NURS-304 Exam 2: Podcast 10 (Drugs for Neoplasia)

Miscellaneous Antineoplastics

1.) *Asparaginase* deprives cancer cells of essential amino acids and won't allow cancer cells to replicate 2.) *Mitotane (Lysodren)* is similar to insecticide DDT → DDT is an insecticide we encourage hikers and those looking to avoid mosquito bites to use more liberally, but it can also kill cancer cells! 3.) Two new antineoplastics inhibit the enzyme tyrosine kinase in tumor cells → *imatinib (Gleevec)* and *sorafenib*

Antitumor Antibiotics

1.) Act by inhibiting cell growth through cytotoxicity (cell death) → Actions similar to alkylating agents 2.) Narrow spectrum of clinical activity 3.) Cardiotoxicity is a major limiting factor → May occur within *minutes* or *years* later

Hormones/Hormone Antagonists

1.) Antineoplastic (neoplastic) agents slow the growth of reproductive related tumors → Breast, prostate, uterine 2.) Less cytotoxic than other antineoplastics 3.) There are many hormones/hormone antagonists such as: → *Glucocorticoids* → *Progestins* → *Estrogens* → *Androgens* *The mechanisms of action for these are largely unknown, but we know they block substances that are needed for cellular growth*

Alkylating Agents

1.) Broad spectrum of activity 2.) Act by changing the structure of the DNA in cancer cells (limits the ability of cells to replicate) 3.) Use is limited - it can cause significant bone marrow suppression → We want to alert patients that they are at risk for infection (family members too!) ↪ Strict hand washing guidelines and avoiding bringing small children (as they touch all surfaces) into the hospital during the patients vulnerable time (where infection *must not* be spread) ↪ Should family members, or any members of the health care staff, feel or be ill (even if it just a runny nose) they should not be coming into the hospital or having any contact with our patients. We can especially give them bacteria and viruses (especially those patients using chemotherapy) ↪ *This can be life threatening* (so if you are sick you *have* to go home!)

Radiation

1.) Can destroy tumor cells 2.) Ionizing radiation is aimed directly at the tumor (which means it is attempting to only affect the tumor itself) 3.) May follow surgery 4.) Used as *palliation* (to relieve or lessen without curing) for inoperable cancers in order to: → Shrinks the size of a tumor → Relieves pain, difficulty breathing or swallowing (alleviate pain or symptoms brought on by the tumor itself) *It is important to remember that some radiation, a little bit of radiation, any kind of radiation, can always trigger cancer!*

Some Major Points

1.) For a cure for cancer, every cancer cell *must* be killed 2.) We try to target cancer cells at their highest growth fraction 3.) Typically, multiple drugs are used, and a combination of surgery, radiation, and chemotherapy are used. 4.) The major toxicities that we saw were bone marrow suppression and we know that when patients are at their nadir, they are at their lowest blood level counts 5.) We are concerned with severe diarrhea, nausea, and vomiting, infertility, and possibly the formation of other cancers

Achieving Total Cure

1.) In order to get a total cure, every malignant cell must be removed or killed from the body and: → Even one cell could reproduce → Immune system eliminates a very small number of cancer cells ↪ *Tumor necrosis factor*: something within our bodies that helps us rid mutated cells everyday 2.) It is important to diagnose cancer early in order to have the options for cure (we do not want it to grow and metastasize) → Treat with surgery, radiation, or chemotherapy

Natural Products

1.) Plant extracts → Strictly very different → Kill cancer cells by preventing cell division → Called mitotic inhibitors 2.) Patients taking these are at risk for *bone marrow suppression*

Alkylating Agents (prototype drug)

1.) Prototype drug: *cyclophosphamide (Cytoxan)* 2.) Mechanism of action: Attaches to DNA and disrupts cellular replication → Alkalization changes the shape of cellular DNA (the alpha helix) and deters normal cell division from occurring 3.) Primary use: To treat a wide variety of cancers, including Hodgkin's disease, lymphoma, multiple myeloma, great cancer, and ovarian cancer → Blood cells are very sensitive to alkylating agents 4.) Adverse effects: We will see bone marrow suppression as an adverse effect (which places the patient at risk for infection), immunosuppressant effects (from bone marrow suppression), thrombocytopenia (the risk for bleeding is high) → Nausea, vomiting, anorexia, diarrhea → Alopecia (loss of hair), hemorrhagic cystitis (you can see sudden blood in the urine due to irritation of the Genitourinary tract) *The first alkylating agent was called nitrogen mustard, and allay*

