Pharma Anti Neoplastic

8/6/2019 Pharma Anti Neoplastic

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CANCER

Results from damage to the DNA within the cell

DNA is the genetic substance in the body cells

and transfers information necessary for the

production of enzymes and protein synthesis Develops when some of the genes in a normal

cell become damaged or lost (mutation)


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CANCER CELLS ARE

CHARACTERIZED BY: Unregulated growth

Lack of differentiation

Spread to other body cells and organs


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CELL CYCLE

G1= presynthesis that prepare for DNA

synthesis

S= DNA synthesis occurs

G2= post synthesis phase in which the cellis prepared for mitosis

M= mitosis/ cell division occurs

G0= resting phase


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ANTICANCER DRUGS

Also called Cancer ChemotherapeuticAgents orAntineoplastic Drugs

Cause cancer death by interfering with cellreplication

Chemotheraphy

May be used as the sole treatment of cancer or in conjunction with other modalities

Combination therapy has proveneffective in curing some cancers(Leukemia, Hodgkins disease, Wilmstumor)


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When cancer cannot be cured, anticancer

drugs may be given to control the disease

for a period of months to years

If the cancer can no longer be controlled,chemotherapy may be used to relieve

symptoms associated with the disease


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CELL-CYCLE NONSPECIFIC

Act during any phase of the cell cycle

Also called Cell-cycle Independent

CELL-CYCLE SPECIFIC

Exert their influence during a specific

phase of the cell cycle

Also called Cell-cycle Dependent

Most effective against rapidly growingcancer cells


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TWO FACTORS THAT PLAY A MAJOR

ROLE IN THE RESPONSE OF CANCER

CELLS TO ANTICANCER DRUGS

GROWTH RATE (DOUBLING TIME) Time it takes for a cancerous tumor to double in size

GROWTH FRACTION

The number of cells proliferating within the tumor


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GENETIC, INFECTIVE,

ENVIRONMENTAL ANDDIETARY INFLUENCES

Cancers that have a genetic influence include breast,

ovarian, endometrial, colon and lung cancers,

retinoblastoma and malignant melanoma


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Environmental

Tobacco

Cancer of the lung, larynx, bladder,

kidney, colon, cervix, stomach,

pancreas, or breast Asbestos

Lung cancer

Benzene

Acute myelogenous leukemia Vinyl Chloride

Sarcoma


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Arsenic

Cancer of the lung, skin, sarcoma

Ionizing Radiation

Leukemia, cancer of the thyroid, breast

Ultraviolet Rays

Skin cancer

Aflatoxin

Liver cancer


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Infective

Herpes Simplex 2 Virus (Genital Herpes)

Cancer of the cervix

Hepatitis B and Hepatitis C Virus

Cancer of the liver

Epstein-Barr Virus (a cause of infectious

mononucleosis)

Burkitts lymphoma, nasopharyngeal

cancers Human Papilloma Virus (HPV)

Cancer of the cervix


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Human T-Cell Lymphotrophic Virus

T-cell leukemia

Helicobacter Pylori

Cancer of the stomach


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Diet

Animal fat

Cancer of the colon, rectum, breast,

uterus, prostate, ovary

Heterocyclic Amines (found in somesmoked meats)

Cancer of the stomach, colon, rectum,

pancreas, breast

Alcohol Cancer of the mouth, throat,

esophagus, liver, breast


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Anticancer drugs

Not selective

Affects cancer and normal cells

Side effects related to toxic effects onnormal cells

Effective because normal cells are ableto repair themselves and continue togrow

Cancer cells are less able to do so Side effects of chemotherapy are often

temporary


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Chemotherapy

Administered systematically for cancer

that has spread to other parts of the

body For tumors in multiple sites

For tumors too large to be removed

through other means (surgery)


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Intravenous (IV) infusion Most common route of chemotherapy

Other routes

Oral Intramuscular

Subcutaneous

Intraperitoneal

Intrathecal

Intracavitary Intravesical

Intraarterial

topic


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Adjuvant therapy

Treated with surgery first

Followed byby chemotherapy to eliminate

residual tumor cells (microscopicmetastases) that remain in the body

E.g. breast cancer, colon cancer


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Neoadjuvant chemotherapy

Help shrink large tumor so it can be

surgically removed

Palliative chemotherapy Relieve symptoms associated with

advanced disease (pain)

Improve quality of life


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Length of treatment is determined by

Type and extent of malignancy

Type of chemotherapy given

Expected side effects of drugs Amount of time that normal cells need

to recover


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Duration, frequency, and number of cycles

of chemotherapy are based on

Type and size of tumor

Whether disease has spread to otherareas of the body (metastasis)

Condition of client


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Dose dense chemotherapy

Interval between successive doses of

chemotherapy is shortened

Improved survival in some cancerpatient


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Multi-drug resistance (MDR)

Malignant tumors often develop

resistance to chemotherapeutic agents.

