Week 12 cancer - pharm Flashcards
What are the 6 barriers to chemo success?
- we don’t know when 100% of cells are killed
- drug resistance over time* most common cause*
- solid tumors don’t respond to chemo as well because of low growth fraction
- killing every malignant cell is almost impossible
- Kill both cancer and healthy cells
- Dosage is limited to the risk of toxicity to normal cells
What are 4 strategies for chemo success to optimize chemo results?
- Intermittent therapy
- Combination therapy
- Optimizing dose schedules
- regional drug delivery to the exact area and not systemic
What are the 6 major chemotherapy toxicities (consequences)?
- bone marrow suppression
- Digestive tract dysfunction
- alopecia
- reproductive toxcitiy
- local injury - Extravasation of Vesicants
- carcinogenisis
What type of cancer is surgery good for?
Solid and localized tumors
What is radiation good for?
Solid and localized tumors
What is chemo drug therapy good for?
Disseminated cancers
What does disseminated cancers mean?
They have spread throughout an organ or the entire body
What are the 3 examples of disseminated cancers?
- Lymphoma
- Leukemia
- Metastises cancers
What are the 4 major drug therapies for cancer ?
- Cytotoxic Agents (Chemotherapy)* most common*
- Hormones and Hormone Antagonists
- Biologic Response Modifiers
- Targeted Drugs
What is the main job of cytotoxic agents (chemotherapy)
Kill malignant cells
What is the main job of hormone and hormone antagonist drugs?
Stop cancer that uses hormones to grow
What is the main job of Biologic response modifiers (immunotherapy) ?
-Treat cancer by adding or changing body process already present (ie) enhance immunity
- Help with toxicities caused by some cancer drugs
What is growth fraction?
- explains why some tissues in the body are more prone to toxic chemo effects
- Cells in active proliferation phase and have high growth fraction will be killed more quickly
- cells in inactive G0 stage have a low growth fraction and are killed more slowly
Does cytotoxic chemo have a greater affect on high growth fraction cells or low growth fraction cells?
High growth fraction cells
What are examples of high growth fraction cells?
- bone marrow
- GI epithelium
- hair follicles
- sperm forming cells
What phase do cytotoxic drugs affect?
Active phase
disrupts DNA synthesis or Mitosis
Which cancers do not respond the best to chemotherapy (cytotoxic drugs) because they have a low growth fraction?
1.breast
2.colon
3.rectum
4.prostrate
5.lung
What cancers do respond better to chemo (cytotoxic) drugs because they have a high growth fraction?
leukemia
lymphoma
testicular cancer
What is the goal of chemotherapy?
Kill 100% of Neoplastic/malignant/cancer Cells while causing limited injury to normal tissues.
What is the most common cause of treatment failure in chemotherapy?
- drug resistance over time
What are the main treatments for solid tumors and why
- surgery - because they don’t respond well to chemo and you want to try to get it out
- chemo (adjunct) to kill any remaining cells left behind and prevent growth again
What is intermittent chemo therapy?
Think chemo rounds
- try to kill 100% and limit death of good cells
- give time for normal cells to repopulate but they have to do it faster than the malignant cells
- if the malignant cells grow just as fast as healthy ones then it will fail
What is combination chemo therapy and what are the 3 advantages?
Combine 2 or more chemo drugs
1. Reduce resistance and increase success
2. Increases overall cancer kill rate – MOA combo kills cells in more ways
3. Reduce toxicity to normal cells – especially if they don’t have overlapping toxicities
Why is optimizing dosing schedules important?
- to kill as many malignant cells as possible while maintaining healthy cells
What is regional drug therapy?
- Intra-artierial delivery - brain/liver artery
- intra-thecal delivery - bladder or peritoneal cavity
- Localizing it helps avoid systemic side effects
How do we know if someone is experiencing Anemia from a reduction in RBC from suppression of bone marrow (myelosuppression)
- SOB
- Fatigue
- Pallour
How do we know if someone is experiencing Neutropenia from a reduction in WBC from suppression of bone marrow (myelosuppression)
- Infection
How do we know if someone is experiencing thrombocytopenia from a reduction in platelets from suppression of bone marrow (myelosuppression)
- bleeding - low BP, high HR, weak
- bruising - petiche , ecchymosis
- GI bleeds - hemesis, occult/blood in stool
What is one of the most significant dangers of chemo drugs?
