Therapeutics Exam 2 (Supportive Care) Flashcards
What is the most feared complication of chemotherapy?
Chemotherapy Induced Nausea and Vomiting (CNV)
What are the 5 types of Nausea/Vomiting?
Anticipatory
Acute
Delayed
Breakthrough
Refractory
What is anticipatory nausea/vomiting?
-A learned response conditioned by previous emetic reactions from prior cycles of chemotherapy
-Can be provoked by sight, sound, or smell
What is acute nausea/vomiting?
-Emetic response that correlates with the administration of chemotherapy
within 24 hours of receiving chemotherapy
What is delayed nausea/vomiting?
-Related to chemotherapy but occurs >24 hours after completion
What is breakthrough nausea/vomiting?
Occurs even though the patient is on scheduled anti-emetics prior to chemotherapy
What is refractory nausea/vomiting?
Persists despite appropriate anti-emetic therapy
-Patient has failed other therapies at this point
How does chemotherapy cause CINV?
It begins in the GI tract where cytotoxic chemotherapy induces damage to epithelial cells lining the GI tract
Enterochromaffin cells that line the GI tract contain large amounts of serotonin which is released in massive quantities
The chemoreceptor trigger zone (CTZ) stimulates the vomiting center (located in the medulla)
Input to the vomiting center from higher cortical centers such as the pharynx and GI tract induce emesis
Which cells are responsible for the massive release of serotonin in the GI tract after chemotherapy that leads to CINV?
Enterochromaffin cells
Which neurotransmitter can be targeted to treat breakthrough CINV?
Dopamine
What are the 2 most commonly targeted neurotransmitters for treatment of CINV?
Serotonin
Substance P
Which receptor mediates the action of substance P?
neurokinin-1 receptor
Which chemotherapy produces the most nausea?
Cisplatin
How does the combination of chemotherapies affect emetogenicity?
Level 1 and 2 agents do not contribute to the regimen’s emetogenicity
Level 3 and 4 agents increase the emetogenicity of the combination regimen by 1 level per agent
Who is at a higher risk for CINV: Men or Women?
Women
Who is at a higher risk for CINV: Younger Patients or Older Patients
Younger Patients
What are 4 risk factors of CINV?
Prior history of motion sickness
Prior history of morning sickness
Previous CINV
Anxiety/high pretreatment anticipation of nausea
What trait can be protective against CINV?
Chronic ethanol use
How do we decide what prophylaxis to use for acute nausea and vomiting?
It is based on the emetogenic potential of the chemotherapy
Which is more efficacious: Oral or IV CINV prophylaxis
NEITHER, their are equally effective
How many highly emetogenic regimens exist for acute N/V?
3
What are the 4 types of drugs included in the acute N/V highly emetogenic regimen A?
NK-1 Antagonist (“tant”)
(Aprepitant, Fosaprepitant, Rolapitant, Netupitant/palonosetron, Fosnetupitant/palonosetron)
Steroid
(Dexamethasone)
5-HT3 Antagonist (“setron”)
(Dolasetron, Granisetron, Ondansetron, Palonosetron)
Atypical Antipsychotic
(Olanzapine)
What are the 3 types of drugs included in the acute N/V highly emetogenic regimen B?
Atypical Antipsychotic
(Olanzapine)
Steroid
(Dexamethasone)
5-HT3 Antagonist
(Palonosetron)
What are the 3 types of drugs included in the acute N/V highly emetogenic regimen C?
NK-1 antagonist
(“tant”)
Steroid
(Dexamethasone)
5-HT3 Antagonist
(“setron”)
What three drugs can be added to any regimen at any emetogenicity if the patient is experiencing toxicities that might warrant a benzodiazepine or PPI?
Lorazepam
H2 Blocker (Pepcid/famotidine, calcium carbonate)
PPI (omeprazole, esomeprazole, pantoprazole)
For the moderately emetogenic regimen a, what are the 2 types of agents that should be used?
Steroid (dexamethasone)
5-HT3 Antagonist (dolasetron, granisetron, ondansetron, palonosetron)
For the low emetogenic regimen, what are the agents that you can pick from? (Pick 1)
Dexamethasone
Metoclopramide
Prochlorperazine
5-HT3 antagonists (Dolasetron, Granisetron, Ondansetron)
Treatment for delayed nausea/vomiting typically involves the use of one of which 3 agents?
