Therapeutics V Exam 2- Supportive Care

Front 1

emesis is measured by...

Back 1

measured by the number of vomiting or retching episodes after treatment

Front 2

nausea definition

Back 2

patient’s perception that emesis may occur; feeling "queasy"

Front 3

what is the CTZ? (2)

Back 3

Central site located in medulla
Originally believed to serve as final common pathway for processing all afferent impulses that can initiate emesis

Front 4

what is the central pattern generator? (2)

Back 4

Loosely organized neuronal areas within medulla interact to coordinate emetic reflex
Involves variety of receptors


more accurate model- not just ONE SPOT (with the CTZ)

Front 5

is there a final common pathway for nausea/vomiting

implications for medicating

Back 5

No final common pathway, so no single agent can be expected to provide complete coverage

Front 6

how chemo induces nausea- via what transmitter (3)

Back 6

chemo sends message to brain

5HT3

then message back to stomach = puke

Front 7

sites of action slide

Back 7

---

Front 8

nausea/vomiting pathway- peripheral receptors located where (what are the cells called)?

what do they release?

Back 8

enterochromaffin cells in stomach-->releases serotonin-->message goes to brain-->vomit/nausea

Front 9

2 ways/pathways that chemo causes nausea

Back 9

Chemotherapy causes localized serotonin (5-HT) release from entero-chromaffin cells

5-HT interacts with 5-HT3 receptors on vagal afferent nerves, projecting to dorsal vagal complex on dorsal brain stem

Efferent fibers project from the dorsal vagal complex to central pattern generator

Antineoplastics may also induce emesis through direct interaction with the AP

Front 10

2 areas in brain where vagal afferent nerves carrying emesis signal project to

Back 10

nucleus tractus solitarius (NTS) & area postrema (AP)

Front 11

3 receptors present in CNS that are associated with nausea/vomit

Back 11

Neurokinin-1 (NK-1), 5-HT3, & dopamine-2 receptors are present here

Front 12

anti emetics most effect when given...when?

Back 12

Most effective when given prophylactically
PREVENT, PREVENT, PREVENT!!!

Front 13

general approach to administering anti-emesis for chemo (timing) (3)

Back 13

Begin therapy at least 30 minutes prior to chemo
Administer around‐the‐clock until chemo is complete, & provide PRN agents for breakthrough N/V
Provide patients with additional PRN anti‐emetics to take home after chemotherapy

Front 14

3 least sedating anti-emetics

Back 14

Butyrophenones (haloperidol) , corticosteroids, and serotonin antagonists

Front 15

EPS a risk from what 3 anti emetics

Back 15

with phenothiazines 9compazine, promethazine), butyrophenones, and metoclopramide

Front 16

Evaluate emetogenic potential & pattern of the chemo regimen: e.g. ...(2)

Back 16

Can be additive, i.e. combination regimens vs. single agents

May be different on different days of treatment (e.g., highly on day 1 and moderately on days 2 and 3); antiemetics should be tailored accordingly

Front 17

5 types of CIV (vomiting)

Back 17

acute- if multiple days of same drug- each day is considered acute
delayed
anticipatory
breakthrough
refractory

Front 18

acute vs. delayed CIV- timing

Back 18

acute- within first 24 hrs of receiving chemo

delayed- 24 hrs after & lasting up to 5 days

Front 19

breakthrough CIV- definition

Back 19

occurs despite preventatives

Front 20

4 drugs that commonly cause delayed CIV

Back 20

cisplatin, cyclophosphamide, carboplatin & anthracyclines

(basically alkylating agents...platins...anthracyclins)

Front 21

refractory CIV- definition

Back 21

occurs during subsequent cycles when antiemetic prophylaxis or rescue therapy has failed in earlier cycles (basically CIV that occurs no matter what you do)