Cells may mutate and become resistant Gene amplification

Gene produces copies of itself

Leads to overproduction of protein that

makes chemotherapy drug lesseffective.


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P-glycoprotein (P-gp)

Pumps the chemotherapy out of the

cells before it can be effective


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Combinations of anticancer agents

More effective tumoricidal activity

Most effective when it is able to kill cells

in all phases of the cell cycle Often combine CCS (cell-cycle specific

drugs) and CCNS (cell-cycle

nonspecific drugs)

drugs resistance destruction of cancer


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BONE MARROW

ANEMIA (low RBC count)

Assess for fatigue, BP, RR, HR,oliguria, mental status changes

Asses cyanosis

Plan rest periods

Administer oxygen

Elevate HOB (breathing)

Treated with ferrous sulfate andinfusions of RBCs

Administer Erythropoietin (stimulateproduction of RBCs)


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NEUTROPENIA (low WBC count)

Susceptible to infections

Avoid visitors with colds or infection

Report to HCP: fever, chills, upperrespiratory infections

Wash hands before and after

Monitor or of temperature

temperature: infection 38.3C: report to HCP

Monitor WBC


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THROMBOCYTOPENIA (low platelet

count)

Report signs of low platelet count

(petechias, bruising, bleeding ofgums, epistaxis)

Avoid medications that promote

bleeding (aspirin)

Avoid invasive procedures

(injections, indwelling catheters,

rectal temperature)

Monitor platelet count


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N/V

Antineoplastic drugs stimulate CT2

(chemoreceptor trigger zone) that

can cause n/v Causes of n/v

Irritation of GI tract

Radiation to chest, abdomen or

brain Anxiety

Constipation

Pain

Electrolyte imbalance


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DIARRHEA Three types of diarrhea:

1. OSMOTIC: absorption defects

2. SECRETORY: bacterial infection

3. EXUDATIVE: secondary to chemotherapy Asses normal bowel habits

Monitor electrolyte imbalances anddehydration

Teach to eat small frequent fruits and

vegetables Limit caffeine, carbonated drinks, spicy, fattyfoods, salty foods and whole grain

Avoid very hot or very cold foods (stimulatesperistalsis)

Monitor intake and output

Administer anti-diarrheal medications


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MUCOSITIS (stomatitis)

Occur 2-14 days after initiation

Assess taste changes, tissueswelling, redness, pain, dry mouth,white patches

Avoid mouthwash with alcohol

Use soft toothbrush

Offer ice pops or ice chips (relieve

pain) Assess intake and output

Treatment

Frequent mouth rinses

Antibiotics


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ALOPECIA

Not all chemotherapeutic agents

cause hair loss

Hair on all areas of the body isaffected

Discuss potential hair loss and ways

to address problem (wigs, scarves,

hats, turbans)

Hair growth after completing

therapy. Texture will change.


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Adriamycin


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Was approved by FDA over 30 years ago and

is used in the treatment of many types of

cancer. It is an important prototype drug which has

led to the development of many analogs(epirubicin (Ellence), idarubicin (Idamycin))

However, it has severe cardiotoxic effects andmust be given with caution


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Administered IV and metabolized inthe liver to active and inactivemetabolites

Initial phase is 12 minutes

Intermediate phase is 3.5hours

Final phase is 30 hours


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Is prescribed in combination with other anti-

cancer agents for the treatment of cancer of

the: breasts

ovaries

lung bladder

leukemias & lymphomas


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Recipients of this drug are limited to a

maximum lifetime dose of 550 mg/m2

which may be lowered for individuals

who have :

preexisting cardiac problems

use cardiac toxic medications

Older in age

Who have received radiation to the

chest


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CARDIAC FUNCTION of potential

recipients is assessed prior to treatment

with doxorubicin DEXRAZOXANE (ZINECARD) is a

cytoprotective agent that may be given

to help prevent cardiac toxicitiesassociated with doxorubicin

adminstration


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Anorexia Nausea/Vomiting Diarrhea Rash

Alopecia May cause flare reaction


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Nausea and vomiting are dose-related

and may begin 1-3 hours after

administration Causes discolored urine (pink to red)for

up to 48 hours

May cause radiation recall topreviously irridiated skin


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Esophagitis

AnemiaHyperpigmintation of nails,

tongue and oral mucosa (esp in

African Americans)Drug is teratogenic, mutagenic

and carcinogenic


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Monitor IV site frequently. Give drug

through a large bore, quickly running IV

infusion Administer antiemetic 30 to 60 minutes

before chemotherapy as prescribed by

the physician Monitor for changes in urine color


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Plan small, frequent meals Administer prophylactic antibiotics

to prevent infection as prescribed bythe physician

Offer analgesics for pain asprescribed by the physician


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Maintain strict medical asepsis

during dressing changes andinvasive procedures

Monitor fluid intake and output

and nutritional intake


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AlkylatingDrugs


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One of the largest groups of anticancer drugs

