ANTINEOPLASTIC DRUGS

- Affecting cell survival or boosting immune system

1. ALKYLATING AGENTS
- cytotoxic effects by reacting chemically with DNA, RNA, or other cellular proteins -> most potent with cellular DNA
- can affect cells eve in the resting phase -> good for slow-growing cells (many resting phase)
- nitrogen mustards, alkyl sulfonates, nitrosoureas, triazenes, ethylenimines, alkylating-like drugs
- cell cycle-nonspecific

ACTIONS/INDICATIONS:
- Disrupts cellular mechanisms that affect DNA -> cell death
- Lymphomas, leukemias, myelomas, ovarian/testicular/breast cancers; pancreatic cancers
- Alkalytes cellular DNA -> interfering replication
- Bind with DNA molecules -> cross linking of DNA strands -> prevents separation of double-coiled DNA

THERAPEUTIC OUTCOME: eradication of malignant cells

PHARMACOKINETICS:
- A – varies; D – little is unknown; M – liver; E – urine (hepatic/nephron-toxicity)
- Teratogen

CONTRAINDICATIONS AND CAUTIONS:

- Allergies, pregnancy or lactation, bone marrow suppression (index for dosing/redosing), renal or hepatic dysfunction

COMMON DRUGS:
1. busulfan (Busulfex)– myelogenous leukemia; dosing monitored by effects on bone marrow; always push fluids to decrease toxic
renal effects; alopecia is common
2. chlorambucil (Leukeran)– lymphomas and leukemias; rheumatoid arthritis; toxic to liver and bone marrow; dosing based on bone
marrow response
3. cyclophosphamide (Cytoxan, Neosar)– lymphoma, myelomas, leukemias; hemorrhagic cystitis; alopecia
4. streptozocin (Zanosar) – metastatic cell carcinoma of the pancreas; renal and GI toxicity, infertility; use rubber gloves to avoid
drug contact – if contact occurs, wash
5. cisplatin – metastatic testicular or ovarian tumors, bladder cancers; neurotoxic, nephrotoxic, serious hypersensitivity reactions

ADVERSE EFFECTS:
- Hematological effects: bone marrow suppression, leukopenia, thrombocytopenia, anemia, pancytopenia
- GI: nausea, vomiting, anorexia,
- Hepatic and renal toxicity
- Alopecia -> effects on hair follicles
- Toxic increase in uric acid levels
- Fatigue, malaise, fever

NURSING CONSIDERATIONS:
- Amifostine (Ethyol) – cytoprotective; protects healthy cells from cytotoxic drugs (cisplatin)
- Mesna – reduce incidence of hemorrhagic cystitis
- Both use antiemetic
- Assess contraindications/vital signs/PA
- CBC, renal functions, liver functions -> adjustments/toxic effects
- Blood tests before, during and after therapy -> monitor bone marrow function
- Administer according to schedule or combination
- Hydration – to prevent toxicity
- Protect from infection -> secondary (bone marrow is suppressed)
- Small, frequent meals, oral care -> maintain nutrition
- Proper head covering -> maintain temperature, promote self-esteem, positive body image
- Provide rests
- Avoid crowded places, sick people

2. ANTIMETABOLITES
- have chemical structures similar to those of various natural metabolites that are necessary for growth and division of rapidly
dividing neoplastic cells and normal cells
- replace needed metabolites -> prevent normal cellular function
- combination therapy
- cell cycle-specific -> S phase

ACTIONS:
- Inhibits key enzymes for DNA production/ DNA and RNA synthesis -> cell death

COMMON DRUGS:
A. FLUOROURACIL (ADRUCIL, EFUDEX, FLUOROPLEX)
- palliative treatment of various GI cancers, topical treatment of cell carcinoma and actinic keratosis, breast, ovaries
- GI toxicity, bone marrow suppression, alopecia, rash; avoid occlusive dressings; wash hands after contact with drug
- poorly absorbed orally; D – well-distributed; M – liver; E – urine