Front 22

2 MAJOR risk factors for emesis

Back 22

EMETIC POTENTIAL OF DRUG (what drug are you giving)
DOSE OF MEDICATION

Front 23

6 (2 pt related, 4 hx related) risk factors for emesis

Back 23

Female
Age < 50
High pretreatment expectation of nausea or history of previous chemo-induced N/V (CINV)
History of low alcohol (high alcohol blunts your stomach rxn) consumption
History of motion sickness
History of morning sickness during pregnancy

Front 24

potential causes for nausea (8)

Back 24

Partial or complete bowel obstruction
Vestibular dysfunction
Brain metastases- red flag if they suddenly get nausea
Electrolyte imbalance: hypercalcemia, hyperglycemia, hyponatremia
Uremia
Other drugs (opiates)
Gastroparesis: disease (diabetes) or drug (vincristine and vinca alkaloids = constipation = backing up plumbing)
Psychophysiologic: anxiety or anticipatory

bottom line: many things that come into play and important to ID what is causing n/v

Front 25

emesis risk classifications (s anti emetic therapy) for chemo drugs (4)

Back 25

High: >90% of emesis*
Moderate: 30 – 90% of emesis*
Low: 10 – 30% of emesis*
Minimal: <10% of emesis*

Front 26

3 IV drugs that we have to know that cause emesis- and their risk classifications

Back 26

cisplatin- high emetic risk
etoposide- low risk
bleomycin- minimal risk

Front 27

place to look for emesis risk for oral drugs

Back 27

NCCN guidelines

Front 28

combination therapy that is really high risk for emesis

Back 28

AC combination (dox/cyclophosphamide)AC

Front 29

emend MoA (2)

what receptors and where

Back 29

substance P/NK1 antagonist

NK-1 receptors distributed throughout GI tract & CNS, but antiemetic activity believed to have central site of action

Front 30

High risk & AC treatment
(how many days...what to give on each day)

Back 30

Day 1: 5-HT3, dexamethasone (dex) & NK1 antagonist (NK1-ra: Neurokinen 1 receptor antagonist)
Day 2 & 3: dexamethasone & NK1-ra
Day 4: dexamethasone (optional) for delayed...

Front 31

moderate risk anti emetic regimen (how many days...what to give on each day)

Back 31

Day 1: Palonosetron (any 5HT3 will work) & dex, Day 2 & 3: dex

Front 32

low risk anti emetic regimen

Back 32

dexamethasone 8 mg Day 1 only

Front 33

minimal anti emetic regimen

Back 33

no routine prophylaxis

Front 34

when to try palonsetron (2)

Back 34

try palonosetron if ondansetron doesn't work

or multiple days of therapy- idk is palonsetron dosed shorter?

Front 35

what if you follow guidelines for ASCO and they still puke

Back 35

if you follow guidelines for anti emesis...and your pt still has it, bump them up a risk category and try that regimen next time

Front 36

if combo chemo, how to determine risk category

Back 36

administer anti-emetics appropriate for the agents of greatest emetic risk

Front 37

Multiple, consecutive day chemo- how to determine risk and regimen for anti emesis

Back 37

anti-emetics appropriate for the risk class of the regimen administered each day of treatment & for 2 days after

WHAT???

idk it sounded like you give the acute phase every day until it's done...then give dexa (delayed nausea ppx) after it's finished- ugh look this up

Front 38

radiation and n/v

what to give

Back 38

can cause n/v

give 5HT3 antagonists

Front 39

lower therapeutic index medications (6)

Back 39

Metoclopramide
Butyrophenones: (haloperidol, droperidol)
Phenothiazines (prochlorperazine)
Cannabinoids (dronabinol , nabilone)
Olanzapine
Scopolamine patch

Front 40

lower therapeutic index meds are used for...(2)

NOT used for?