Dexamethasone
NK-1 Antagonist
Olanzapine
Which drug can be used for treatment of anticipatory nausea and vomiting?
Lorazepam
When/how long should drugs be given for the highly/moderately emetogenic regimen?
Start before chemotherapy
Continue daily (5-HT3 antagonists)
When/how long should drugs be given for the highly/moderately emetogenic regimen?
Start before chemotherapy
May be given daily or prn
What is the treatment for radiation induced emesis?
Granisetron PO +/- dexamethasone
Ondansetron PO +/- dexamethasone
(5HT3 inhib + Steroid)
For which radiopharmaceutical is nausea associated with the amino acid infusion that accompanies treatment?
Lutetium Lu-177 dotatate
What are the common side effects associated with the 5HT3 Inhibitors? (trons)
Headache
Constipation
QTc prolongation
*note: if side effects occur you CAN switch to another agent in the same class, not a class effect
What are the common side effects associated with dexamethasone? (corticosteroid)
Hyperglycemia
Weight Gain (increased appetite)
What are the common side effects of Substance P Antagonists? (NK-1 antagonists) (tants)
Hiccups
What are the common side effects of the Dopamine Antagonists? (chlorpromazine, haloperidol, metoclopramide)
Extrapyramidal side effects
Diarrhea
What are the common side effects of olanzapine?
sedation
What are the common side effects of phenothiazines? (prochlorperazine, promethazine)
Sedation
What are the common side effects of the cannibanoids? (dronabinol)
Drowsiness
Weight Gain (increased appetite)
What are the side effects of lorazepam?
Sedation
What side effects are associated with the scopolamine patch?
Anticholinergic Side Effects
(can’t see, pee, shit, spit)
**Note: older people do not do well on this, primarily for use in young people
When are antiemetics most effective?
When given as prophylaxis
(5 to 30 mins before chemotherapy)
-Administer around-the-clock until chemotherapy is complete and provide prn agents for breakthrough
True or False: Mucositis is only in the mouth
False
-it can affect the entire GI tract all the way down to the colon
What is mucositis?
Ranges from mild inflammation to bleeding ulcers
-GI mucosa is comprised of epithelial cells and has a rapid turnover rate
What are the steps of progression for mucositis?
Parallels the neutrophil nadir
-Begins on day 5-7 after chemotherapy
-Improves as the neutrophil count increases
What are 2 chemotherapies to remember that cause mucositis?
5-FU
Anthrocycline
What are the 3 risk factors for mucositis?
Pre-existing oral lesions
Poor dental hygiene or poor fitting dentures
Combined chemo+radiation therapy
What are 3 dietary prevention methods to prevent mucositis development?
Avoid rough food, spices, salt, and acidic foods
Eat soft food or liquid food
Avoid smoking and alcohol
What are 3 mouthcare strategies for mucositis?
Baking soda rinses
Soft-bristled toothbrush
Saliva substitute (for radiation-induced xerostomia where the salivary glands are killed off)
What pain management strategies can be used for mucositis?
Topical anesthetics + Magic mouthwash (lidocaine, diphenhydramine, and antacid combos)
Oral cryotherapy
Sucralfate (swish and swallow, forms a protective barrier, can induce nausea)
Oral or IV opioids (for moderate to severe cases) PCA
How does oral cryotherapy reduce the risk for mucositis?
Causes vasoconstriction which may lower the amount of chemotherapy delivered to the oropharyngeal mucosa
What is the only way to get rid of mucositis?
Increase white blood cell counts
What white blood cell count is indicative of severe neutropenia?
<0.5 x 10^3/uL
What is the most common dose-limiting toxicity of chemotherapy?
Bone marrow suppression/ Neutropenia
What is the nadir?
The lowest value that the blood counts fall to during a cycle of chemotherapy
-Usually described by the absolute neutrophil count
-Generally occurs 10-14 days after chemo
-Counts normally recover by 3-4 weeks after chemo
How do we calculate Absolute Neutrophil Count (ANC)?
WBC x % Granulocytes
What are the typical guidelines used to assess if chemotherapy is safe to administer based on blood counts?