Infection due to suppression of WBC in bone marrow - can lead to sepsis
What measurement is Neutropenia?
<500mm3
How many days do we see a dip in Neutrophil levels?
2-3 days
When are patients most at risk of life threatening infection ?
Nadir
day 10-14
Why is Nadir so dangerous?
because the signs of infection are masked/not present
- > or = 38.0 (low grade fever) may be the only sign
What temp is considered low grade fever for chemo patients and signifies an emergency?
> or =38.0
What is the main sign of infection for someone with Nadir?
Fever
What are Hematopoietic Growth Factors also known as?
Colony Stimulating Factors
Biologic response modifiers
What are hematopoietic growth factor/colony stimulating factor/biologic response modifiers used for?
the effects of bone marrow suppression (myelosuppression)
1. neutropenia
2. thrombocytopenia
3. anemia
what makes stem cells turn into RBC, WBC or platelets from the bone marrow?
hematopoetic growth factor that tell the body which cell to make
What are the 3 categories of biologic response modifiers?
- Erythropoetin (RBC)
- Leukopoietic
- Thrombopoietic
Why can’t Epo be given to patients with myeloid malignancies and leukemias?
Because those are blood cancers and we could create more cancer growth of RBC
What drug can we never give PO?
Epo
What are the side effects of EPO? think thicker blood- clotting
- stroke
- heart failure
- MI
- blood clots
Who should EPO not be given to and why?
anyone who is not palliative because it can cause tumor growth and shorten life span
What is positive use of Epo?
to help increase quality of life for palliative patients experiencing the affects of anemia
what class is Filgrastim (Neupogen)?
Leukopoetic growth factor
What does Filgrastim (Neupogen) do?
increase neutrophil growth and help lower infection
Who should likely not receive Filgrastim (Neupogen)?
People who have bone marrow cancer because we don’t want to proliferate cancer cells
Does Filgrastim (Neupogen) have many side effects?
no
more commonly used
What drug class is Oprelvekin (Neumega)?
thrombocytopoetic growth factor
What does Oprelvekin (Neumega) do?
promotes platelet growth from stem cells in the bone marrow
What type of patients does Oprelvekin (Neumega) help?
those with thrombocytopenia and to help avoid needing a platelet blood transfusion
What cytokine does Oprelvekin (Neumega) look like in the bone marrow?
Nearly identical to Interleukin-11, a cytokine produced in the bone marrow
What is stomatitis?
inflammation of the oral cavity
how many days after starting chemo can stomatitis develop?
2-3 days (high proliferatin)
How long can stomatitis continue after treatment stops?
up to 2 weeks after
What can stomatitis cause in terms of symptoms?
- pain
- infection
- inflammation to ulceration
What are the 3 characteristics of bone marrow suppression in a chemo cancer patient?
- Neutropenia
- Thrombocytopenia
- Anemia
What are 3 characteristics of Digestive tract dysfunction in a chemo cancer patient?
- Stomatitis
- Diarrhea
- Nausea & vomitting
Why do people on chemo drugs experience diarrhea?
destruction of high proliferation epithelial cells in the GI tract
impacts absorption of nutrients and fluids
can lead to infection because skin is not great
What problem can excess diarrhea cause in people on chemo drugs?
- electrolyte imbalance
- dehydration
What problems do chemo patients with nausea and vomiting have?
- electrolyte imbalances
- dehydration
- esophageal tears (acid from emesis)
What aspect of digestive tract dysfunction is very common in chemo cancer patients?
Nausea & vomiting
Why does N & V occur in chemo cancer patients?
stimulation of the CTZ (chemical trigger zone)
how long does it take to develop N&V after beginning chemo treatment?
immediately - even after 1st dose
How long does N& V last?
hours or days
What are the 3 types of emesis in chemo cancer patients?
- Anticipatory emesis
- Acute emesis
- Delayed emesis
what three drugs are typically used for prevention of emesis in chemo cancer patients?
aprepitant + dexamethazone + ondansetron
When should antiemetic drugs be given before chemo dose to be most effective?
