ANTITUMOR ANTIBIOTICS

ANTITUMOR ANTIBIOTICS

·         Interferes with DNA synthesis by binding DNA; prevents RNA synthesis

·         Indication:

o    Target malignancies: Leukemias, Neuroblastoma, Nephroblastoma, breast caner, ovarian cancer, thyroid cancer and lung cancer

·         Contraindication:

o    Lung disease, renal and hepatic disorders, ulcers, and gastrointestinal disease

Example:

bleomycin (Blenoxane®)

dactinomycin (Actinomycin D®, Cosmegan®)

daunorubicin (DaunoXome®, Cerubidine®)

doxorubicin (Adriamycin®)

idarubicin (Idamycin®)

mitomycin (Mutamycin®)

mitoxantrone (Novantorone®)

plicamycin (Mithracin®)

valrubicin (Valstar®)

Side Effects:

·         Bone marrow suppression

·         Nausea and vomiting

·         Alopecia

·         Anorexia

·         Vesication

·         Daunorubicin (DaunoXome), Idarubicin (Idamycin) and Doxorubicin (Adriamycin): cardiotoxicity

·         Bleomycin (Blenoxane): pulmonary toxicity

·         Plicamycin (Mithracin): affects bleeding time

Nursing Considerations:

ü  Assess vital signs and temperature for signs of infection.

ü  Withhold medication if platelet count is <75,000 cells/µL or WBC is <4000 cells/ µL and notify the physician.

ü  Monitor ECG; assess for arrhythmias, gallops and CHF (during dactinomycin [Actinomycin D], daunorubicin [DaunoXome, Cerubidine], Doxorubicin [Adriamycin] therapy.

ü  Monitor CBC with differential, BUN and uric acid.

ü  Assess pulmonary function studies (during Bleomycin [Blenoxane] therapy).

ü  Assess for bleeding; check stool for occult blood. Avoid use of aspirin, anticoagulants and thrombolytic agents (during Plicamycin [Mithracin] therapy).

ü  May see delayed cardiotoxicity months to years after administration of doxorubicin.

ü  To prevent heart failure related to doxorubicin, do not administer more than 550 mg/m²  in a lifetime

ü  Evaluate hydration and nutrition status.

ü  Monitor IV site for vesication.

ü  Instruct oral care for stomatitis.

ü  Teach care for hair loss.

MITOTIC SPINDLE POISONS (Mitotic Inhibitors, Vinca Alkaloids)

·         Arrests metaphase by inhibiting mitotic tubular formation (spindle); inhibit DNA and protein synthesis

·         Indication:

o    Target malignancies: Leukemias, Hodgkin’s and Non-Hodgkin’s lymphomas,lymphocytic and histocytic lymphoma, neuroblastoma, nephroblastoma, Kaposi’s sarcoma, advanced testicular cancer and unresponsive breast cancer 

·         Contraindication: Cardiovascular, hepatic, nerve, and muscle disease

Example:

Plant Alkaloids o    etoposide (VePesid®) o    teniposide (Vumon®) o    vinblastine (Velban®) o    vincristine (Oncovin®) o    vinorelbine (Navelbine®)

Taxanes o    paclitaxel (Nov-Onxol®, Taxol®, Paclitaxel Novaplus®) o    docetaxel (Txotere®)

Side Effects:

·         Alopecia

·         Hoarseness

·         Ptosis

·         Anorexia, nausea and vomiting

·         Stomatitis

·         Hyperuricemia

·         Constipation, paralytic ileus

·         Vinblastine(Velban®): bone marrow suppression

·         Vincristine (Oncovin®): Neorotoxicity/ neuropathies

·         Taxanes: Bradycardia, hypersensitivity reactions and neuropathies

·         Areflexia

Nursing Considerations:

ü  Assess vital signs.

ü  Monitor CBC with differential.

ü  Assess neuromuscular function.

ü  Evaluate gastrointestinal function; manage constipation.

ü  Administer antiemetics prn as ordered.

ü  Monitor eyes for ptosis; monitor for hoarseness.

ü  Teach ways to manage hair loss.

