Cancer-induced N/V (CINV) EXAM 2

Question 1

What are the factors that determine the likelihood of N/V?

Answer 1

-specific drugs are more likely to cause emeses (Cisplatin)
-dose
-if you use multiple drugs
-IVP or CI

Question 2

Which moderate emetic risk drugs are known to have a high risk for Emesis when given together?

Answer 2

Anthracycline + Cyclophosphamide combination

not true for every combination

Question 3

What is the emetic risk for most monoclonal antibodies used in cancer treatment?

Answer 3

low or minimal emergetic

Question 4

What is the definition of acute emesis?

Answer 4

within 24h (peak = 4-6h)

Question 5

What is the definition of delayed emesis?

Answer 5

after 1-5 days (peaks 2-3d)

caused by
-Cisplatin
-Carboplatin
-Oxoplatin

-Cyclophosphamide
-Ifosfamide

-doxorubicin (also other anthracyclines, daunorubicin etc.)

Question 6

What is the best way to treat Anticipatory emesis?

Answer 6

anxiolytics (Benzos: Lorazepam, Diazepam)

-bc they had poor anti-emetic control at the first time, now the anxiety causes the nausea

Question 7

What is breakthrough emesis?

Answer 7

emesis despite optimal CINV prophylaxis
-> need to add more drugs

Question 8

Risk factors for CINV

Answer 8

-poor prior emetic control
-anxiety, depression
-women > men
-children> adults

-EtOH abuse can lead to reduced CINV

Question 9

What is the pathophysiology of vomiting induced by chemotherapy?

Answer 9

-peripheral release of 5-HT3 and NK-1

-stimulation of 5-HT3 and NK-1 receptors in the brain (CTZ and brain stem)

-autonomic response -> Vomiting

Question 10

Which cells in the GI release 5-HT3 during cancer treatment?

Answer 10

enterochromaffin cells in the GI tract

Question 11

What is the primary mediator (Neurotransmitter) in acute CINV?

Answer 11

-Serotonin !!!
-also NK-1

Blocking serotonin helps with acute N/V but not delayed vomiting

Question 12

Which mediator is associated with delayed vomiting in cancer therapy?

Answer 12

NK-1

(also involved in acute emesis)

Question 13

What are the common 5-HT3 and NK-1 antagonists used for CINV?

Answer 13

5-HT3 antagonist: Ondansetron

NK-1 antagonist: Aprepitant

Question 14

What are the main antiemetic drug classes?

Answer 14

-Corticosteroids
-5HT3 antagonists
-Dopamine antagonists
-Olanzapine (D2 antagonist and serotonin antagonist)
-NK-1 inhibitors

Question 15

What is a common side effect of 5-HT3 antagonists?

Answer 15

-headache

-ECG changes (QT prolongation) higher risk with > 4 mg given IVP
for 8 mg we give continuous infusion over 15 min

-no QTc prolongation with Palonosetron

Question 16

Where in the body do 5-HT3 antagonists work?

Answer 16

-Peripheral (GI): blocking 5-HT3 release from enterochromaffin cells

-central (brain): blocking 5-HT3 receptors in the medulla

Question 17

How is Ondansetron metabolized?

Answer 17

CYP 2D6
will not work well with ultra metabolizer -> change to Palonosetron (Aloxi)

Question 18

What is the brand name of Ondanstron?

Answer 18

Zofran

Question 19

What is the brand name of Palonosetron

Answer 19

Aloxi

Question 20

Which of the 5-HT3 has the longest half-life?

Answer 20

Palonosetron

works better for delayed N/V than Ondansetron

dexamethasone and prochlorperazine (dopamine antagonist) also work better for delayed N/V than Ondansetron

Question 21

Which drug has a synergistic effect when taken with other antiemetics?

Answer 21

corticosteroids (add to 5-HT3 antagonists like Zofran)

-BEST for delayed CINV
-synergistic with 5-HT3 -> helps with acute N/V as well

MOA unknown

Question 22

What are the side effects associated with corticosteroids?

Answer 22

-euphoria
-insomnia
-hyperglycemia
-immunosuppression (with long-term use)

Question 23

What is the brand name of dexamethasone?

Answer 23

Decadron

Question 24

What is the maximum dose of dexamethasone for antiemetic therapy?

Answer 24

20 mg

Question 25

Which Drug interactions are associated with NK-1 inhibitors?