30 min before
Which one of the 6 major chemo toxicities happens with most cytotoxic medications?
Alopecia
How long after starting chemo does alopecia occur?
7-10 days
When does alopecia peak in chemo cancer patients?
1-2 months
How soon does hair grow back after stopping chemo treatment?
1-2 months
what are the 4 ways that chemo affects reproductive components?
- early embryo development interference
- fetal malformation & death (1st tri more so) >18 weeks = lower risk
- sterility in males - irreversible
- ovaries = amenorrhea & menopausal symptoms
What are vesicants?
highly chemically reactive drugs
cause severe injury if they directly contact tissue
How are vesicant drugs administered?
central line - highly diluted
What is extravasation?
the leakage of vesicant drug from the blood vessel into the surrounding tissues
What can extravasation cause?
pain,
infection
loss of mobility
in severe cases necrosis and sloughing
What are the clinical manifestations of extravasation and what should be done?
redness
swelling
blisters at the site
stop the infusion immediately
when can carcinogenesis occur?
years after treatment
what is carcinogenesis?
-cancer that occurs from cytotoxic drugs because of damaged DNA
- development of cancer (before treatment and after)
What drug class is Cyclophosphamide?
Alkylating agents
Which of the 4 types of cytotoxic anticancer drugs leads to carcinogenesis?
Alkylating agents
ie) Cyclophosphamide
What is the MOA of cyclophosphamide?
causes alkylation of DNA - destroys DNA in cancer cells
Is cyclophosphaide better for high growth fraction or low growth fraction and why?
High growth
because it affects WHOLE cell cycle so not G0 cells
What 3 of the 6 major cytotoxicities does cyclophosphamide affect? (think high fraction cells)
- bone marrow (myelosuppression)
- Digestive tract - GI epithelial cells, N&V
- Alopecia - hair loss
What is a unique side affect of cycloposphamide?
Bladder damage
1. acute bladder injury
-hemorrhagic cystitis
- hematuria
what do patients need to do when on cyclophosphamide to avoid bladder damage?
Drink lots of fluids/water!
Why should nurses use PPE with patients on cyclophosphamide?
to protect themselves from patient body fluids that could be toxic
What drug class is Methotrexate with cancer treatment?
Antimetabolites: Folic Acid Analogs
what phase does Methotrexate interrupt?
S- phase (synthesis)
(DNA replication)
What is the MOA of methotrexate?
-blocks folic acid from reaching its active form so no DNA synthesis
by blocking dihydrofolate reductase
What 2 of the 6 major toxicities does methotrexate cause?
1.bone marrow suppression (myelosuppression)
2. digestive tract dysfunction
- stomatosis oral
- GI ulceration
- N& V
What unique side effect does methotrexate cause?
Pulmonary fibrosis (scarring)
What is used to enhance the effects of methotrexate and reduce harm to normal cells?
Leucovorin (calcium Folinate) Rescue
What is Leucovorin (calcium folinate)
A reduced form of folic acid that lets some folic acid through to allow healthy cell DNA/RNA synthesis
When do you give Leucovorin?
24 hours AFTER methotrexate to rescue healthy cells
Does Leucovorin drug save malignant cells?
No it does not. only good cells can be saved
What is Leucovorin added to to enhance cytotoxic effects?
Fluorouracil (antimetabolite)
What drug is leucovorin added to and only then called a rescue drug?
methotrexate
What are the two types of antimetabolites and their drug exemplar?
- folic acid analog - methotrexate
- pyrimidine analog - fluorouracil
What phase does Fluorouracil affect?
S-phase (DNA & RNA synthesis)
What does Fluorouracil treat ?
Treat solid tumors
What is the MOA of Fluorouracil?
it inhibits thymidylate synthetase which is required by cells to make DNA
Does Fluorouracil cause pulmonary fibrosis?
No. that’s methotrexate
What drug type is Doxorubicin (Anthracycline Derivative) ?
Antitumor/antibiotic
What drug is Isolated from cultures of Streptomyces?
Doxorubicin
What is the MOA of doxorubicin?
gets into the DNA strands and binds to it
What type of cancer does doxorubicin treat?