Cause cross-linking of DNA strands, abnormal

base pairing, or DNA strands breaks, thusprevent the cell from dividing

Belong to the CCNS category and kill cells in

multiple phases of cell cycle

Most effectiveMost effective against cells in Go phase Groups:

Mustard gas derivatives

Alkysulfonates

Ethylenimines

Hyadrazines and Triazines

Nitrosoureas they can cross the blood brain barrier

Metal salts


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MechlorethamineMechlorethaminefirstfirst alkylatingalkylating drugdrug

introducedintroduced for cancerfor cancer

BecameBecame availableavailable forfor clinicalclinical useuse duringduring

WorlWorl WAR IIWAR II

ItIt isis administeredadministered as part of theas part of the

chemotherapychemotherapy regimenregimen toto treattreat HodgkinsHodgkins

diseasedisease

severesevere vesicantvesicantthatthat cancan cause tissuecause tissue

necrosisnecrosis ifif itit infiltritaesinfiltritaes to the tissueto the tissue

PrescribedPrescribed throughthrough IVIV

The pxThe px shouldshould bebe wellwell hydratedhydrated toto preventprevent

hemorrhagichemorrhagic cystitiscystitis

Cyclophosphamide (Cytoxan)


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Side Effects

Nausea

Vomitting

Hemorrhagic cystitis

Alopecia

Anemia

Leukopenia

Thrombocytopenia

Bone marrow suppression(anemia,leukopenia,thrombocytopenia)

Secondary malignancies

Sterility


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pharmacokinetics

This drug is well absorbed from the GI

tract

Its half life is moderate

Moderately protein-bound

Metabolized by the liver

Less than 50% is excreted unchanged

in the urine


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pharmacodyanamics The onset of action begins 2 3 hours

Therapeutic effect may take several

days


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PLANT ALKALOIDSPLANT ALKALOIDS


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MITOTIC INHIBITORSMITOTIC INHIBITORS

Mitotic inhibitors are plant alkaloids and

other compounds derived from natural

products that are CCS and block cell

division at the M phase of the cell cycle.

CellCell--cycle specific (CCS) agentscycle specific (CCS) agents

Chemotherapy agents that negativelyChemotherapy agents that negatively

affect cancer cells when they are activelyaffect cancer cells when they are actively

dividing.dividing.

ViVi Alk l idAlk l id


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VincaVinca AlkaloidsAlkaloids

-Vinblastine

[Velban]-Vincristine

[Oncovin]

- Vinorelbine

[Navelbine]

They are obtained from the

peri-winkle plant.


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AntimicrotubulesAntimicrotubules ororTaxanesTaxanes

groupgroup

Docetaxel [Taxotere]

Paclitaxel [Taxol]

They were originally procured

from the needles and bar of the

yew tree.


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ADVERSE REACTIONS TOADVERSE REACTIONS TO


Leukopenia

Allergic reactions

Partial-to-complete alopecia

Constipation N/V

Diarrhea

Phlebitis

The plant alkaloids damage peripheralThe plant alkaloids damage peripheral

nerve fibers and may cause reversiblenerve fibers and may cause reversible

or irreversible neurotoxicity.or irreversible neurotoxicity.


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SignsandsymptomsofSignsandsymptomsof

NEUROTOXICITYNEUROTOXICITY

- decrease in muscular strength

- numbness- tingling of fingers and toes

(stocking/glove syndrome)

- constipation

- motor instability


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OtheradverseeffectsofOtheradverseeffectsof


Loss of deep tendon reflexes

Muscle weakness

Joint pain and bone marrow depression


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VINCRISTINE [ONCOVIN]VINCRISTINE [ONCOVIN]

Developed from the periwinkle plant, was

originally approved by the FDA in the

1960s to treat Wilms tumor in children.

PharmacokineticsPharmacokinetics

--given IVgiven IV

--halfhalf--life is between 5 minutes and 85life is between 5 minutes and 85

hourshours

--primarily proteinprimarily protein--bound: 75 %bound: 75 %

--metabolized by livermetabolized by liver


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SideeffectsSideeffects

Peripheral neuropathy

Loss of deep tendon reflexes

Phlebitis

Constipation

Cramps

N/V

Muscle weakness

Reversible alopecia


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Adverse ReactionsAdverse Reactions

Sensory loss

HypotensionHypotension

Visual disturbancesVisual disturbances

PtosisPtosis HyponatremiaHyponatremia

HyperuricemiaHyperuricemia

Severe local reaction withSevere local reaction with extravasationextravasation

Fever Fever


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ContraindicationContraindication

-Fatal if given intrathecally

-Do not give to patients receiving

radiation therapy through ports into theliver

-Do not give to patients with

Charcot-Marie-Tooth Syndrome

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