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*Pharmacotherapy 5270 > 25. Management of Chemotherapy Toxicities > Flashcards

25. Management of Chemotherapy Toxicities Flashcards

1
Q

this type of nausea/vomiting occurs despite prophylactic treatment and/or requires rescue

A

breakthrough nausea/vomiting

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2
Q

this type of nausea/vomiting occurs during subsequent cycles when antiemetic prophylaxis and/or rescue have failed in earlier cycles

A

refractory nausea/vomiting

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3
Q

explain the pathophysiology of acute CINV

A

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

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4
Q

explain the pathophysiology of delayed CINV

A

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

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5
Q

this type of CINV is very amendable to drug therapy. the primary mediator is serotonin and occurs within 24 hours of chemotherapy

A

acute

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6
Q

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

A

delayed

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7
Q

this type of CINV occurs before patients receive their chemotherapy, after a prior negative experience with chemotherapy (nausea > vomiting)

A

anticipatory

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8
Q

what are some treatment-specific risk factors for N/V

A
  • emetogenicity of chemo agent
  • tumor burden
  • combo of chemo agents
  • combined modality therapy
  • rapid infusion rate
  • repetitive daily doses
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9
Q

what are some patient-specific risk factors for N/V

A
  • children > adults
  • women > adults
  • alcohol history
  • hx of morning sickness
  • hx of motion sickness
  • prior CINV
  • depression and anxiety
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10
Q

what are some clinical consequences of CINV

A
  • metabolic derangements
  • nutritional depletion and anorexia
  • deterioration of patients physical and mental status
  • degeneration of self-care and functional ability
  • d/c therapy***
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11
Q

these agents can be given as a single dose prior to chemo.
- be careful with Qt prolongation

A

5HT3 antagonists (e.g. Ondansetron)

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12
Q

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

A

Palonosetron

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13
Q

what agent should always be given with a 5-HT3 antagonist before chemotherapy

A

dexamethasone

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14
Q

true or false: if a patient is getting Palonosetron instead of another 5HT3 antagonist, their dose of dexamethasone would need to be increased

A

false - Palonosetron is dexamethasone sparing therefore can cut back on doses of dexamethasone with this agent

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15
Q

list the NK1 receptor antagonsits

A
  • Aprepitant
  • Fosaprepitant
  • Netupitant
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16
Q

what CYP enzymes to Aprepitant/Fosaprepitant/Netupitant induce or inhibit

A
  • moderate inhibitor of CYP3A4 (therefore if administered with dexamethasone, decrease dex dose by 50%)
  • weak inducer of CYP2C9 (can affect warfarin)
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17
Q

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?)

A

olanzapine

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18
Q

if a patient is on an HEC chemo drug, what agents should be given pre-chemo for nausea?

A
  1. dexamethasone 8-12 mg PO
  2. NK1
  3. 5HT3 antagonist
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19
Q

if a patient is on a HEC chemo drug, what agents should be given post-chemo for nausea?

A
  1. dexamethasone 4 mg PO the evening of chemo then BID for 2-4 days
  2. +/- prochlorperazine or metoclopramide as needed
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20
Q

if a patient is on an MEC chemo drug, what agents should be given pre-chemo for nausea?

A
  1. dexamethasone 8-12 mg PO
  2. 5HT3 antagonist
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21
Q

if a patient is on an MEC chemo drug, what agents should be given post-chemo for nausea?

A
  1. dexamethasone 4 mg PO the evening of chemo then BID for 2-3 days
  2. +/- prochlorperazine or metoclopramide as needed
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22
Q

if a patient is on a low emetogenicity chemo drug, what agents should be given for nausea?

A

maybe something pre-chemo and maybe something post-chemo

23
Q

what are the 3 steps for managing a treatment failure

A
  1. rule out and treat other causes of n/v (e.g. medications, infection, gastritis, vestibular dysfunction)
  2. 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)
  3. 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?
24
Q

what side effects are expected of the following anti-emetic:
metoclopramide

A

EPS

25
Q

what side effects are expected of the following anti-emetic:
prochlorperazine

A

sedation and hypotension

26
Q

what side effects are expected of the following anti-emetic:
haloperidol

A

rarely EPS

27
Q

what side effects are expected of the following anti-emetic:
ondansetron

A

constipation and headache

28
Q

what side effects are expected of the following anti-emetic:
dimenhydrinate

A

sedation, dry mouth, blurred vision

29
Q

what side effects are expected of the following anti-emetic:
corticosteroids (dexamethasone)

A

insomnia, hyperglycaemia, heartburn, mood changes

30
Q

what side effects are expected of the following anti-emetic:
olanzapine

A

sedation

31
Q

what are some complications of diarrhea that we want to avoid through prevention and early/aggressive management

A

dehydration, electrolyte abnormalities and hypotension

32
Q

true or false: diarrhea often leads to dose reduction, delay in treatments or treatment discontinuation

A

true

33
Q

what are the 3 major mechanisms of chemo-related diarrhea

A
  1. increased secretion of electrolytes leading to secretory diarrhea
  2. increased intraluminal osmotic substances leading to osmotic diarrhea
  3. altered GI motility
34
Q

what are some therapy related risk factors for diarrhea

A
  • chemo
  • rads
  • multi-modailty tx
35
Q

what are some GI risk factors for diarrhea

A
  • previous GI surgery
  • IBD
  • lactose intolerance
  • nutritional supplements
  • dietary fibre
36
Q

what are some neurologic risk factors for diarrhea

A

anxiety

37
Q

what are some medications that may cause diarrhea

A
  • abx
  • laxatives and antacids
  • misoprostol
  • metoclopramide
38
Q

true or false: prophylactic anti-diarrheal treatment is a standard approach

A

false

39
Q

what is the initial management of uncomplicated diarrhea

A

give standard dose of loperamide
- inital dose of 4 mg then 2 mg q4h after each unformed BM

40
Q

what should be done if the patient still has persistant diarrhea after 12-24 hours of being on the standard dose of loperamide

A

increase loperamide to 2 mg q 2 hours (high dose loperamide)

41
Q

what should be done if the patient still has persistant diarrhea after 12-24 hours of being on high dose loperamide

A

add octreotide TID

42
Q

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

A

loperamide

43
Q

true or false: all doses of loperamide can can Qt prolongation

A

false - worry when get > 16 mg/day

44
Q

this anti-diarrheal agent contains a synthetic opioid chemically related to meperidine; it inhibits excessive GI motility

A

Lomotil (diphenoxylate)

45
Q

Lomotil contains a subtherapeutic amount of this medication to discourage abuse

A

atropine

46
Q

true or false: Lomotil is more effective than loperamide

A

false - loperamide is more effective, providing more rapid control of diarrhea and prolonging the time to first recurrence of diarrhea

47
Q

this anti-diarrheal agent is a somatostatin analog that decreases GI peptide secretion, splanchnic blood flow and GI motility and increases water absorption

A

Octreotide

48
Q

true or false: Octreotide is more effective than loperamide

A

true

49
Q

true or false: Octreotide is an oral agent

A

false - SC

50
Q

constipation in cancer patients is usually due to these TWO factors

A

poor oral intake and drugs (e.g. analgesics or antiemetics - ondansetron)

51
Q

what are some risk factors for constipation in cancer patients

A
  • 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
52
Q

true or false: enemas and suppositories are first line for constipation in cancer patients to reduce drug interactions

A

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

53
Q

true or false: a stimulant laxative is the first line for constipation in cancer patients

A

true (e.g. senna and bisacodyl)
- osmotic agents (peg) may be used as well

54
Q
A

*Pharmacotherapy 5270 (12 decks)

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