Back 40

Not appropriate first-choice antiemetics
Reserve for patients who are intolerant of or refractory to 5-HT3ra, NK1-ra, & dex (as add-ons?)
Consider for rescue medication at home

Front 41

add on med of choice for anxiety induced


other med you can add as adjunctive therapy

Back 41

lorazepam


diphenhydramine

Front 42

Olanzapine pretty effective as

Back 42

an adjuctive for delayed N/V

Front 43

cannabinoids- 2

Back 43

nabilone, dronabinol

Front 44

dopamine antagonists- (3)

Back 44

antipsychotics (prochlorperazine/olanzapine), metoclopramide

Front 45

corticosteroid- 2

Back 45

methylpred, dexamethasone

Front 46

NK-1 blocker-

Back 46

aprepitant

Front 47

5HT3r antagonists- moa

Back 47

Selectively antagonizes 5-HT binding to 5-HT3 receptors on vagal afferents

Front 48

5HT3r properties (efficacy on acute vs dlayed)

Back 48

Most effective class for preventing acute; little effect on delayed

Front 49

AE of 5HT3a (4)

Back 49

usually no AE but...

headache, constipation, transient rise of hepatic aminotransferase levels; QTC elongation can occur from electrolyte imbalances

Front 50

5HT3ar properties (interchangeability, dosing intervals, PO vs. IV)

Back 50

Interchangeable at equivalent doses ***
Once-daily dose similar to multiple-daily dose ***
PO equivalent to IV***

Front 51

which 5HT3ar is CI for IV

Back 51

Dolasetron contraindicated IV adm

Front 52

Steroid of choice for n/v and why (2)

Back 52

dexamethasone

most literature, crosses BBB

Front 53

corticosteroids- efficacy for acute/delayed

Back 53

Effective for both acute & delayed- backbone for delayed emesis

Front 54

dexamethasones- interaction with what drug potentially?

dose adjustment if it's part of antineoplastic regimen too?

Back 54

Potential interaction with aprep; no dose adjustment when constitute part of the antineoplastic regimen- though if dose is high enough...you don't have to add on top of it for emesis

Front 55

oral vs IV name for NK1-antagonist

Back 55

Aprepitant--> Oral version- more expensive, part D??
Fosaprepitant--> IV version- medicare A

Front 56

dosing difference between apreiptant and fosaprepitant

Back 56

150 mg day 1 for IV (ONE DAY)

3 days for aprepitant (125 mg then 80 mg x 2)

Front 57

AE of aprepitant/fosaprepitant (6)

Back 57

hiccoughs, HA, constipation/diarrhea, fatigue or asthenia, hypotension, dyspepsia

Front 58

aprep/fosaprep- renal dosing adjustment?

Back 58

No dosage adjustments are recommend for either end‐stage renal disease requiring hemodialysis or severe renal insufficiency

Front 59

fosaprep/aprep- which phase will it treat of nausea/vomit?

Back 59

CNS activity- DELAYED- toxins are gone- out of stomach- 5HT3 is for acute...

if it's CNS then it can help delayed

Front 60

metabolism of fosaprep/aprep (3)

Back 60

Substrate of CYP3A4, but time of administration complications this

Administered for 3 days per cycle of chemotherapy, it is an inhibitor of the CYP3A4.
Administered > 14 days it’s a potent inducer of both CYP3A4 and 2C9

Front 61

any significant DDI with chemo drugs with aprep/fosaprep? (2) dose adjustments?

Back 61

No significant interactions with chemo have been identified but...

Study showed trend toward increased risk of ifosfamide neurotoxicity

No dose adjustments recommended

Front 62

regular drug DDIs with aprep/fosaprep (6)

Back 62

oral contraceptives
warfarin
dexamethasone
midazolam
CYP3A4 inhibitors
CYP3A4 inducers

Front 63

aprep/fosaprep DDI with oral conraceptives

Back 63

decreases efficacy; women of child‐bearing yrs should use alternative birth control

Front 64

a/f DDI with warfarin and what you need to do

Back 64

need INR checked 7‐10 days after aprepitant as there may be clinically significant decrease seen in INR

Front 65

a/f DDI with dexamethasone

most significant with what route

Back 65

increased dexamethasone AUCs were seen in clinical trials; most significant for PO administration

Front 66

a/f DDI with midazolam

Back 66

increased AUC ...of midazolam?

