Chemotherapy Induced Nausea/Vomiting (3) Flashcards
Impact of CINV
Decrease in…
-nutrition and weight
-physical and mental health
-desire to continue chemotherapy
-quality of life
Increase in…
-medical complications
-dehydration
-electrolyte imbalances
-cost of medical care
Acute vs delayed CINV
Acute = n/v that occurs within the first 24 hours after chemotherapy
Delayed = n/v that occurs after the first 24 hours after chemotherapy
-can last up to 7 days after chemo
Anticipatory CINV
N/v that is a learned reflex or psychological response that occurs before chemotherapy
-can be triggered by sights/sounds/smells/tastes/thoughts
-often occurs due to poor n/v control in previous chemo cycles (so patients get anxious that it will happen again - because they are anticipating that it will happen)
Breakthrough CINV
This is n/v that occurs AFTER chemotherapy despite proper prophylaxis
Because of this patients may require “rescue medications” (that they can use prn)
Refractory CINV
This is n/v that occurs during subsequent cycles despite optimized antiemetic prophylaxis
-we continue to add on agents (use multiple agents with multiple MOAs)
-important to tell patients that medications will probably not eliminate n/v but just limit it
Which pathways/centers lead to n/v when stimulated
High Centers
(5HT3, NK1, D2, GABA)
-from memory, fear, dread, anticipation
Cerebellum
(M, H1)
-inner ear
Chemoreceptor trigger zone
(5HT3, D2, M, CB, opioid)
-blood bone emetics
Solitary Tract Nucleus
(5HT3, NK1, D2, M, H, CB)
When all these are triggered - leads to vomiting center stimulation in the medulla (NK1)
What factors contribute to the overall emetic risk? (2)
Regimen risk factors (how severely emetogenic the specific medications are)
Patient Risk Factors
(Regimen Risk + Patient Risk = Overall Emetic Risk)
What are patient specific factors that increase emetic risk? (5)
- Anxiety/anticipation of nausea (leads to anticipatory n/v)
- Female gender
- YOUNGER age (<50 yo)
- History of motion sickness
- History of pregnancy induced n/v
Which patient specific factor DECREASES emetic risk?
History of alcohol use (> 5 drinks per day) - this decreases risk of developing CINV
Which regimen factors increase emetic risk? (6)
- High emetic risk agent
- Moderate/high dose
- More frequent
- Longer duration
- Short infusion rate
- Radiation - higher amounts of irradiated tissue
IV chemo agents emetic risk categories (4)
Minimal emetic risk
- < 10% frequency of emesis (meaning they have n/v for less than 10% of the time)
Low emetic risk
-10-30% frequency of emesis
Moderate emetic risk
-30-90% frequency of emesis
High emetic risk
- > 90% frequency of emesis
Which IV chemo agents are considered to have minimal emetic risk? (2)
Monoclonal antibodies
Vinca alkaloids (vincristine, vinblastine, vinorelbine)
Which IV chemo agents are considered to have low emetic risk? (2)
Taxanes (paclitaxel and docetaxel)
5-Fluorourical
Which IV chemo agents are considered to have moderate emetic risk? (3)
Carboplatin
Oxaliplatin
Anthracyclines (doxorubicin)
Which IV chemo agents are considered to have high emetic risk? (2)
Cisplatin
Anthracyclines (doxorubicin) - when used in combination with cyclophosphamide
Oral chemotherapy emetic risk categories
Unlike the IV agents (which are broken up into minimal, low, moderate, or high emetic risk) - the oral agents are only broken up into 2 categories …
- Minimal to low emetic risk
- < 30% frequency of emesis - Moderate to high emetic risk
- 30% frequency of emesis or greater
Which oral chemo agents are considered minimal/low risk? (3)
Prophylaxis consideration for these
Capecitabine
Tyrosine kinase inhibitors
Methotrexate
PRN drug therapy (no prophylaxis recommended)
Which oral chemo agents are considered moderate/high risk? (2)
Prophylaxis consideration for these
Etoposide
Lomustine
Prophylaxis IS recommended
Emetic risk categories of radiation
The larger the surface area exposed to radiation –> the higher the emetic potential
- Mild Emetogenic
-radiation to head and neck or extremities (smaller area) - Moderately Emetogenic
-radiation to upper abdomen or pelvis or craniospinal - Highly Emetogenic
-total body irradiation, total nodal irradiation, upper half of body radiation (lots of receptors are in the upper half of the body from the gut to the brain)
How many days should prophylaxis be given for IV chemotherapy?
It depends on the emetic risk of the therapy…
High risk (> 90%) = 4 days
Moderate risk (30-90%) = 3 days
Low risk (10-30%) = 1 day
Minimal risk (< 10%) = no prophylaxis (just prn medications)
Barriers to CINV treatment
Patients may think n/v is just part of their treatment that they have to deal with or they may not want to seem weak so they don’t bring it up - so it’s important to ask patients about this
Patients may fear additional medications (side effects, costs)
Patients may fear that if they bring up these symptoms their provider will stop/lessen their chemotherapy
Non-pharmacologic approaches
Relaxation
Biofeedback therapy
Self-hypnosis
Dietary changes (avoid spicy or high fat foods)
Acupuncture
What are the classes of medications that can be used for CINV? (8)
- Neurokinin-1 Receptor Antagonists (NK1 RAs)
- 5-Seretonin Receptor Antagonists (5HT3 RAs)
- Corticosteroids
- Dopamine antagonists
- Atypical antipsychotics
- Benzodiazepines
- Cannabinoid receptor agonists
- Acid suppressing agents
5HT3 RA mechanism
Inhibits central and peripheral 5HT3 (serotonin) receptors
What are 5HT3 RAs indicated for in CINV?
