YOUNAS MASIH NEW LIFE COLLEGE OF NURSING KARACHI

ANTI-NEOPLASTIC DRUGS

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Objectives

By the end of this session the learners will be able to, 1.Review the characteristics of normal and malignant cells.2.Explain characteristics of anti-neoplastic drugs.3.Classify anti-neoplastic drugs4.Discuss the nursing care of patients who are on anti-neoplastic drugs.5.Calculate the drug dosage for Anti-neoplastic drugs.

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Anti-neoplastic drugs

Cancer It is a term used for diseases in which abnormal cells divide without control and

are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems, this process is called metastasis.

Categories of cancerCategorized based on the functions/locations of the cells from which they originate:

•Carcinoma : skin or in tissues that line or cover internal organs. E.g., Epithelial cells. 80-90% reported cancer cases are carcinomas.•Sarcoma : bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

•Leukemia : White blood cells and their precursor cells such as the bon marrow cells, causes large numbers of abnormal blood cells to be produced and enter the blood.•Lymphoma : cells of the immune system that affects lymphatic system.

•Myeloma: B-cells that produce antibodies- spreads through lymphatic system.

•Central nervous system cancers : cancers that begin in the tissues of the brain and spinal cord.

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Cancer Therapeutic Modalities

There are traditionally (classical) following modalities for the treatment of the cancer

Surgery: 1/3 of patients without metastasis respond to surgery and radiation

Radiation: If diagnosed at an early stage, close to 50% cancer could be cured.

Chemotherapy: 50% patients will undergo chemotherapy, to remove micro metastasis. However, chemotherapy is able to cure only about 10-15% of all cancer patients

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New types of cancer treatment

Hormonal Treatments: These drugs are designed to prevent cancer cell growth by preventing

the cells from receiving signals necessary for their continued growth and division. E.g., Breast cancer – tamoxifen after surgery and radiation

Specific Inhibitors: Drugs targeting specific proteins and processes that are limited primarily

to cancer cells or that are much more prevalent in cancer cells. Antibodies:

The antibodies used in the treatment of cancer have been manufactured for use as drugs. E.g., Herceptin, avastin

Biological Response Modifiers: The use of naturally occurring, normal proteins to stimulate the body's

own defenses against cancer. E.g., Abciximab, rituxmab Vaccines:

Stimulate the body's defenses against cancer. Vaccines usually contain proteins found on or produced by cancer cells. By administering these proteins, the treatment aims to increase the response of the body against the cancer cells.

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Chemotherapy or Anti-neoplastic drugs

It is the drug that is used to eliminate the cancer cells without affecting normal tissues

(the concept of differential sensitivity).or

Chemotherapy is the use of drugs to inhibit or kill proliferating cancer cells , while leaving

host cells unharmed, or at least recoverable.

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General Rules for the chemotherapy

Adjuvant therapy: Additional cancer treatment given after the

primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include

chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy.

Neo adjuvant therapy: Treatment given as a first step to shrink a tumor

before the main treatment, which is usually surgery, is given. Examples of neo adjuvant

therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction

therapy.

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Cancer cells

These cells can be divided in to 2 categories Proliferating

Based on the DNA changes in cells, proliferating cycle of tumor cells can be divided into 4 phases

Pre-synthetic phase (Gap 1 phase or G1 phase). Cells chiefly make preparations for the synthesis of DNA.

Synthetic phase (S phase).Cells are synthesizing their DNA.

Post-synthetic phase (Gap 2 phase or G2 phase). DNA duplication has been finished and they are equally divided to the two of future sub-cells.

Mitosis phase (M Phase). Each cell is divided into two sub cells. Some of these new cells enter the new proliferating cycle, the others become non-proliferating cell

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Non proliferating

Non-proliferating cells include G0 phase cells (resting-phase cells),

G0 phase cells have proliferation ability but do not divide temporally.

When proliferating cells are suffered heavy casualties, G0 phase cells will get into proliferating cycle and become the reasons of tumor recurrence.

G0 phase cells are usually not sensitive to antineoplastic drugs, which is the important obstacle to tumor chemotherapy.

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Classification of the antineoplastic drugs

Alkylating agents,Antimetabolites,Natural products,Hormones and antagonistsMiscellaneous agents.

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Mechanisms of Antineoplastic Drugs

Most antineoplastic drugs act on the proliferating cycle of cell

(1) Destruction of DNA or inhibition of DNA duplication e.g. alkylating agents, mitomycin C(2) Inhibition of nucleic acid (DNA and RNA synthesis e.g. 5-fluorouracil, 6-mercaptopurine, methotrexate, cytarabine, etc.(3). Interfering with the transcription to inhibit RNASynthesis e.g. dactinomycin, dauoruicin, and doxorubicin

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Mechanisms of Antineoplastic Drugs

(4) Inhibition of protein synthesis e.g. vinca alkaloids, epipodophylotoxins, and paclitaxel(5) Interfering with hormone balance e.g. adrenal corticosteroids, estrogens, tamoxifen etc.

