Cancer Tx-Related Tox - N/V Flashcards
Most common AEs of chemotx?
N/V
How should N/V tx be approached?
It should be prevented before it actually happens
What’s acute CINV?
occurs ≤ 24h post-chemo
What’s delayed CINV?
occurs > 24h post-chemo
What’s anticipatory CINV?
Occurs as a conditioned response due to past neg experience BEFORE receiving next tx
What’s breakthrough CINV?
Occurs despite N/V prophylaxis
NTs involved in CINV?
5-HT3, Substance P
How does chemotx-induced release of serotonin bring about CINV?
It causes release of SEROTONIN in the GIT (peripherally) and via vagus nerve stimulation of the vomiting centre (centrally)
How is substance P involved in CINV?
It stimulates NK-1 receptors in the CNS
What type of CINV is usually assoc w/ substance P and its stimulation of NK-1 receptors?
Delayed CINV
How does EtOH intake affect the CTZ?
It makes the CTZ LESS sensitive > less likely to vomit
What is a biphasic pattern of emesis?
When there’s one early and large episode of acute vomiting, then a second prolonged, less intense peak of vomiting
What’s a monophasic pattern of emesis?
When there’s a long interval of moderately intense emesis ~6h post-tx
4 emetic risk gps:
HIGH: risk in > 90% of pts
MOD: risk in 30-90% of pts
LOW: risk in 10-30% of pts
MINIMAL: risk in < 10% of pts
Serotonin receptor (5-HT3) antagonist drugs:
ondansetron, granisetron
MOA of 5-HT3 antagonists
bind to 5-HT receptors in CTZ and in vagal afferent fibres from the upper GIT
How is the efficacy of 5HT3 antagonists usually improved?
by adding a CS (usually dexamethasone)
AEs of 5-HT3 receptor antagonist
h/a, constipation
What kind of emesis is tx’ed by 5-HT3 receptor antagonists?
acute CINV
Risks assoc w/ higher doses of 5-HT3 receptor antagonists?
QT prolongation
Preferrend 5-HT3 receptor antagonist?
Palonosetron (longer half life, single dose, less concern w/ QT prolongation)
MOA of neurokinin-1 (NK-1) receptor antagonists?
blocks substance P from binding to NK-1 receptors in the CNS
When are neurokinin-1 (NK-1) receptor antagonists given?
Day 1 BEFORE chemotx
What should be kept in mind when giving neurokinin-1 (NK-1) receptor antagonists with dexamethasone?
Dexa dose should be reduced 50% due to CYP interactions (CYP3A4 and CYP 2C9)
T or F: The action of neurokinin-1 (NK-1) receptor antagonists is canceled out when given concurrently with 5-HT3 receptor antagonists like ondansetron
F
They work synergistically, actually
neurokinin-1 (NK-1) receptor antagonists can be used for which types of CINV?
Acute and delayed
Wrt CINV, CS monotx is used for…
low emetogenic chemo
Wrt CINV, how are CS’s used for highly emetic and moderately emetic chemo?
CS is combined w/ a 5-HT3 receptor antagonist +/- NK1 receptor antagonist or olanzapine
What kind of CINV is prophylaxed w/ CSs?
acute and delayed CINV
MOA of CS for CINV?
Not sure (perhaps prostaglandin inhibition plays a role)
Steroid of choice for CINV?
Dexamethasone
How’re dopamine antagonists used in CINV?
Mainly for breakthrough CINV
Risk of domperidone (dopamine antagonist)?
QT prolongation
What’s used for preventing anticipatory emesis?
benzos
T or F: BZDs are not great as antiemetics
T
Olanzapine MOA in CINV?
acts on several receptors: DA, 5-HT3, histamine, ACh, and muscarinic
Olanzapine is effective in preventing this.
Delayed N (nausea only)
How is olanzapine used in high and mod emetogenic chemotx?
In combo w/ 5-HT3 receptor antagonist and dexamethasone (+/- NK1 receptor antagonist)
dimenhydrinate MOA
Histamine antagonist
Dimenhydrinate place in tx for CINV?
PRN for acute sx ctrl
Cannabinoids/medical marijuana place in tx for CINV?
Refractory N/V only
Efficacy of cannabinoids in CINV?
Not v. effective
T or F: Immediate antiemetic regimen alteration should take place if breakthrough N/V is occurring
F
Must exclude other dz and med-related causes for emesis first
When should you refer a CINV pt?
prolonged N/V, sig. wt loss, sx’s of dehydration, fever, abdominal pain, blood or “coffee grounds” in vomitus, altered consciousness
Non-pharm approaches for CINV
eat small, freq meals, bland foods (no spicy or acidic foods), calorie-dense foods, eat foods at rm temp