Prevention of acute and delayed CINV for low to high emetogenic chemotherapy
(so basically gold standard for all severities prophylaxis)
Which medications are 5HT3-RAs (4)
Ondansetron (most popular)
Granisetron
Palonosetron
Dolasetron
5HT3 RA main ADR
QTC prolongation (dose related)
-monitor, especially if patient has cardiac issues
Which 5HT3 RA comes in a patch?
Granisetron (and it also comes in an ER SQ injection)
This is helpful for preventing delayed n/v, especially useful if patients don’t want to take anything by mouth
Which 5HT3-RA has a long half life?
Palonosetron
-half life is about 40 hours
(useful in regimens, we only have to give this once and it lasts long)
5HT3 RA formulations
Ondansetron - IV and PO
Granisetron - IV, PO, ER SQ, patch
Palonosetron - IV only
Dolasetron - PO only
NK1 RA MOA
Inhibit the substance P/neurokinin 1 receptor
NK1 RA indication for CINV
Prevention of acute and delayed CINV for moderate-high emetogenic chemotherapy
Which medications are NK1 RAs? (3)
Aprepitant
Fosaprepitant
Rolapitant
NK1 RA formulations
Aprepitant = PO
Fosaprepitant = IV
Rolapitant = PO (no used much)
What are the 2 combination NK1 RA/5HT3 RA products and their formulations/administration
netupitant/palonosetron = PO
fosnetupitant/palonosetron = IV
NK1 RA drug interaction consideration
NK1 RAs are CYP3A4 inhibitors - so specifically this will interact with dexamethasone and increase its concentrations (and they are often used together for CINV)
So if using together - decrease the dose of dexamethasone
(Rolapitant specifically is a CYP2D6 inhibitor and CYP3A4 substrate- check for drug interaction)
Which NK1 RA can be given beyond day 1?
Aprepitant only
-if aprepitant is started on day 1, it can be continued
-but if any of the other agents were started on day 1 that is it - can’t give those on the next day and cannot use aprepitant after
Corticosteroid MOA for CINV
Act centrally; work synergistically to increase effectiveness of other CINV agents
Corticosteroid indication for CINV
prevention of acute and delayed CINV in low-high emetogenic chemotherapy
Which corticosteroid is used for CINV?
Dexamethasone
Corticosteroid ADRs and considerations
Insomnia, GI upset, dyspepsia, agitation, weight gain, hyperglycemia
-can consider acid suppressing therapy addition to help with dyspepsia
-dose in the morning to minimize insomnia
-we generally are using for a short period of time though so long term side effects are not seen
-still, should be cautioned in patients with diabetes, elderly, or psychiatric history
(consider steroid sparing regimen)
Dexamethasone formulation
IV or PO
Dexamethasone has a DDI with which drug class used for CINV?
NK1 RAs - they will increase the level of dexamethasone (CYP3A4 inhibitors)
So, dexamethasone dose should be decreased if being used together
Dopamine antagonist MOA
blocks dopaminergic receptors in the brain
Dopamine antagonist indication for CINV
Used for breakthrough treatment (prn)
And prevention of low emetogenic chemotherapy
Which medications are dopamine antagonists? (3)
Prochlorperazine
Metoclopramide
Haloperidol (more potent and more side effects- not typically used)
Dopamine antagonist 2 BBWs
- Increased risk of death in elderly patients with dementia related psychosis
- Tardive dyskinesia (often irreversible)
Dopamine antagonist ADRs
Sedation, hypotension, anticholinergic effects, dystonia’s, extrapyramidal symptoms
QTc prolongation
neutropenia (which may already be occurring because of cancer treatment)
Lots of side effects for these so we don’t really use them unless we have to (which is why they often only added for breakthrough treatment)
What screening needs to be done before using prochlorperazine?
ANC
do not use if ANC < 1000
Metoclopramide should be used at __________ doses to…
Should be used at LOW doses to avoid extrapyramidal symptoms
At higher doses it inhibits serotonin
Dopamine antagonist formulations
Prochlorperazine = PO, IV, IM
Metoclopramide = PO only
Haloperidol = PO/IV
Atypical antipsychotic MOA
blocks multiple neurotransmitters - dopamine, serotonin, histamine, acetylcholine
Which atypical antipsychotic is the only one approved for CINV?
Olanzapine
Olanzapine indication for CINV
prevention of acute and delayed CINV in moderately to highly emetogenic chemotherapy
or for breakthrough CINV
Olanzapine ADRs
Drowsiness, dizziness, orthostatic hypotension
-patient should start with taking this in the evening, sedation should improve over time
hyperglycemia, weight gain
EPS
QTc prolongation
Lots of side effects but it works really well, so we still use it
Olanzapine formulation
PO only
Olanzapine BBW
increased risk of death in elderly patients with dementia related psychosis
Cannabinoid receptor agonist indication for CINV
Used for prophylaxis if refractory to other antiemetics
Cannabinoid drugs and formulation
Dronabinol (PO)
Nabilone (PO)
Cannabinoid ADRs
Dizziness, somnolence
Increased appetite (this may be beneficial for some patients who struggle with this)
Withdrawal symptoms of abrupt discontinuation after continuous use
Benzodiazepine indication for CINV
Used for anticipatory CINV
Which benzodiazepines are used for CINV and what are their formulations?
Alprazolam (PO)
Lorazepam (PO, IV, SL)
Benzodiazepine ADRs
Sedation
Dizziness
Disorientation
Acid suppressing agent indication for CINV
Added for prophylaxes of CINV if patients have underlying GERD, heartburn, or dyspepsia
Which 2 classes of acid suppressing agents are used for CINV and which formulations?
Histamine 2 receptor antagonists (PO)
Proton pump inhibitors (PO)