- Solid (tumor)
- Disseminated
How is Doxorubicin always administered?
parenternally
Which of the 6 major chemo toxicities does it cause?
bone marrow suppression
What is a unique adverse affect of Doxorubicin?
cardiotoxic - can lead to fatal Heart failure
What are the 2 cardio reactions doxorubicin can cause?
- acute arrhythmia (lasts 2 weeks)
- delayed HF b/c of cardiomyophathy
What drug class is Bleomycin (Non-Anthracycline Derivative)?
Antitumor/antibiotic
What is the MOA of Bleomycin?
gets into DNA strands and binds to it
What cell cycle stage is bleomycin most effective?
G2 - growth and prepare for mitosis
What is a unique side affect of bleomycin?
Severe lung injury
Why is lung injury bad with bleomycin?
Lung injury manifests as pneumonitis which can progress to fibrosis and death
What 3 out of the major 6 major toxicities does Bleomycin cause?
- Digestive tract dysfunction
- stomatitis - Alopecia
- skin reactions
What drug class is Vincristine
?
Vinca alkaloid : Mitotic inhibitors
What stage does Vincristine affect most?
M - stage
prevent cell division
What is the MOA of vincristine?
Blocks mitosis during metaphase by disrupting the organization of microtubules (which normally move chromosomes during cell division)
Is Vincritine a vesicant?
Yes - must be administered IV
Which two cancer drugs minimally affect bone marrow?
- bleomyecin
- vincristine
Is vincristine toxic to peripheral nerves?
Yes
What unique side effects do patients on vincristine experience?
- sensory nerve injury
- paresthesia, weakness, sensory loss - motor nerve loss
- decreased reflexes
What drug class is Paclitaxel ?
Taxanes : Miotic inhibitors
What phase does Paclitaxel affect?
Acts during late G2 phase and M phase, inhibiting cell division
what is a unique side effects of Paclitaxel?
- severe hypersensitivity reaction
- hypotension
- dyspnea
- angioedema *
- urticaria
what are 2 of the 6 major cytotoxic affects of Paclitaxel?
- bone marrow suppression
- alopecia
What two drugs have cardiotoxic affects?
Paclitaxel
Doxorubicin
What happens in cardiotoxicity with Paclitaxel?
- bradycardia
- heart blocks
- MI
what are all chemo medications considered?
High alert - 2 nurse check
What are the 3 reasons nurses must be careful about chemo meds and bodily fluids from chemo patients?
- carcinogenic
- teratogenic
- mutagenic
What is the difference between Antiestrogens and aromatase inhibitors?
Antiestrogens - block receptors for estrogen
Aromatase inhibitors - block the synthesis of estrogen
What drug class is Tamoxifen?
Antiestrogen
Is breast cancer harder to treat in older or younger females when it is ER positive?
Younger
- because body hormones are feeding the tumor
What drug class is Anastrozole?
Aromatase inhibitor
What drug is Gold standard for hormonal treatment of breast cancer?
Tamoxifen
What drug can be used to prevent breast cancer in high risk populations?
Tamoxifen
What are the 3 potential adverse effects of Tamoxifen ?
1.Endometrial cancer
2. DVT
3. PE (pulmonary embolism)
What are the less serious reactions of Tamoxifen?
hot flashes, fluid retention, nausea, vomiting, and menstrual irregularities
Is Tamoxifen safe in pregnancy?
No it is not
What drug class is Anastrozole?
Aromatase Inhibitors
Which drug is Used more often in post-menopausal women (first line therapy) and why ?
aromatase inhibitor
-because they are not producing estrogen from the ovaries anymore.
They are getting estrogen from fat and skin to convert adrenal androgens into estrogen.
How does Anastrozole and Tamoxifen differ in adverse effects?
Anastrozole does not cause clotting issues or endometrial cancer
but it does cause
Increase in MI risk,
heart failure,
angina,
mood swings
depression
How long is treatment of Anastrozole?
2-5 years
What can anastrole do for cancer treatment?
Stop tumor growth
stop cancer cell growth
What are the symptoms of a PE ?
SOB
coughing up blood
Tachycardia