WBC > 3
ANC > 1.5
Platelet count > or = 100
True or False: Neutropenic patients are at an increased risk of developing infections
True
What values define febrile neutropenia?
ANC < 0.5
Single oral temperature >101F or >/= 100.4F for at least an hour
Get to hospital with this
Why is it so important for a patient to go to the hospital if they experience neutropenic fever?
The usual signs of infection (abscess, pus, and infiltrates on a chest x-ray) are not present because of the low levels of white blood cells
Fever is the only reliable indicator of infection
What can we use to increase WBC counts when they are low?
Colony Stimulating Factors (CSF’s)
What patients should receive primary prophylaxis for neutropenia?
-If they receive a chemo regimen expected to cause >/= 20% incidence of febrile neutropenia
-If they are high risk:
–Have preexisting neutropenia due to disease
–Extensive prior chemotherapy
–Previous irradiation to pelvis or other
areas with large amounts of bone marrow
What patients should receive secondary prophylaxis for neutropenia?
-Patient experienced a neutropenic complication from a previous cycle of chemo and now you want to prevent it from happening again
What 3 CSF’s can be used to treat neutropenia?
Filgrastim
Pegfilgrastim
Sargramostim
Which has the longer half-life: Filgrastim or Pegfilgrastim?
Pegfilgrastim
-more expensive
-1 time injection
Which medication used for treatment of neutropenia gets cleared more quickly as neutrophil counts increase?
Pegfilgrastim
Which form of filgrastim is not considered a biosimilar?
Tbo-Filgrastim (Granix)
Which form of filgrastim was the first approved biosimilar?
Filgrastim-sndz (Zarxio)
Which drug used for treatment of neutropenia is available as the Onpro kit?
(on-body self-injector kit that injects a dose of medication 24 hours after chemotherapy is received and prevents patient from coming having to come back to the hospital)
Pegfilgrastim
(note that this acts as a one-time injection)
When do we start filgrastim and how long is it continued?
Start 3-4 days after completion of chemo
Continue until post-nadir ANC recovers to normal or near normal
When do we start pegfilgrastim and how long is it continued?
Start at least 24 hours after chemo
Can be given up to 3-4 days after chemo
(at least 14 days should elapse between the dose and the next cycle of chemo)
OnPro body injector can be applied the same day as chemo
What are the common adverse effects of CSF’s?
Flu-like symptoms
*Bone + Joint Pain
DVT
What drug can be used to help with the side effects of CSF’s?
Loratadine
-because pain is thought to be due to histamine release
What is thrombocytopenia?
A platelet count < 100
At what platelet count should a transfusion be considered?
</=10
*may also be indicated at higher levels if the patient has active bleeding
What patients should undergo a work-up for anemia?
Hgb </= 11 g/dL OR >/= 2 g/dL drop from baseline
-want to determine cause
If a patient is experiencing symptomatic anemia, what are the 3 options for treatment?
Transfuse as indicated
Erythropoietic Stimulating Agents (ESA)
Perform Iron Study (need adequate iron for drugs to work)
What drug class has a black box warning for use in cancer patients and what is the warning?
Erythropoietin Stimulating Agents (ESA’s)
-cause shortened overall survival and/or increased risk of tumor progression
*note: use the lowest doses possible of these agents
*these are not used as commonly as they used to be
Who should ESA’s not be used in?
Patients receiving myelosuppressive chemotherapy with curative intent
Patients not receiving chemotherapy
Patients receiving non-myelosuppressive chemotherapy
Who should ESA’s be considered in?
Cancer and chronic kidney disease
Patients undergoing palliative chemo
Patients without other identifiable causes
What are the 2 commonly used ESA’s for chemotherapy-associated anemia?
Epoetin alfa (erythropoietin)
Darbapoetin (Aranesp)
When should we decrease the doses of epoetin alpha and darbepoetin during treatment of anemia?
If the Hgb increases > 1g/dL in a 2-week period
-Decrease epoetin dose by 25%
-Decrease darbepoetin dose by 40%
What patients should have baseline iron studies performed?
All patients prescribed ESA therapy
What are the 3 iron products that can be given to patients?
