Chemotherapeutic Flashcards
(60 cards)
1
Q
What are characteristics of cancer cells?
A
- Persistent proliferation
- unresponsive to feedback mechanisms that regulate cells
- Invasive growth/formation of mets
- malignant cells free of constraints that inhibit invasive growth–> cells of solid tumor can penetrate adjacent tissues and spread of cancer
- immortality
- cancer cells undergo endless division
- due to telomerase
2
Q
What are the 6 hallmarks of cancer cells?
A
- Sustaining proliferative signaling
- evading growth supressors
- activation invasion and metastasis
- enabling replicative immortality
- inducing angiogenesis
- resisting cell death
3
Q
How do cancers differ?
A
Based on phenotye, aggressiveness, responsiveness to drugs
4
Q
What 3 ways are cancers treated?
A
surgery
radiation
pharmacologic agents
5
Q
How does chemotherapy kill cancers (what order?)
A
1st order kinetic matter, generally kill 50% proportion
6
Q
What is palliative chemo curve representative of?
A
Treatment of a terminal Ca that does not have a cure.
More for symptom management
7
Q
WHat is adjuvant chemo?
A
Used after surgery to minimize tumor regrowth
8
Q
What needs to happen in order to reach a cure of cancer
A
Entirely free of disaes, and has same life expectancy as a cancer free individual
9
Q
What is a complete resposne from chemo?
A
Complete disappearance of all cancer without evidence of new disease for at least 1 month
10
Q
What is a partial response from chemo?
A
50% decrease in tumor size or other objective markers
11
Q
What is stable disease?
A
A patient whose tumor size neither grows nor shrinkgs by more than 25%
12
Q
What is tumor progression?
A
25% increase in tumor size or devleopment of new lesions while on tx
13
Q
Order of cell cycle events?
A
G0–> G1–> S–> G2–> Mitosis–> G0
14
Q
What is mitosis?
A
cell division
time span 1/2-1 hour (need high concentration of drugs)
15
Q
What is G0?
A
Resting
cells not committed to cell divison
(all neurons in resting)
16
Q
What is G1?
A
Postmitotic
enzymes necessary for DNA synthesis are made
17
Q
What is S phase?
A
Synthesis
10-20hours
cell doubles its DNA
18
Q
What is G2?
A
Premitotic phase
2-10 hours
Specialized proteins and RNA synthesis
19
Q
What are 7 calsses of chemotherapy/antineoplastic drugs?
A
- Alkylating agents
- antimetabolites
- antitumor antibiotics
- topoisomerase inhibitors
- tubulin binding drugs
- signal transduciton modifiers
- immunotherapy**< new approach
20
Q
Why are chemotherapy drugs combined?
A
Combination therapy preferred in order to:
- delay drug resistance
- decrease toxicity
- improve cancer cell death
21
Q
What is a broad summary of toxicity from chemo drugs?
A
-
Bone marrow suppressio (leukopenia, thrombocytopenia, anemia
- iatrogenic infection
- may need extra preop lab testing
- GI tract damage
-
N/V
- electolyte distubance, hypovolemia
- Aloplecia
-
mucosal ulceration
- avoid using oral airways, LMA, esophageal stethoscope
-
Reproductive
- infertility, teratogenic (1st semester, risk highest)
-
Urinary stones (uric acid crystals)
- Formed from breakdown DNA following cell death
- Extravasation: local injury
-
End organ damage and hepatic enzyme induction
- consider altered respones to anesthetics
- Promotion of secondary cancers
22
Q
What are the most common chemo drugs to cause extravasation?
A
- Anthracyclines
- Vinca alkaloids
- Taxanes
23
Q
Symptoms of extravasation?
A
- Pain
- burning
- swelling
- redness
- lack of blood return
- may require skin grafting/surgery
24
Q
What are some examples of aklylating agents?
A
- Nitrogen mustards
- Cyclophosphamide
- Nitrosureas
- Carmustine
- Platinum compounds
- Cisplatin
- Carboplatin
25
What is the MOA of akylating agents
* Reactive alkyl groups form covalent bonds with nucleotide bases in DNA/RNA
* Makes DNA be stuck in super coil
* if it cannot uncoil, can't replicate
* disrupts DNA synthesis and cell division--\> miscoding and strand breaks
26
Common toxicities in alkylating agents?
* **Bone marrow suppression- greatest concern**
* neutropenia, hemolytic anemia, thrombocytopenia
* mucositis
* skeletal muscle weakness
* sz
* **pneumonitis and pulm fibrosis**
* **carmustine pulm toxicity** similar to bleomycin 20-30% with **mortality 24-90%**
* Pericarditis and pericardial effusion
* inappropriate ADH secretion (Water toxicity)
* uric acid induced nephropathy
* **impaired pseudocholinesterase activity (2-3 weeks)**
* caution succ, mivacurium, esmolol, remi
27
What are the platinum compounds and toxicities?
