Chemotherapy-Induced Nausea and Vomiting and Mucositis Flashcards
What percentage of oncology patients experience some type of nausea or vomiting
90%
What the three main areas of the body involved in CINV
Central nervous system, peripheral nervous system, and the GI tract
What are the two key reigons of the brainstem involved in CINV, what is the flow between the two
Chemoreceptor trigger zone and Vomitting center, CTZ stimulates the VC
What are the two pathways of the CTZ
Peripheral: chemotherapy directly irritating cells in the GI tract releasing serotonin stimulating the CTZ leading to stimulating VC (Acute CINV)
Central: Substance P binds to NK-1 receptors and dopamine is stimulated by CTZ (Delayed CINV)
Which patient risk factors increase the likelihood of CINV
Being female, age less than 50, history of motion sickness, previous CINV, N/V with past pregnancies, low alcohol use, Anxiety
T/F: Alcohol use makes it more likely a patient will have CINV
False: Alcohol use is actually PROTECTIVE against CINV
What are treatment related risk factors of CINV
Drug, dose, route, schedule, radiation, surgery
What are autonomic symptoms of nausea, what receptors are involved
Pallor, tachycardia, diaphoresis, salivation/ dopamine, serotonin, muscarinic, and histamine
T/F: Grade 1 and 2 in CINV can be resolved with outpatient care while Grade 3 and 4 may require hospitalization
True
What are the types of CINV
Acute. delayed, breakthrough, anticipatory, refractory
What causes acute CINV, when does it occur, peaks and resolves, mediated by
ANY CHEMOTHERAPY, within first 24 hours following chemotherapy, peaks after 5 hours to 6 hours and resolves in 24 hours, mediated by serotonin
What causes delayed CINV, when does it occur, peaks and resolves
Associated with platinum, anthracyclines, and nitrogen mustards/ 24 hours after chemotherapy, peaks at 48 hours to 72 hours and can last from 5 to 7 days, mediated by dopamine and NK-1 more than serotonin
What is breakthrough CINV, incidence, solution
Occurs despite prophylactic treatment and requires rescue with antiemetics, 10-40%, rescue antiemetics should utilize a different MOA
What is refractory CINV, solution
Occurs during subsequent cycles due to inadequate control in the previous cycles so patients have poor responses to multiple antiemetics
What is anticipatory CINV, triggers
Occurs before patient recieve their next chemotherapy cycle (mostly nausea)/ sight, smell, taste, sounds, thoughts, or anxiety associated with chemo
What is the corticosteroid used in CINV, what is it indicated in, MOA
Dexamethasone/ acute, delayed, breakthrough, refractory/ interaction with serotonin receptors, activation of glucocorticoid receptors, interaction with CTZ
T/F: Dexamtheasone has slow onset and low bioavailability
False: Dexamethasone has FAST onset and HIGH bioavailability
What are adverse effects of dexamethasone
Insomnia (take before 4 pm), GI upset (take with food), appetite stimulant (eat), anxiety, hypertension
What are the 1st generation 5HT-3 antagonists, which CINV is most affected
Ondansetron, Dolasetron, Granisetron/ prevention of acute and breakthrough
Which 1st generation 5HT-3 antagonist is most geared toward acute and delayed CINV
Granisetron
What are the 2nd generation 5HT-3 antagonist, which CINV is most effected, what makes it most different
Palonestron, acute and delayed, 100X higher affinity with a 40 hour half life
What are the adverse effects of 5-HT3 antagonists
Headache, constipation, fatigue, QTc prolongation (more common with IV)
When should 5-HT3 antagonist be given for chemotherapy
At least 30 mins to an hour
What are the three NK-1 inhibitors, what CINV do they block, which have IV formulations, which does not have drug interactions and why