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Types of the antineoplastic drugs

(Ⅰ) Alkylating AgentsAlkylating agents act via a reactive alkyl (RCH2-CH2+ -) group that reacts to form covalent bonds with nucleic acids.There follows either cross-linking of the two strands of DNA, preventing replication, or DNA breakage.All alkylating agents are phase-nonspecific. kill rapidly proliferating cells, also kill non proliferating cellsCyclophosphamide: Most widely used in clinical therapy for treatment of cancer at present. It has no antineoplastic action outside the body and must be activated in the liver

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(Ⅱ) Antimetabolites

It acts mainly on the S phase cells. has a serious myelo suppression

Example:5 FU, Methotrexate

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(Ⅲ) Natural Products

The major classes of natural products includeAntibiotics( Antitumor antibiotics)Vinca alkaloids Biologic response modifiersEnzymes Epipodophyllotoxins Taxanes

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Antibiotic antineoplastic agents

Antibiotic antineoplastic agents: Damage DNA in cycling and non cycling cells

Example: Dactinomycin (actinomycin D)This drug binds no covalently to double-

stranded DNA and inhibits DNA-directed RNA synthesis.

Dactinomycin is a phase-nonspecific agent, but it is more active against G1 phase cells.

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Vinca (plant) alkaloids

Vincristine and vinblastine are alkaloids derived from the periwinkle plant.

interfere with the assembly of spindle proteins during mitosis..

Act in M phase to inhibit mitosis, blocking proliferating cells as they enter metaphase.

Both can cause bone marrow suppression and neurotoxicity

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(Ⅳ) Hormones and antagonists

Adrenocortical steroids to inhibit the growth of cancers of lymphoid tissue and blood.

Estrogen antagonists ( tamoxifen ) is indicated for breast cancer.

Estrogen is used for prostatic cancer

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(Ⅴ) Miscellaneous agents

Hydroxyurea inhibits ribonucleotidereductase. inhibition of DNA synthesis.

It is specific for the cells of S phaseThe major adverse effect of this drug is bone

marrow depression.

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Principles of combination therapies

1. Select drugs according to their phase specific characteristics2. Combinations of antineoplastic drugs with different action mechanism3. Combinations of antineoplastic drugs with other therapies4. Select drugs according to antineoplastic range (spectrum)5. Use right dose

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LIMITATIONS OF CYTOTOXIC AGENTS

There are a number of problems with the safety profile and efficacy of chemotherapeutic agents

These affect rapidly dividing cells so do not specifically target cancer cells in the resting phase.

They also only influence a cell’s ability to divide and have little effect on other aspects of tumor progression such as tissue invasion, metastases or progressive loss of differentiation.

cytotoxic are associated with a high incidence of adverse effects

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Side effects

The most notable examples include Bone marrow suppression, Alopecia, Mucositis,Nausea and vomiting.Skin color changesBody acheDirreahea

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Nursing care of the patients with chemotherapy

Induction chemotherapy: chemotherapy given to induce a remission.Consolidation chemotherapy: chemotherapy given once a remission is achieved to sustain a remission.Maintenance chemotherapy: chemotherapy given after an initial chemotherapy course to prolong a response.Palliative chemotherapy: chemotherapy that is given specifically to address symptom management.First line chemotherapy: chemotherapy first used for treating cancer that has metastasized.Second line chemotherapy: chemotherapy given when a disease has recurred or the patient no longer responds to first line chemotherapy.Third and fourth line chemotherapy: chemotherapy given when a disease has recurred or the patient no longer responds to second and third line chemotherapy

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Nursing care of the patients with chemotherapy

Following are the nursing management and care of the patient who is receiving chemotherapy

Pre chemotherapy teaching of the patient , that includes

(1). Teaching of side effects(2). Prevention (3). Diet (4). Regimen and cycles of the chemotherapyDecrease the level of anxiety of the patient

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Nursing care of the patients with chemotherapy

Proper I/V cannulation(1). Proper site and side selection (mastectomy). (2). Proper vein selectionHydration teachings and checking of the

patients(1). Pre hydration (2). Post hydration(3). Urinary output Keep patient under observation Check for I/V flow

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Nursing care of the patients with chemotherapy

Check for signs of extravasationsCheck for hemorrhage and bleedingCheck CBC ( RBC, WBC, Plt),Preventions (gum bleeding, urinary retention,

proper diet and fluid intake )Nausea and vomiting reducing strategiesTeachings to increase the dietary intake

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Extravasations

Extravasations has been termed “a dreaded complication of chemotherapy. Left untreated, vesicant chemotherapy extravasations have the potential to cause tissue necrosis, functional impairment, and permanent disfigurement. Surgical intervention and wound care often are required

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Extravasations

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Extravasations

Management of the patients with extravasations1.Ask patient and other staff to keep on eye on

the area which is cannulated for chemotherapy 2.If signs of extravasations occurs immediately

stop the medicine3.common symptoms of vesicant extravasations

are redness and swelling and discomfort may or may not be present,10 application of a transparent dressing secures the IV device

4.A blood return from the IV device should be obtained before administering a vesicant

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Extravasations

6. Apply topical heat or cooling (Local cooling using ice packs or cold gel packs whereas, Local warming (dry heat) is indicated for non-DNA-binding vesicant extravasation).

7. Antidotes and treatments (Local injection of sodium thiosulfate is the recommended antidote, Local injection of hyaluronidase)

8. Document the event9. Inform the supervisor or manager about the event

and explain to the patient and family10. Monitor the site for further complications 11. Don’t use the area for chemotherapy

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References

Cancer Chemotherapy. (2010, December 31). Retrieved from http://www.uic.edu/classes/pcol/pcol331/Antineoplastic%20Agents%202011%20Dental%20MARCH-1.pdf

Kishore", W. (2011, March 23). Pharmacology of Antineoplastic Agents. Retrieved from http://pharmacology.xjtu.edu.cn/ppt/Anticancer.pdf

Schulmeister, L. (2010). Preventing and Managing Vesicant Chemotherapy Extravasations. THE JOURNAL OF SUPPORTIVE ONCOLOGY, 8(5), 212-215.

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