risk of infection or bleeding
- Only use enemas or suppositories if constipation is very bad
57
Grade 1 mucositis
Mild, no intervention
58
Grade 2 mucositis
Moderate pain, modified diet
59
Grade 3 mucositis
Severe pain, interferes with PO intake
60
Patient related risk factors for mucositis
- Autoimmune disorders
- Diabetes
- Female for 5FU
- Caucasians > African American
- Genetic predisposition to tissue damage: deficiency in enzymes responsible fro metabolising chemotherapy
- Folic acid or vitamin B12 deficiency
61
Treatment related risk factors for mucositis
- Varies by agent and regimen
- S-phase specific agents have highest risk
- Duration, dose intensity, schedule
- Prolonged or repetitive lower doses higher risk > bolus doses.
- Risk increases with number of cycles
- Risk increases when clearance of chemotherapy is delayed by renal or hepatic impairment
- Previous therapies toxic to mucosa
- Risk increases with previous episodes of mucositis
- Radiation added on to chemotherapy
- Dependent on radiation source, dosage, dose intensity and volume of mucosa irradiated
- Smoking
- Alcohol consumption
- Xerostomia and infection
62
Prevention of mucositis
- Oral cryotherapy: suck on ice chips
* Vasoconstriction so chemo drug doesn’t go to mucosa and cause mucositis
- IV Palifermin 60mcg/kg/day x 3 days
* Reduces severity and duration of oral mucositis
* Extremely costly
- Benzydamine HCL
- Good oral hygiene: use a soft toothbrush, gargle with salt water after each use
- Laser therapy after radiation: not done in SG
63
Pharmacological management of mucositis
- Oracare suspension
- Mylocaine suspension
- Morphine sulfate solution
- Oracort E paste
- Soragel
- Medijel
- Difflam gargle/soray: benzydamine
64
Non-pharmacological management of mucositis
Alcohol free mouthwashes
- Oral7 mouthwash
- BioXtra mouthwash
Do not use alcohol containing mouthwash due to the drying effect