Front 67

3 CYP3A4 inhibitors

Back 67

erythromycin, itraconazole, ketoconazole

Front 68

3 CYP3A4 inducers

Back 68

carbamazepine, phenytoin, and rifampin

Front 69

3 meds you might see rx'ed for at home control of nausea (delayed)

indicate which is best/used most

Back 69

ondansetron- not that effectively used on a prn basis though...doesn't make sense to use in delayed nausea (which is what at home use is for)

metoclopramide in diabetic pt maybe or pancreatic cancer pt

but prochlorperazine used the most for home rescue use/control of N/V

Front 70

GI syndrome: consteallation of sx (4)

Back 70

Severe diarrhea, N/V, Anorexia, Abdominal cramping

Front 71

CID- thought to be caused by what?

results in what?

Back 71

Thought to be caused by direct toxicity to epithelial cell lining of the GI tract leading
Results in watery stool unaffected by fasting

Front 72

4 worst offenders for CID

Back 72

Fluorouracil (esp with high does leucovorin)
Methotrexate
Cytarabine
Stem cell transplant conditioning

Front 73

duration of therapy and effect on CID incidence

Back 73

Continuous infusions carry greater risk than short IV infusion

Front 74

chemo mechanism for CID- what type of diarrhea

Back 74

Stimulation of active secretion more than affecting the absorptive capacity of the intestinal epithelium

Front 75

sx of CID often associated with...(4)

Back 75

Symptoms were often associated with severe dehydration, neutropenia, fever, and electrolyte imbalances

Front 76

irinotecan CID- phasing

Back 76

has early (during infusion) & late onset phase (several days/weeks later)

Front 77

irinotecan Late onset (severe, potentially fatal) : type

how to treat

Back 77

secretory diarrhea
immediately treat with aggressive dosing of loperamide

Front 78

early onset component of irinotecan CID- mechanism

treat with what

Back 78

Cholinergic process: facial flushing, diaphoresis, “hypersecretion”, and abdominal cramping
Treat with atropine (scopolamine prophylaxis?)

Front 79

Management of uncomplicated mild to moderate diarrhea (non pharm) (3)

and pharm

Back 79

Stop all lactose-containing products and alcohol
Frequent small meals & push oral hydration (e.g., 8‐10 glasses of clear fluids)
Instruct pts to record # of stools & any symptoms

Loperamide- 2 tabs...then 1 tab after every loose stool. if exceed 4 tabs call dr

Front 80

if diarrhea resolves- what should pt do? when can they d/c loperamide?

Back 80

Continue dietary modifications & gradually add solid foods
Patients can discontinue loperamide when diarrhea-free for at least 12 hours

Front 81

if CID persists for more than 24 hrs on loperamide...

Back 81

increase loperamide to 2 mg Q 2 hrs & consider starting oral antibiotics for infection prophylaxis (increase dose)

Front 82

if CID persists for more than 48 hrs on loperamide (24 hrs after starting high‐dose loperamide) (3)

Back 82

Stop loperamide and start 2nd‐line antidiarrheal

Complete stool & blood work‐up (cdiff, toxins)

replace fluids & electrolytes as needed

Front 83

4 2nd line anti diarrheals

Back 83

octreotide 100 to 150 mcg SQ
tincture of opium 10 to 15 drops in water Q3‐4 hr
paregoric 5 mL in water Q3‐4 hr
budesonide

Front 84

what to do for pt with complicated diarrhea (5)

Back 84

Admit to hospital for IV hydration and electrolyte replacement

give SC octreotide if severe dehydration and escalate dose until diarrhea controlled (up to 500 mg q8h)

IV antibiotics as needed, e.g., fluoroquinolone, metronidazole

Complete stool and blood work‐up

d/c chemo til sx resolve-->consider reducing dose for next cycle

Front 85

complicated diarrhea definition

Back 85

5 bowel mvmts in a 12 hr period