Answer 25

-Fosaprepitant and aprepitant are CYP 3A4 inhibitors -Rolapitant is a CYP2D6 inhibitor

Question 26

Which drug combination includes an NK-1 inhibitor and can be used for delayed N/V?

Answer 26

-Neutpitant + palonosetron (5-HT3 with longer half-life) long halflife expensive -Rolapitant long halflife

Question 27

What is the brand name of Fosaprepitant and aprepitant?

Answer 27

Emend

Question 28

What is the MOA of Olanzapine?

Answer 28

-5-HT2A, 5-HT2C, 5-HT3 antagonist -Dopamine (1-4) antagonist -histamine (1) antagonist -antimuscarinic somnolence at days 2 to 3

Question 29

What is the brand name of Olanzapine?

Answer 29

Zyprexa

Question 30

What is the dose range of Olanzapine for CINV?

Answer 30

5-10 mg PO, Days 1-4 Day 1 for acute N/V Day 2-4 to prevent delayed N/V

Question 31

What is the drug of choice for anticipatory CINV?

Answer 31

Lorazepam (Ativan) others: Diazepam (Valium)

Question 32

What is the MOA of Prochlorperazine?

Answer 32

dopamine receptor antagonist works for breakthrough CINV

Question 33

What is the brand name of prochlorperazine?

Answer 33

Compazine

Question 34

What is the brand name of Promethazine?

Answer 34

Phenergan

Question 35

What are the side effects of prochlorperazine and promethazine?

Answer 35

-sedation -hypotension -anticholinergic -EPS -QTc prolongation !!!

Question 36

Name another Dopamine antagonist that is sometimes used for CINV.

Answer 36

-Haloperidol -Droperidol

Question 37

What is the role of Cannabinoids in cancer therapy?

Answer 37

chronic N/V from cancer and cachexia weight loss

Question 38

What are the options for acute, delayed and breakthrough N/V?

Answer 38

for acute: -5-HT3 -NK-1 -steroid in combi -Olanzapine for delayed N/V: -NK-1 -steroid with NK-1 -Olanzapine? for breakthrough N/V: -phenothiazine is BEST -Haloperidol (2nd line) -NK-1 -corticosteroid

Question 39

A woman receives Moderately Emetogenic Chemo (MEC). She has a history of anxiety and depression and had N/V during her last pregnancy. How many antiemetic drugs should she use? Design a CINV regimen.

Answer 39

for MEC we give 2-3 drugs + breakthrough meds PRN this patient has a higher risk for N/V so we give 3-4 drugs + PRN Acute: Ondansetron (5-HT-3) Delayed: Aprepitant (Emend, NK-1) Acute and delayed: Olanzapine Acute and Delayed: Dexamethasone PRN for home: Prochlorperazine (caution QTc)

Question 40

What is the dose of dexamethasone on day 1 when aprepitant, fosaprepitant or netupitant is part of the regimen for Cisplatin?

Answer 40

12 mg (instead of 20 mg) on day 1 we reduce the dose bc of CYP3A4 inhibition of aprepitant on day 2-4: 8 mg or 8 mg BID (depending on the NK-1, Fosaaprepitant CYP effect lasts until day 2, Rolapitant is a CYP2D6 inhibitor - no effect on dexamethasone)

Question 41

What is the dose of Aprepitant on day 1 and day 2 and 3?

Answer 41

day 1: 125 mg day 2 and 3: 80 mg

Question 42

What is the dose of Fosaprepitant for CINV?

Answer 42

150 mg IV only day 1 (the CYP 3A4 interaction lasts until day 2)

Question 43

What is the dose of Netupitant for CINV?

Answer 43

300 mg PO day 1

Question 44

What is the dose of Rolapitant for CINV?

Answer 44

180 mg PO day 1 (no CYP3A4 inhibition - no DDI with dexamethasone)

Question 45

Which drugs are known to cause delayed N/V? How should Dexamethasone be used for these drugs in a moderate-risk cocktail?

Answer 45

-doxorubicin -cyclophosphamide -oxaliplatin consider using dexamethasone 8 mg on days 1, 2, and 3 (usually dexamethasone is only given on day 1 for moderate risk cocktails)

Question 46

Which drugs counteract Parkinson's disease medication?

Answer 46

in Parkinson's we use dopamine agonists -dopamine antagonists can make Parkinson's worse Olanzapine Prochlorperazine Promethazine Haloperidol -consider THC, ginger, peppermint, acupuncture