Low Molecular Weight Iron Dextran (Dexferrum)
Iron Sucrose (Venofer)
Ferric Gluconate (Ferrlecit)
Mesna should be used with doses of what chemotherapy?
Isofosfamide
Mesna is used to prevent what?
Hemorrhagic cystitis
How does cardiac toxicity occur?
Iron-dependent oxygen free radicals form
-Cause catalysis of electron transfer
-The myocardium is susceptible because it has lower levels of enzymes capable of detoxifying oxygen free radicals compared to other tissues
Which chemotherapy agents are most likely to cause Type 1 cardiac dysfunction?
Anthracyclines (doxorubicin)
Which chemotherapy agent is most likely to cause Type 2 cardiac dysfunction?
Trastuzumab
*not dose related
*not associated with cardiac damage (reversible)
-Involves the EGFR pathway (can restart therapy once EGFR goes back to normal)
Note: risk increases when used with anthracyclines, do not use these together
What are the assessment questions for pain?
OPQRSTU
-What is the onset?
-What provokes the pain?
-What is the quality of pain?
-Does the pain radiate?
-How severe is the pain?
-Time of pain?
-Understanding and Impact (what is the
patient’s understanding of their pain and
what is their goal)
What patient factors should we consider when determining appropriate analgesic therapy?
-Pain severity
-Medication access (price)
-Hepatic/renal function
-Previous analgesic therapy (did it work?)
What should Step 1 pain therapy consist of (mildest pain)(1-3 rating)?
Non-opioid
Adjuvant
What should Step 2 pain therapy consist of (moderate pain)(4-6 rating)?
Opioid for mild to moderate pain
Non-opioid
Adjuvant
What should Step 3 pain therapy consist of (most severe pain)(7-10 rating)?
Opioid for moderate to severe pain
Non-opioid
Adjuvant
When should morphine not be used?
Renal dysfunction!
-metabolites are excreted renally and will build up in renal failure
*use caution in liver dysfunction
Can hydromorphone be used in renal and hepatic dysfunction?
Yes but:
-Has renally excreted metabolites, lower dose or use longer dosing intervals in renal insufficiency
-Use caution in liver dysfunction
What is oxycodone metabolized by?
CYP2D6
Can oxycodone be used in renal and hepatic dysfunction?
Use caution in both
-Over sedation and CNS toxicity have been reported in renal failure patients
What formulation does oxycodone NOT come in?
No IV formulations
What opioid is the safest to use in renal dysfunction?
Fentanyl
metabolized in the liver but is safe in dysfunction
Besides renal dysfunction, Fentanyl also acts as a great alternative in which patients?
Refractory nausea/vomiting
Head/neck/esophageal cancer patients unable to maintain adequate PO intake
What is the REMS warning on fentanyl for?
Transmucosal and Nasal Preparations
-Risk of addiction, abuse, and misuse
-Respiratory depression
-Accidental exposure from improper disposal
-Avoid having the patch on a direct external heat source as this increases vasodilation, increases uptake, and can lead to overdose
Who should not receive fentanyl?
Opioid naive patients
Who should methadone be considered in?
Patients with:
-True morphine allergy
-Opioid-induced adverse drug reaction
-Refractory pain with other high dose opioids
-Neuropathic pain
-Who need long-acting po form at low cost
Who should not receive methadone?
Patients with:
-Numerous drug interactions
-Risks for syncope or arrythmia
-History of non-adherence
-Poor cognition
Can methadone be used in renal dysfunction?
Can be used in renal failure (no reported adverse effects)
BUT DO NOT USE IN SEVERE LIVER FAILURE
-QT prolongation
When switching between opioid agents, how much should we dose reduce by?
25% due to cross tolerance
What side effect in opioids do patients not develop tolerance to?
Constipation
Who can receive a Patient Controlled Analgesia (PCA) pump?
Only patients who are awake, oriented, and able to self-administer their doses
How do we calculate a patients total opioid usage with a PCA?
24-hour dose: Basal rate + Number of hits used daily
How do we decide what breakthrough (prn) dosing of opioids should be?
10-20% of patient’s total 24-hour oral dose
available every 4 hours prn (more often if IV)
What is the celiac plexus?
A group of nerves that supply organs in the abdomen