Aprepitant, Fosaprepitant, Rolapitant/ Acute and Delayed/ Aprepitant and Fosaprepitant/ Rolapitant because it does not interact with CYP3A4 and CYP2C9
What are the adverse effects of NK-1 inhibitors
Fatigue, GI upset, headache, and HICCUPS
T/F: NK-1 inhibitors are NOT used in monotherapy and only used in HEC and MEC regimens
True
What are the two types of dopamine antagonists
Phenthiazines and substituted benzamine
What are the phenothiazines for dopamine antagonists, MOA, adverse effects
Prochloperazine and promethazine, antagonizes dopamine receptors in CTZ (can be used rectally)/ drowsines, EPS at high doses, CONSTIPATION, QT-c prolongation
What are the substituted benzamines for dopamine antagonists, MOA, adverse effects
Metoclperamide,Antagonizes dopamine receptors in CTZ and 5HT-3 receptors in the GI tract while also enhancing GI motility with more emptying/ DIARRHEA, EPS at high doses, QT-c prolongation
What antipsychotic can also be used for CINV, which CINV is it used for, receptors involved, Adverse events
Olanzapine/ Acute, Delayed, Breakthrough, Refractory/ Both serotonin, dopamine/ SEDATION, dry mouth, hyperglycemia and QT-c prolongation
What can used for anticipatory CINV, when should they take it
Lorazepam and Alprazolam, the night before or morning of chemotherapy
What are other antiemtics and what are they used for
Anticholinergics: Scopolamine, H1 blockers: meclizine or diphenhydramine, H2 blockers or PPIs: Ranitidine, famotidine, omeprazole or lasoprazole/ Refractory and Breakthrough CINV
What are synthetic THC products approved by the FDA
Dronabinol and Nabilone
What is the antiemetic backbone
Dexamethasone, 5-HT3 antagonist, NK-1 inhibitor
What are the HEC drugs
cisplatin, carboplatin (AUC greater than or equal to 4), doxorubicin greater than or equal to 60 mg/m2, epirubicin greater than 90 mg/m2, doxorubicin PLUS cyclophosamide, ifosamide greater than 2 grams/m2
What are the MEC drugs
Carboplatin (AUC greater than carboplatin), oxaplatin, doxorubicin less than 60 mg/m2, danorubicin, cyclophosamide, irinotecan and methotrexate at a high dose
T/F: HEC gets a 3-4 antiemetic regimen, MEC gets a 2-3 antiemetic regimen, Low gets one BUT if the patient has any type of Nausea/Vomitting regardless of regimen they get something
True
For HEC what drugs does the patient get on day 1, days 2-4 (take home meds)
5-HT3 therapy PLUS NK-1 inhibitor PLUS Dexamethasone 12 mg/ IF APREPITANT is used day 1 give 80 mg by mouth days 2-3 PLUS dexamethasone 8 mg daily days 2-4 regardless
For MEC what drugs does the patient get on day 1, days 2-3
take home meds
5HT3 (plonosetron or granisetron preferred) PLUS dexamethsone PLUS MAYBE an NK-1 inhibitor/ Aprepitant 80 mg by mouth days 2-3 if used PLUS dexamethasone 8 mg daily 2-4 regardless
What drug is used for a 4 drug regimen, what would it replace
Olanzapine, NK-1 antagonists
What drugs are given for low emetic risk
Dexamethasone 12 mg OR metoclopramide 10-40 mg OR Prochloperazine OR 5-HT3 antagonist (not long acting)
What is mucositis, pathophysiology, onset, resolution
Red ulcer and lesions that is present in the mucosa of the GI tract due to chemotherapy, initial tissue damage that cause reactive oxygen species that damages tissues causing inflammation and infection, 4-5 days post chemotherapy and 2 to 3 weeks after radiation, 2-4 weeks after chemotherapy
Grading for Mucositis
Grade 1: Minimal symptoms and normal diet
Grade 2: Symptomatic but can eat and swallow modified diet ( DOES NOT interfere with daily life)
Grade 3: Symptomatic and can take LIQUIDS ONLY
Grade 4: Sympotmatic and NEED TPN/ENTERAL FEEDING
What drugs are msot known to cause mucositis
Melphalan, Busulfan, high dose methotrexate, doxorubicin, epirubicin, sunitinib
What can be given for prevention of mucositis
Palifermin