Antitumor Antibodies (prototype)

1.) Prototype drug: *doxorubicin (Adriamycin)* 2.) Mechanism of action: Works by attaching to the cells DNA → Distorts double helical structure of the DNA and prevents normal DNA and RNA synthesis 3.) Primary use: Solid tumors of the lung, breast, ovary and bladder, and for various leukemias and lymphomas 4.) Antitumor Antibiotics are obtained from bacteria to have the ability to kill the cancer cells! 5.) Administration: Giving the line through an IV that the doctor placed in one of the larger veins (*central line*) → Doxorubicin is a vesicant and extravasation can cause severe pain to the patient → If the IV slips out and the medication leaks into the surrounding tissues (peripherally or in a central line) we need to put some ice on it and alert the doctor immediately 6.) Adverse Effects: Cardiotoxicity and dysrhythmia (which are both dose dependent), irreversible heart failure, lower blood cell counts (low WBC count, low RBC count, or low platelet count)

Antimetabolites (prototype drug)

1.) Prototype drug: *methotrexate (Folex, Mexate, Rheumatrex, others)* 2.) Mechanism of action: Blocks synthesis of folic acid (vitamin B9) to inhibit replication of cancer cells → Folic acid analog 3.) Primary use: To treat choriocarcinoma, osteogenic sarcoma, leukemias, head and neck cancers, breast carcinoma, lung carcinoma 4.) Adverse effects: Bone marrow toxicity 5.) Administration: We want to avoid skin exposure to the drug (for you and the patient; we wear protective gloves) → Many of the chemotherapeutic drugs are *vesicants* and they cause skin necrosis, which could lead to an amputation. So, you want to be very careful that these medications do not extravasate, go into local tissues, or get on your (or your patients) skin, or splash into your eyes → Many times the pharmacist will dilute this product before administration because it can be caustic to the veins 6.) Pregnancy Category: X (will not give this to anyone pregnant) 7.) Overdose: If there is an overdose, we can give a drug called *leucovorin*. Leucovorin is folinic acid, which can help reverse the damage done by methotrexate → Leucovorin can rescue the normal cells

Hormones/Hormone Antagonists (prototype)

1.) Prototype drug: *tamoxifen (Nolvadex)* 2.) Mechanism of action: blocks estrogen receptors on breast cancer cells 3.) Primary use: Clients with breast cancer (treats metastatic breast cancer!) → Also given to high risk clients to prevent disease ↪ Many women are being tested for the oncogene, and if they have the positive cancer gene, oncologists may choose to offer tamoxifen to delay the epigenetic trigger and delay the oncogene from promoting breast cancer (*prophylactic use*) 4.) Interactions: We like to give this drug with food or with oral fluids, but never crush it orally. Also, never give it with an antacid because it can lower the absorption rate 5.) Adverse effects: Nausea and vomiting (cancer induced side effects are very severe and it is best to tell the patient to be proactive with their approach and management for nausea and vomiting) → Association with increased risk of *endometrial cancer* and *thromboembolic disease* ↪ Meaning, when you take this drug, you can get a deep vein thrombosis (DVT) formation or you are also at high risk for a pulmonary embolus → Hot flashes, fluid retention, vaginal discharges common

Natural Products (prototype)

1.) Prototype drug: *vincristine (Oncovin)* 2.) Mechanism of action: Cell-cycle specific (*M-phase*) age that kills cancer cells by preventing their ability to complete mitosis (interrupts cell division/mitosis) 3.) Primary use: Treatment of Hodgkin's and non-Hodgkin's Lymphomas → Leukemias, Kaposi's sarcoma, Wilms' tumor → Bladder carcinoma, breast carcinoma 4.) Adverse effects: Has been associated with nervous system toxicity, numbness and tingling in limbs → Muscular weakness, loss of neural reflexes, pain → Paralytic ileus, constipation, alopecia 5.) Since it is a natural product it is derived from many plants, but mostly, the *periwinkle* 6.) Administration: If extravasation occurs you will see very bad tissue damage. In the event that this is suspected, stop the injection, call the doctor, and apply a warm compress. → We will continue to watch for sloughing of the skin!