Cisplatin, carboplatin
* **Nephrotoxicity**- cumulative and dose limiting; potassium and mag wasting and decreased GFR
* dose limiting toxicity for cisplatin
* hydration/supplemental electolytes
* may be on furosemide/mannitol to prevent
* hypomagnesium common
* *can also impact NM function*
* **Peripheral neuropathy**
* dose limited toxicity fo oxaliplatin
* presents as tingling around mouth, fingers, toes
* avoid cold contact
28
What are examples of antimetabolites?
* Folate analogues
* Methotrexate
* Pyrimidine analogues
* Fluorouracil (5FU)
* Purine analogues
* Mercaptopurine
29
What is MOA of antimetabolites?
* Strucutral analogues of natural metabolites (nucleic acid synthesis inhibitors)
* inhibit replication/repair of DNA by:
* Direct inhibition of enzymes needed for repair
* Incorporation of antimetabolite, directly into DNA
30
What is methotrexate's target of action?
* Folate must be taken up by cell and reduced to FH2--\> FH4 by dihydrofolate reductase in order to produce nucleosides
* **Methotrexate** has higher affinity for dihydrofolate reductase than does FH2, thereby preventing its reduciton to FH4
31
Toxicities of methotrexate?
* Pulmonary fibrosis (8%) and /or noncardiogenic pulmonary edema
* neutropenia and thrombocytopenia
* mucositis and GI ulceration
* GI perf possible
* Renal toxicity (10%)
* alkalinize urine and hydrate
* Hepatic toxicity
* often reversible
32
What is MOA of fluorouracil? Class of drug?
* Class= pyrimidine analog (antimetabolite)
* MOA- inhibits thymidylate synthetase--\> inhibits nucleotide production--\> inhibits DNA synthesis
33
Toxicity associated with fluorouracil?
* **Incrased risk of MI for 1 week after admin**
* Low threshold for EKG, echo, beta blocker, art line
* **Myelosuppression** (leukopenia, thrombocytopenia, and anemia)
* **alopecia**
* **neuro defects**
* ataxia (cerebellum)
* **GI toxicity** (d/c if stomatitis/mucositis/diarrhea)
* Pt at risk for GI ulceration and perf
* **Hand and foot syndrome**
* sx- tingling, redness, burning, flaking, swelling and blistering of palms/soles
34
What are examples of topoisomerase inhibitors?
* Anthracyclines (Doxorubucin, daunorubicin)
* Non-anthracyclines (Bleomycin)
35
What is MOA of topoisomerase inhibitors?
* Inhibition of topoisomerase I and II and intercalation of DNA--\> double strand DNA breaks and inhibition of DNA& RNA synthesis (replication)
* *topoisomerase II relaxes DNA supercoil and breaks strand for replication*
* *topoisomerase II also critical to the DAN strande being put back togheter*
* Generation of hydroxyl free radicals
* oxidative damage
36
What are some relatively minor s/e of anthracyclines?
* Bone marrow suppression (anemia, thrombocytopenia, low WBC 70% pt)
* Red/orange color of urine/swear
37
What is connection b/w cardiotoxicity and doxorubicin?
* May be sensitive to cardiac depressive s/e of anesthetics even in normal resting echo
* free radical produciton causes myocardial damage
* Acute (10%): tachycardia and arrhythmias
* transiet and rare
* ekg and acute EF reduciton
* usually lasts 1-2 mon
* Chornic (2% but with 60% fatality)**SEVERE** cmp/CHF
* related to cumulative dose
* protective therapies
38
What are some protective therapies for doxorubicin?
* Dexrazoxane
* prevents free radical formation
* ACE inhibitors
39
When would etomidate vs propofol be perferred in regards to cardiac dysfunction?
* If vasculature issue only, can still use propofol because myocardium hasn't been affected
* once myocardium affected, then etomidate is preferred
* can mix etomidate/propofol or give propofol very slowly and mitigate some effects
* If RSI and can't go slow, then etomidate preferred
40
What is MOA of bleomycin? Class?
Class= water soluble glycopeptides
* MOA- Topoisomerase inhibition and binds DNA and chelates iron leading to formation of free radicals that cause single and double strand DNA breaks
41
Main toxicity for bleomycin?
PUlmonary toxicity 4% (1% life threatening)
* Lungs take up high concentration of drug and lack hydrolase enzyme to inactivate bleomycin
* increased risk with:
* increased cumulative dosing
* age
* chest radiation
* pulmonary co morbidities
* oxygen exposure
* other chemo drugs
* genetics
* D/C agent at 1 st sign of dry cough, dyspnea, tachypnea and infiltrates on CXR
* may progress--\> pulm fibrosis--\> severe fibrosis--\> death
* decreased diffusion capacity
* **KEEP FIO2 CONCENTRAITON AT OR BELOW 30% DURING ANESTHESIA IF POSSIBLE**
42
What can bleomycin cause r/t hypersensitivity?