B. METHOTREXATE (FOLEX, RHEUMATREX)

- leukemias, psoriasis, rheumatoid arthritis, choriocarcinoma
- hypersensitivity reactions, liver toxicity, GI complications, bone marrow suppression, increased susceptibility to infections
-well absorbed and distributed throughout the body; M – partially; E – primarily unchanged in urine
- acute lymphoblastic/lymphocytic leukemia (children); osteogenic sarcoma (bone)
- probenecid/NSAIDS/salicylates/penicillin(inc toxicity), alcohol (toxicity); co-tri (blood abnormailities)

C. THIOGUANINE
- remission induction and maintenance of acute leukemias (alone/combination)
- bone marrow suppression, GI toxicity, miscarriage/birth defects,
- Monitor bone marrow to determine dosage/redosing
- patient should be well-hydrated -> minimize hyperuricemia -> allopurinol
- M – liver; E – urine

CONTRAINDICATIONS:
- Same; ulcerative diseases may exacerbate

ADVERSE EFFECTS:
Same…leucoverin can be given to counteract adverse effects of methotrexate

3. ANTINEOPLASTIC ANTIBIOTIC
- not selective -> toxic to human cells also
- toxic to cells multiplying rapidly -> useful in certain cancers
- antimicrobials that are considered to be tumoricidal by binding with the DNA

ACTIONS:
- Binds with DNA and interferes with DNA and RNA synthesis-> inhibits protein synthesis -> preventing cell replication

COMMON DRUGS:

A. DACTINOMYCIN
- combination therapy (sarcomas and carcinomas); potentiates radiation therapy

B. DAUNORUBICIN
- first-line treatment of advanced HIV infection and associated Kaposi’s sarcoma; ALL

C. DOXORUBICIN
- leukemias and cancers, Kaposi’s sarcoma, breast, thyroid; induce regression

D. BLEOMYCIN
- palliative treatment carcinomas, testicular cancers, Hodgkin’s/non-Hodgkin’s lymphomas, effusion

E. MITOMYCIN
- adenocarcinoma of stomach and pancreas, bladder, cervix

PHARMACOKINETICS:
A – IV; M – liver; E - urine
ADVERSE EFFECTS:
- Nausea, vomiting, fever, alopecia, stomatitis, bone marrow suppression, flu-like symptoms, cardiotoxicity, hepatotoxic,
nephrotoxic

CONTRAINDICATIONS:
- Pregnancy and lactation, allergy

NURSING CONSIDERATIONS: SAME

4. MITOTIC INHIBITORS/ NATURAL PRODUCTS

- kills cells as mitosis begins; cell-cycle-specific

A. VINCA ALKALOIDS
- periwinkle plant
- cell-cycle-specific (M phase)
- vincristine, vinblastine, vinorelbine

ACTIONS: disrupt the normal function of the microtubules( -> movement of DNA) by binding to protein in the microtubules

USES: testicular, lymphomas, Kaposi’s, breast, choriocarcinoma, non-/Hodgkin’s, Wilm’s tumor, ALL

PHARMACOKINETICS: A- iv; D – well-distributed; M – liver; E – stool, little in urine

DRUG INTERACTIONS:
- Erythromycin increases toxicity
- Reduces effects of digoxin and phenytoin
- Ca channel blockers enhances accumulation -> toxicity

B. PODOPHYLLOTOXINS
- cell cycle-specific (G2 and S phase)
- etoposide, teniposide

ACTIONS: block cells at S or G2 phase/ breaks DNA strands

USES: testicular, prostate, small- cell lung, ALL,

PHARMACOKINETICS: A-moderately absorbed from GIT; D – widely distributed; M – liver; E – urine

ADVERSE EFFECTS: SAME

5. HORMONES
- some cancers are sensitive to estrogen (breasts, testes, ovaries, prostate, uterus)
- estrogen stimulates tumor to grow and divide
- block or interfere receptor sites
- fulvestrant, tamoxifen – most common

ACTIONS: exact neoplastic action is not known; known to be estrogen antagonists

USES: breast cancer

PHARMACOKINETICS: A – oral (not influenced by food); D – well-distributed; M – liver; E – stool/urine

CONTRAINDICATIONS: pregnancy, lactation, allergy, renal/hepatic dysfunction,

NURSING CONSIDERATIONS: SAME

ANTI-INFLAMMATORY AGENTS
- Block or alter the chemical reactions associated with the inflammatory response to stop one or more s/sy of inflammation
- Corticosteroids -> block inflammatory system and immune system; antihistamines-> block histamine
- Salicylates, NSAIDS, acetaminophen(paracetamol)