Biologic Response Modifiers

1.) Stimulate or assist client's immune system to rid itself of cancer cells → Less toxic than other classes of antineoplastics → Includes interferons, interleukins, and monoclonal antibodies → Given concurrently with other neoplastic (chemotherapeutic agents) to limit immunosuppressive effects

Chemotherapy

1.) When it comes to drugs that can kill cancer, they are transported through blood so that they: → have the potential to reach each cancer cell 2.) Some drugs/chemotherapy can cross the blood-brain barrier 3.) Some drugs are distilled directly into body cavities (ex: bladder [for bladder cancer]) 4.) Often combined with or done after surgery and radiation to increase the chance of a cure → Called *adjuvant* therapy ↪ This means that this combination approach will remove the cancer that the surgery didn't → In advance stages, cure or control may not be obtainable → *Palliative treatment* (which means symptom control) can help patients be more comfortable, despite our inability to stop the cancer from advancing

Antimetabolites

Antimetabolites interfere with the nutrients needed for cellular proteins. 1.) They act by directing critical pathways in cancer cells (ex. folate metabolism or DNA synthesis) 2.) There are three types of antimetabolites: → *Folate analogs* ↪ Block cellular metabolism → *Purine analogs* ↪ Interfere with DNA production ↪ Masquerade as purine/pyrimidine which become the building blocks of DNA ↪ Purine analogs prevents pyrimidines from being incorporated into DNA, which stops cellular division → *Pyrimidine analogs* ↪ Directly block DNA synthesis

The Side Effects of Chemotherapy

Antineoplastic agents are associated with adverse effects such as: 1.) *Anemias*: Low red blood cell counts 2.) *Leukopenia/Neutropenia*: Low white blood cell count 3.) *Thrombocytopenia*: Low platelet count 4.) *Anorexia*: A loss of appetite 5.) Bleeding of the gastrointestinal tract 6.) Nausea, vomiting, and diarrhea 7.) Loss of hair, fatigue, and fetal defects/fetal death (if someone conceives during the time period of drug therapy) can occur

Growth fraction

Antineoplastics target cells undergoing mitosis division. The *higher the growth fraction, the better the drug will work!* 1.) The growth fraction is a measure of how many cells are undergoing mitosis (or cell division) → Ratio of replicating cells to resting cells 2.) Major factor in determining success of chemotherapy 3.) Chemotherapy is the most effective against *rapidly dividing cells*! So, we want to target cells during their highest growth fraction (high growth fraction for many replicating cells)! 4.) Solid tumors have *low growth fraction*; thus, they are *less sensitive to chemotherapy* (they do better with surgery) 5.) Leukemias and lymphomas have high growth fraction (rapidly divide); thus, chemotherapy is more effective 6.) Hair follicles, bone marrow, and gastrointestinal tissue all have high growth factor. This explains many of chemotherapies adverse effects: → *Alopecia* (loss of hair) → Bone marrow suppression → GI upset *This is because the chemotherapy targets all cells, even the healthy ones!*

Cancer (carcinoma)

Cancer is uncontrolled cell division and the only way to diagnosis cancer is to biopsy it. When we biopsy it, and it is cancerous, we will see anaplasia. 1.) Characterized by rapid and uncontrolled growth of cells 2.) Cells lose normal functions and invade normal tissues 3.) *Metastasize*: the ability for a cancer cell to travel to another location

What type of chemotherapy is there?

For antineoplastic drugs we have: 1.) *Alkylating agents* 2.) *Antimetabolites* 3.) *Anti-tumor antibodies* 4.) *Hormones* 5.) *Natural products* 6.) *Biologic modifiers* 7.) *Some Miscellaneous agents*

Nadir

It is very important that the nurse understand what nadir is. *Nadir* is the lowest point to which blood cells are reduced. 1.) Each antineoplastic as their own nadir 2.) So when cells are at their nadir everything is at their lowest! 3.) This is when patients are most seceptible to: → Bleeding → Infection → Fatigue → Anemia *In the bone marrow, the spongy inner core of the larger bones in the body is where blood cells are made. There are very immature cells called stem cells, from which the various types of blood cells develop. These stem cells do not reproduce quickly and are less likely to be affected by chemotherapy. As cells are maturing there are certain phases in which they divide faster. It is during these times that the cells are most sensitive to chemotherapy. The more mature cells can continue to become fully mature cells for several days after chemotherapy is given. When these cells live out their life span, the circulating supply is depleted and the blood counts fall to a low point, the nadir.*

