25. Management of Chemotherapy Toxicities Flashcards
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
what side effects are expected of the following anti-emetic:
prochlorperazine
sedation and hypotension
what side effects are expected of the following anti-emetic:
haloperidol
rarely EPS
what side effects are expected of the following anti-emetic:
ondansetron
constipation and headache
what side effects are expected of the following anti-emetic:
dimenhydrinate
sedation, dry mouth, blurred vision
what side effects are expected of the following anti-emetic:
corticosteroids (dexamethasone)
insomnia, hyperglycaemia, heartburn, mood changes
what side effects are expected of the following anti-emetic:
olanzapine
sedation
what are some complications of diarrhea that we want to avoid through prevention and early/aggressive management
dehydration, electrolyte abnormalities and hypotension
true or false: diarrhea often leads to dose reduction, delay in treatments or treatment discontinuation
true
what are the 3 major mechanisms of chemo-related diarrhea
- increased secretion of electrolytes leading to secretory diarrhea
- increased intraluminal osmotic substances leading to osmotic diarrhea
- altered GI motility
what are some therapy related risk factors for diarrhea
- chemo
- rads
- multi-modailty tx
what are some GI risk factors for diarrhea
- previous GI surgery
- IBD
- lactose intolerance
- nutritional supplements
- dietary fibre
what are some neurologic risk factors for diarrhea
anxiety
what are some medications that may cause diarrhea
- abx
- laxatives and antacids
- misoprostol
- metoclopramide
true or false: prophylactic anti-diarrheal treatment is a standard approach
false
what is the initial management of uncomplicated diarrhea
give standard dose of loperamide
- inital dose of 4 mg then 2 mg q4h after each unformed BM
what should be done if the patient still has persistant diarrhea after 12-24 hours of being on the standard dose of loperamide
increase loperamide to 2 mg q 2 hours (high dose loperamide)
what should be done if the patient still has persistant diarrhea after 12-24 hours of being on high dose loperamide
add octreotide TID
this is a synthetic opioid that binds to mu opiate receptors in the intestinal wall and inhibits peristalsis; this slows GI transit time, allowing more time for absoption of water in the intestine
loperamide
true or false: all doses of loperamide can can Qt prolongation
false - worry when get > 16 mg/day
this anti-diarrheal agent contains a synthetic opioid chemically related to meperidine; it inhibits excessive GI motility
Lomotil (diphenoxylate)
Lomotil contains a subtherapeutic amount of this medication to discourage abuse
atropine
true or false: Lomotil is more effective than loperamide
false - loperamide is more effective, providing more rapid control of diarrhea and prolonging the time to first recurrence of diarrhea
this anti-diarrheal agent is a somatostatin analog that decreases GI peptide secretion, splanchnic blood flow and GI motility and increases water absorption
Octreotide
true or false: Octreotide is more effective than loperamide
true
true or false: Octreotide is an oral agent
false - SC
constipation in cancer patients is usually due to these TWO factors
poor oral intake and drugs (e.g. analgesics or antiemetics - ondansetron)
what are some risk factors for constipation in cancer patients
- opioids
- lack of physical activity / bed rest
- low fiber diet and decreased intake of food
- decreased fluid intake and dehydration
- depression
- chemo drugs
- anti emetics
true or false: enemas and suppositories are first line for constipation in cancer patients to reduce drug interactions
false - DO NOT USE THESE especially if patient is neutropenic
- risk of nicking the skin and alot of bad bugs in that area thus increased risk of infection
true or false: a stimulant laxative is the first line for constipation in cancer patients
true (e.g. senna and bisacodyl)
- osmotic agents (peg) may be used as well