* Lymphoma pt; fever, chills, confusion, hypotension and wheezing
* test dose recommended for lymphoma pts before standard doses
43
Is myelosuppression seen with bleomycin?
No!
44
What are examples of vinca alkyloids?
* (vincristine, vinblastine, binorelbine)
45
What is MOA of vinca akyloids??
aka tubulin-binding drugs
* binds to tubulin (microtubule dimers) to block microtubules assembly (preventing polymerization (*aka forming)* of dimers)--\> cell division arrested during metaphase --\> apoptosis
46
Side effects of vincristine?
| (Class of vincristine?)
Vincristine= vinka alkaloid (tubulin binding drugs)
* Very little bone marrow suppression: good in combo therapy
* **hyponatremia** (inappropriate ADH secretion)
* **Peripheral neuropathy** via damage to neurotubules in almost 100% of aptients (reported to get wrose wiht sx/anesthesia)
47
What are some concerns with peripheral neuorpathy with vincristine?
* sensory loss,
* weakenss,
* autonomic dysfunction
* (constipation, ST, dry mouth, urinary retention, reflex lsos, cranial nerve-- laryngeala and extraocular dysfunction)
* usually resolves after treamtent
* uncertain w/ regional
* reduce local doses
* use US guidance
* no vasoconstrictors added
48
What is main side effect with vinblastine?
bone marrow suppression
49
What are examples of taxanes?
* Taxanes
* Paclitaxel
* Docetaxel
50
What is MOA of taxanes??
(Taxanes= tubulin-binding drugs)
* stabilizes microtubule bundles and prevents disassembly (prevents depolymerization)--\> inhibitng cell division and producing apoptosis
* (*kind of opposite from vincristine)*
51
What are some toxicities associated with taxanes?
* Peripheral neuropathy (esp hand and feet)
* muscle and joint pain
* hypersentiivity reactions 25-30% of pt
* Cardiaac
* bradycardia, heart block, MI
* Myelosuppression
* neutropenia develops in almost all pt
* 1% sepsis related deaths (11% if liver dx)
52
What are signal transduciton modulators?
Antiestrogens (tamoxifen)
antiandrogens (flutamide)
Monoclonal antibodies
aromatase inhibitors
53
MOA of antiestogens/antiandrogens?
* Disrupt aberrant growth factor: receptor interactions in cancerous cells preventing intracellular signaling that leads to cellular proliferation and survivial OR target mutated receptors that give a signal to proliferate even without any growth factors bound
54
How do anti-hormone drugs work?
* Work if the cancer cells expresses the particular receptor (and in proportion to the level of receptor expression)
* Tamoxifen- act as estrogen **antagonist** in certain cells (Breast and ovarian) and an estrogen **agonist** in other cells (uterus, liver, bone)
* s/e related to agonist activity : DVT, endometrial ca, menopausal symptoms, increased bone density (beneficial) and improves serum cholesterol panel (beneficial)
* **Antiadnrogens (prostate)**- gynecomastia, hot flasehs, muscle weakness and osteoporsis
* Flutamide- methemoglobinemia
55
What is hte MOA of monoclonal ab?
* Antibodies target specific proteins expresssed on immune cells, or that promote pro-survivial signaling in Ca cells
56
What is Gleevac?
Gleevac (Imantinib) is a tyrosine kinase inhibitor/antibody that can treat cancer when tyrosin kinase is mutated to be always on (BCR-Abl in chornic myelogenous leukemia)
- amazing drug that seems to cure problem
- can cause flu like symptoms
- used in autoimmune as well
57
What are aromatase inhibitors MOA?
* Aromatase is an enzyme complex that converts androgens to estrone peripherally
* Helpful to decrease estrone levels in some post-menopausal women with breast Ca
58
What is bevacizumab?
* Anti-angiogenic
* Trade name: avastin
* Monoclonal antibody that blocks angiogenesis
* Inhibits vascular endothelial growth factor-A
* without vascularization, tumors cannot survive
59
What is the basis for how immunotherapy works in cancer? Major s/e?
* Dendritic cells loaded with tumor lysate, the use of vaccines targeting tumor-sepcific epitopes, the generation of chimeric antigen receptor T cells and checkpoint inhibitors
* autoimmune reaction major concern with these approches
* flu like sympetomes
* **Biologically directed therapy**
* ****engineered viruses (oncolytic viral therapy)
60
General counseling guidliens for chemotherapy?
* These drugs are often mutagenic, carcinogenic and tertogenic: protect wourself if you are caring for someone still eliminating chemo!
* avoid contact with skin, eyes and mucous membrane
* follow hospital protocols