HORMONAL AGENTS

·         Binds to hormone receptor sites that alter cellular growth; block binding of estrogens to receptor sites (antiestrogens); inhibit RNA synthesis

·         Indication:

o    Target malignancies: Advanced breast and prostate cancer

·         Contraindication:

o    Pregnancy, hepatic and renal disease, osteoporosis, hypertension, hypercholesterolemia

Example:

diethylstilbestrol (DES, Stilphostrol®)

letrozole (Femara®)

raloxifene (Evista®)

tamoxifen (Nolvadex®)

goserilin acetate (Zoladex®)

Testosterone

medroxyprogesterone (Depo- Provera®)

asparaginase (Elspar®)

mitotane (Lysodren®)

megestrol acetate (Megace®)

Side Effects:

·         Hypercalcemia

·         Hypertension

·         Jaundice

·         Increased appetite, weight gain

·         Masculinization

·         Feminization

·         Sodium and fluid retention

·         Hot flashes

·         Vaginal dryness

·         Nausea and vomiting

·         Asparaginase (Eslpar): impaired pancreatic function

·         Mitotane (Lysodren): Hemorrhagic cystitis, hyperuricemia and hypercholesterolemia

·         Tamoxifen (Nolvadex): Edema, hypercalcemia, elevated cholesterol and triglyceride levels, decreased effects of estrogen

·         Diethylstilbestrol (DES, Stilphostrol):

§  Female: Fluid retention, feminization and uterine bleeding

§  Male: impotence and masculinization

Nursing Considerations:

ü  Monitor vital signs.

ü  Administer diuretics prn as ordered.

ü  Monitor for bleeding.

ü  Monitor electrolytes, uric acid and cholesterol levels.

ü  Monitor pancreatic function.

ü  Explain reason for sex characteristic alterations.

ü  Provide patient teachings for managing hot flashes.

HIV and Aids

·         Acquired Immune Deficiency Syndrome (AIDS) is a chronic, life threatening condition caused by Human Immunodeficiency Virus (HIV).

·         Characterized by generalized dysfunction of the immune system making individuals susceptible to opportunistic infections & tumors.

·         Pneumocystis carinii pneumonia: most common opportunistic infection. 

·         Incubation period estimates range from 6 months to 9 years.

Pathophysiology:

·         HIV binds with CD4+T cells and replicates by generating a DNA copy by reverse transcriptase.

·         HIV causes AIDS by destroying CD4+T cells which leads to a weak immune system allowing opportunistic infections.

Epidemiology:

·         5^th leading cause of death among ages 25-44 years in the US

·         In the US, it is common among African American, Hispanics and Caucasians. (CDC)

·         Most HIV infections occur in men due to homosexual contact but the incident is already increasing among women who engage in unprotected sexual activities.

Mode of Transmission:

·         Horizontal transmission: Sexual contact (oral, vaginal, anal sex); parenteral exposure to blood or body fluid containing visible blood.

·         Vertical (perinatal) transmission: HIV infected pregnant woman passes the infection to fetus during pregnancy, delivery or breastfeeding.

Clinicl Stages of HIV/AIDS	Signs & Symptoms
Stage I.         Asymptomatic/Primary    HIV infection	Flu-like symptoms ü  Fever ü  Myalgia ü  Persistent generalized lymphadenopathy ü  Headache
Stage II.	ü  Person may experience outbreak of herpes zoster ü  Recurrent respiratory tract infection ü  Chronic diarrhea for longer than 1 month
Stage III.	ü  Integumentary problems ü  Gynecological problems
Stage IV.	ü  HIV wasting syndrome ü  Development of opportunistic infections

Diagnostic Exams:

§  AIDS is present if there is 2 positive results of ELISA confirmed with positive result on Western blot assay.

§  Enzyme –linked immunosorbent assay (ELISA)/ Enzyme immunoassay (EIA)

o Identifies antibodies directed specifically to HIV.

o Useful in children older than 18 months.

§  Western blot assay

o Confirm HIV infection

                        Useful in children older than 18 months

§  Viral load tests: Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR) & Nucleic Acid Sequence-Based Amplification (NASBA)

o < 10,000 copies/mL = low risk AIDS

o > 100,000 copies/mL = High risk for AIDS. (+) viral activity

o Measures HIV RNA in the plasma.

o Measures response to treatment.

o RT-PCR detects HIV in high risk seronegative people before antibodies are measurable, screen neonates, & confirm + EIA result.

§  CD4/CD8 Ratio

o Helper/ suppressor ratio = degree of immune suppression.

o CD4 count of <200/mm3: indicates AIDS

o Normal values depend on age (ratio 0.9 to 3.7 in adults).

§  p24 antigen

o 2 or more positive results are diagnostic for HIV infection

o Used o detect HIV antigen in children younger than 18 months.

§  Nonspecific markers of disease progression: blood counts, albumin levels & ESR

§  Skin biopsy, serum chemistries and imaging studies are indicated depending on organ/system involvement & disease progression.

