25. Management of Chemotherapy Toxicities Flashcards
(54 cards)
this type of nausea/vomiting occurs despite prophylactic treatment and/or requires rescue
breakthrough nausea/vomiting
this type of nausea/vomiting occurs during subsequent cycles when antiemetic prophylaxis and/or rescue have failed in earlier cycles
refractory nausea/vomiting
explain the pathophysiology of acute CINV
in acute CINV, free radicals from toxic chemo stimulate the enterochromaffin cells in the GI tract, causing the release of serotonin. serotonin then binds to intestinal vagal afferent nerves via 5-HT3 receptors which trigger the chemoreceptor trigger zone in the CNS
explain the pathophysiology of delayed CINV
substance P is the primary transmitter involved in delayed CINV. chemo drugs trigger the release of substance P from neurons in the central and peripheral nervous systems, which then binds to NKI receptors to induce vomiting
this type of CINV is very amendable to drug therapy. the primary mediator is serotonin and occurs within 24 hours of chemotherapy
acute
this type of CINV has a variable response to drug therapy. the mechanism is not fully understood and occurs after 24 hours to up to one week after chemotherapy
delayed
this type of CINV occurs before patients receive their chemotherapy, after a prior negative experience with chemotherapy (nausea > vomiting)
anticipatory
what are some treatment-specific risk factors for N/V
- emetogenicity of chemo agent
- tumor burden
- combo of chemo agents
- combined modality therapy
- rapid infusion rate
- repetitive daily doses
what are some patient-specific risk factors for N/V
- children > adults
- women > adults
- alcohol history
- hx of morning sickness
- hx of motion sickness
- prior CINV
- depression and anxiety
what are some clinical consequences of CINV
- metabolic derangements
- nutritional depletion and anorexia
- deterioration of patients physical and mental status
- degeneration of self-care and functional ability
- d/c therapy***
these agents can be given as a single dose prior to chemo.
- be careful with Qt prolongation
5HT3 antagonists (e.g. Ondansetron)
this newer agent has a strong binding affinity for 5HT3 with a long plasma half-life of 40 hours therefore effective in both acute and delayed CINV
Palonosetron
what agent should always be given with a 5-HT3 antagonist before chemotherapy
dexamethasone
true or false: if a patient is getting Palonosetron instead of another 5HT3 antagonist, their dose of dexamethasone would need to be increased
false - Palonosetron is dexamethasone sparing therefore can cut back on doses of dexamethasone with this agent
list the NK1 receptor antagonsits
- Aprepitant
- Fosaprepitant
- Netupitant
what CYP enzymes to Aprepitant/Fosaprepitant/Netupitant induce or inhibit
- moderate inhibitor of CYP3A4 (therefore if administered with dexamethasone, decrease dex dose by 50%)
- weak inducer of CYP2C9 (can affect warfarin)
this is a second generation AP that blocks 5HT2 receptors and D2 receptors and may be partially useful for the prevention of acute and delayed CINV (preferred for breakthrough CINV?)
olanzapine
if a patient is on an HEC chemo drug, what agents should be given pre-chemo for nausea?
- dexamethasone 8-12 mg PO
- NK1
- 5HT3 antagonist
if a patient is on a HEC chemo drug, what agents should be given post-chemo for nausea?
- dexamethasone 4 mg PO the evening of chemo then BID for 2-4 days
- +/- prochlorperazine or metoclopramide as needed
if a patient is on an MEC chemo drug, what agents should be given pre-chemo for nausea?
- dexamethasone 8-12 mg PO
- 5HT3 antagonist
if a patient is on an MEC chemo drug, what agents should be given post-chemo for nausea?
- dexamethasone 4 mg PO the evening of chemo then BID for 2-3 days
- +/- prochlorperazine or metoclopramide as needed
if a patient is on a low emetogenicity chemo drug, what agents should be given for nausea?
maybe something pre-chemo and maybe something post-chemo
what are the 3 steps for managing a treatment failure
- rule out and treat other causes of n/v (e.g. medications, infection, gastritis, vestibular dysfunction)
- control this episode of n/v (give additional antiemetic from a diff class, use rectal or iv if pt is vomiting, consider around the clock dosing rather than prn, monitor hydration and electrolytes)
- plan prophylactic regimen for next cycle
- anticipatory: lorazepam the evening before and the morning of chemo
- ensure further anti-emetics cover the full period of delayed nausea (cover how long they were sick for + 24 hrs)
- consider the addition of an NK1 antagonist if not already added
- could also try olanzapine?
what side effects are expected of the following anti-emetic:
metoclopramide
EPS