1. SALICYLATES
- oldest anti-inflammatory drugs; for fever, pain, inflammation
- most common analgesic (slight to moderate pain)

ACTION:
-inhibits prostaglandin synthesis that: (a) sensitize pain receptors to stimulation causing pain; (b) produces s/sy of inflammation; (c)
pyrogens by WBC/ release in the brain that causes increase in body temperature
- ASPIRIN -> inhibits platelet aggregation <- inhibits synthesis of thromboxane A 2 (vasoconstrictor and platelet aggregation inducer)

USES: mild to moderate pain, fever, inflammatory conditions (arthritis, headache, myalgia); TIA, stroke, reduce risk of death with MI;
not recommende for children (Reye’s syndrome)

PHARMACOKINETICS: A – stomach; M – liver; E – urine

ADVERSE EFFECTS:
Gastric irritation (administer with food, water or antacid), GI bleeding (test stool/emesis), toxicity (tinnitus, impaired hearing,
dimming vision, sweating, fever, lethargy, dizziness, confusion, vomiting – reduce dose/no antidote)

DRUG INTERACTIONS: NSAIDS (reduce platelet –inhibiting effects) – administer with gap; Probenecid(Salicylates inhibits excretion of
uric acid) , Warfarin, OHA, Methotrexate

CONTRAINDICATIONS:
- Allergy, bleeding abnormalities, impaired renal function, chicken pox or influenza (Reye’s), surgery/invasive procedures,
pregnancy and lactation

NURSING CONSIDERATIONS:
- Assess for contraindications
- Administer with food; administer drug as indicated
- Well-hydrate patient
- Report untoward signs and symptoms/increase knowledge

2. NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

- aspirin-like drugs;
- prostaglandin inhibitors
-blocks cyclooxygenase (COX-1 and COX-2)
- Celecoxib is a COX – 2 selective inhibitor; the rest COX -1

COMMON DRUGS AND USES:

a. Propionic Acids
> ibuprofen – OTC pain med; long-term management of arthritis, dysmenorrhea; mostly used NSAIDS
> ketoprofen – short-term management of pain
> naproxen – OTC; arthritis, dysmenorrhea

b. Acetic Acids
> diclofenac – acute, long term pain (inflammatory)
> indomethacin – oral, topical, rectal; moderate to severe pain; IV –PDA
> ketorolac – short-term management of pain; ocular itching

c. Fenamates
> Mefenamic Acid – short-term
> Piroxicam - acute and chronic arthritis
> Diflunisal – moderate pain, arthritis

d. Oxicam Derivative
> Meloxicam – juvenile arthritis, rheumatoid arthritis, osteoarthritis

e. Cyclooxygenase-2 Inhibitor
> Celecoxib – acute, long-term treatment of arthritis -> who cannot tolerate GI effects of other NSAIDs

ACTIONS: inhibition of prostaglandin synthesis; blocks COX-1 and COX-2

 - COX-1 turns to arachidonic acid into prostaglandins (needed in protecting he stomach lining, blood clotting, maintaining
sodium and water balance); COX-2: present at injury sites
- COX-2 Inhibitors affect only COX-2, not COX-1

USES: arthritis, pain, dysmenorrhea, fever

PHARMACOKINETICS: A- GIT; D – cross placenta and breast milk; M – liver; E – urine

ADVERSE EFFECTS: Gastric irritation (n/v, dyspepsia, pain) constipation –administer food, milk, water; stool-softeners, laxatives;
hydration; roughage, fruits, vegetables, grains
GI bleeding; hepatotoxicity; nephrotoxicity; rash, hives, swelling,
Others: headache, dizziness, fatigue

CONTRAINDICATIONS: same + cardiovascular dysfunction/HTN, peptic ulcer, GI bleeding,

3. ACETAMINOPHEN
- inhibits prostaglandin in CNS and blocks pain impulses in the peripheral tissue
- inhibiting heat-regulating center in the hypothalamus

USES: analgesic and pyretic; alternative to aspirin; no anti-inflammatory response

THERAPEUTIC OUTCOME: reduced pain and fever