Treatment:

·         There is no cure; prevention is the only key to control.

·         Highly Active Antiretroviral Therapy (HAART): reduces the number of HIV particles in the blood stream as measured by viral load test.

-    Combination of three (3) drugs belonging to 2 types of antiretroviral agents.

-    Side effects include: lipodystrophy, dyslipidaemia, diarrhea, insulin resistance, an increase in cardiovascular risks and birth defects.

-    n.b: Patient problem with HAART: non-adherence with complex administration leads to drug resistance development.

·         Antiretroviral drugs: inhibit the growth and replication of HIV at various stages of its life cycle.

Types/Classes:

1.        Nucleotide reverse transcriptase inhibitors/NtRTIs & Nucleoside analogue reverse transcriptase inhibitors/NRTIs (“nukes”): inhibit the replication of an HIV enzyme called reverse transcriptase.

E.g.  idovudine (Retrovir^®) [formerly called AZT azidothymidine], lamivudine (Epivir^®) didanosine (Videx^®), zalcitabine (Hivid^®), stavudine (Zerit^®) and abacavir (Ziagen^®)

2.        Protease inhibitors (PIs): interfere with an enzyme known as HIV protease. This causes HIV particles in your body to become structurally disorganized and noninfectious.

e.g atazanavir/ATV (Reyataz^®), darunavir/DRV (Prezista^®), Fosamprenavir/FPV (Lexiva^®), lopinavir + ritonavir (Kaletra^®), saquinavir/SQV (Invirase^®), tipranavir/TPV (Aptivus^®)

3.        Non-nucleoside reverse transcriptase inhibitors (NNRTIs): bind directly to the enzyme reverse transcriptase. E.g efavirenz (Sustiva^®, Stocrin^®);  nevirapine (Viramune^®); delavirdine (Rescriptor^®); etravirine (Intelence^®)

1.        Fusion inhibitors (entry inhibitors): suppress resistant strains of HIV. e.g maraviroc (Selzentry^®), enfuvirtide (Fuzeon^®)

2.        Integrase inhibitors: aims to treat those who become resistant to other treatments. e.g raltegravir (Isentress^®)

·         CCR5 antagonists: new class of drugs used to treat a particular type of HIV infection called CCR5-tropic HIV-1

E.g. maraviroc (Selzentry^®)

Side effects: liver problems, postural hypotension, inflammation response.

·         Oral Progesterone (Megace^®, Winstrol^®): stimulate appetite thereby assisting with the treatment of weight loss (HIV Wasting Syndrome)& loss of taste perception

·         For disease progression: Antibiotic therapy, chemotherapy, analgesic, antiemetic, antifungal & appetite stimulants.

·         Supportive care for chronic illness associated with HIV infection: O2 therapy, IV fluid, electrolyte replacement and mechanical ventilation (end stage AIDS).

Prevention:

If HIV negative:

·         Know the HIV status of your partner.

·         Provide client education regarding safe & protected sex:

o Latex condom: vaginal or anal intercourse

o Dental dam: used for oral contact with the vagina or rectum

o Avoid sexual contact with multiple partners.

·         Consider male circumcision

·         Use sterile needle & avoid needle sharing.

·         Be cautious about blood products.

·         Get routine HIV testing

If HIV positive:

·         Follow safe sex practices.

·         Tell your sexual partner that you have HIV.

·         Don’t share needles or syringes.

·         Don’t donate blood or organ.

·         Don’t share razors, toothbrush, sex toys or blood contaminated articles.

·         Drug users interested in drug treatment programs must be referred.

·         Get immediate medical care if pregnant.

·         Don’t breastfeed the infant.

·         TB testing 

For health workers:

·         Standard precautions: apply to blood, body secretions & excretions.

Nursing Interventions:

·         Use of universal precautions for all clients regardless of diagnosis.

·         Provide ongoing coordination of health care team to afford client the best possible assistance.

·         Provide emotional support, counseling and referral to support group.

·         Protect the client from secondary infections; assess for early signs and report for treatment.

·         Maintain client advocacy and confidentiality.

·         Refer to dietician to analyze nutritional requirements & make recommendations to maintain ideal body weight.

·         Provide high-caloric, high protein diet to prevent weight loss.

·         Encourage intake of foods rich in vitamins A, C & E.

·         Educate on:

o    Importance of compliance to long-term treatment regimen.

o    Stress the need for follow-up check-up & diagnostic tests to monitor response to treatment & disease progression.

Discuss life issues with the client & support system members as disease progresses & prognosis worsens