Tissue of Origin

Neoplasms will be classified or named according to the tissue from which they grow along with the suffix, *"oma,"* for tumor. 1.) A benign tumor will have the suffix "oma" added after the name of the tissue → Ex. Lipoma (a benign tumor of fatty tissue) 2.) A malignant tumor will have the term *"carcinoma"* or *"sarcoma"* added to the name of its tissue

Surgery

Surgery can be done at the discretion of the surgeon, or when it is an impinging a nerve or any other vital areas. 1.) Performed to remove a tumor → When localized → When pressing on nerves, airways, or other vital tissues 2.) Radiation and drug therapy are more successful than just surgery alone 3.) Surgery sometimes is not an option (not an option for every patient) → If tumors affects blood cells → If surgery would not extend the lifespan or improve quality of life

Patients Receiving Antineoplastic Therapy

There are some major points to remember about chemotherapeutic agents. 1.) Implementation: → We must monitor labs and see if the patient has reached their nadir → We want to trend their WBCs, RBCs, and platelets → Check if they are at risk for infection or bleeding → Monitor CBC and temperature → Collect stool samples for guaiac testing of occult blood (testing for gastrointestinal bleeding; if not seen you need to ask the physician for a guaiac test for hidden or occult blood) → We monitor vital signs and use vital signs to interpret what they mean to their cardiorespiratory and respiratory status (also need to do a full physical assessment) → Monitor renal status, urine (observe, color, consistency, and amount), intake and output, and *daily weight (best measure of overall fluid status)* → Monitor GI status and nutrition (make sure they are eating and are addressing their chemo induced nausea) → Administer antiemetics 30-45 minutes prior to antineoplastic administration to cut down on the chemo induced nausea and vomiting → Monitor for constipation (keep track of their bowel movements; we also offer oral fluids), presence of pain → And if the doctor permits, we asses and monitor neurological (by looking at their LOC)/sensory status, level of consciousness → Monitor genitourinary, hepatic status (by checking their BUN, creatine, GFR [Glomerular filtration rate; serum blood test], and serum liver function tests) → Monitor for hypersensitivity (breathing, itchiness, or pain) or other adverse reactions (ototoxicity) ↪ Ask about their hearing. Ask if they are turning up the volume on the TV more than usual, or are you asking you family members to repeat themselves more often → Protect the patient from infection ↪ We want them to wear a mask when they go out in public when they are taking chemotherapy ↪ We also want to keep them away from public places. Limiting visitors is a good idea and encourage anyone feeling in the least bit sick to not visit → Monitor hair (alopecia) and skin status → Monitor their eyes for excavate or *conjunctivitis* → Check the oral cavity for dryness; looking for irritation known as *mucositis* → We want to monitor patients liver and kidneys by looking at serum blood tests and trending their BUN, creatine, GFR (Glomerular filtration rate; serum blood test), and serum liver function tests (LFTs) ↪ Monitor liver function tests! → Administer with caution to clients with diabetes mellitus because chemo agents can elevate blood glucose levels. So, we monitor finger sticks even more frequently on our diabetic patients → Provide for adequate pain (administer analgesics) medication and encourage rest periods throughout the day (encourage family members to do the same; ask them about their rest plan for the day so we can all agree on devoted time for each person to have their down time and sleep periods; naps are essential for patients to get better in the hospital) → Provide emotional support for patients and family (often it is just us listening and waiting when we ask "How is your day going"; To encourage them to talk about can ask "Can you tell me more about that") ↪ Support groups, when someone has cancer, are very important so use your units resources and refer your patents and families

Carcinogens Around Us

Things that cause cancer are known as *carcinogens*. 1.) Home and environment → Pesticide, aerosols, UV rays, radon, vehicular emission 2.) Foods → Preservatives, sweetened juice, dietary fat, highly spicy food, fermented food 3.) Lifestyle → Tobacco chewing, body piercing, tar from smoking 4.) Industry → Vinyl on paint, gamma radiation, asbestos, sand dust, raw dust, wood dust 5.) Viruses → Herpes virus, hepatitis B & C, HPV, H. Pylori

Treatment of Cancer

When it comes to cancer sometimes we can do surgery, radiation therapy, and drug therapy. These treatments are often used alone, as well as, physicians use combinations of therapy. SO: 1.) Surgery, radiation therapy, drug therapy (chemotherapy) 2.) There are three goals when using pharmacotherapy in treating cancer patients: → To cure the patient of cancer → For palliation (to control pain or alleviate symptoms) → For prophylaxis (to prevent them from getting a cancer)