#1 - cardiovascular disease

#2 - Cancer

#3 - chronic lower respiratory diseases

The definition of Cancer:

normal cells become neoplastic due to DNA or RNA alterations (mostly mutations) leading to abnormal __________

hereditary - gene mutations passed on from generation to generation

carcinogens - agents that induce DNA alterations in "cancer genes"

environmental carcinogens: ionizing radiation (leukemia, thyroid, breast, lust) and non-ionizing radiation (skin cancer)

UV-C

(has the shortest wavelength, and the shorter the wavelength, the higher the energy)

surgery - removal of tumor mass

radiation therapy - exposure of tumor mass of whole body to ionizing radiation to reduce tumor burden

chemotherapy - administration of chemicals to reduce tumor burden

combined modality therapy

DNA synthesis inhibitors

DNA alkylating drugs

DNA intercalating drugs

Mitotic inhibitors

topoisomerase inhibitors

monoclonal antibodies

tyrosine kinase inhibitors

hormonal modulators

acquired resistance results from genetic mutations or abnormal gene expression which in turn causes:

drug efflux pumps

decreased affinity or overexpression of target proteins

decreased drug activation

increased drug inactivation

altered expression of proapoptotic or antiapoptotic proteins

N/V

organ system toxicity

suppression in bone marrow activity that leads to a deficiency in the production of WBCs, RBCs and/or platelets is called

WBC deficiency is termed and results into

RBC deficiency is termed and results into

platelet deficiency is termed and results into

myelosuppression

WBC def - leukopenia --> resulting in infections

RBC def - erythrocytopenia --> resulting in anemia

platelet def - thrombocytopenia --> resulting in bleeding

there are no current methods to PREVENT myelosuppression, but recovery time from myelosuppression can be decreased by administration of recombinant hematopoietic growth factors:

epoetin

filgrastim

sargramostim

what is the MOA that causes the nausea and vomiting after taking antineoplastic drugs

which agents stimulate the most N/V

antineoplastic drugs stimulate the chemoreceptor trigger zone in the medulla which causes the pt to experience N/V

cisplatin and carmustine

5-HT3 antagonists (ondansetron)

Tachykinin receptor antagonist (aprepitant)

corticosteroids

D2 receptor blocker (metoclopramide)

cannabinoid receptor agonist (cannadinoids)

(the first three are the most commonly used)

doxorubicin

and other anthracyclines

bleomycin

bisulfan

carmustine

cyclophosphamides

dexrazoxane

mesna

mannitol and sodium thiosulfate

corticosteriods

antifolates: methotrexate

Pyrimidine antagonists: fluorouracil (5-FU)

methotrexate is an antifolate, DNA synthesis inhibitor

and its structure resembles folic acid and therefore inhibits dihydrofolate reductase enzyme (the enzyme that folate binds to to become THF, which is required for DNA synthesis)

what is the antineoplastic combination CMF

and what cancer(s) is it used for

cyclophosphamide

methotrexate

5-FU

CMF is used to treat breast cancer

methotrexate is used for the treatment of what cancers

what are it's non-cancer uses

breast cancer (CMF)

choriocarcinoma

acute lymphatic leukemia

non-cancer uses:

rheumatoid arthritis

psoriasis

severe oral ulceration (stomatitis)

kidney damage (when used long term, ie psoriasis and RA)

bone marrow suppression

GI toxicity

hepatotoxicity (long term use, same as kidney damage)

what drug can you give along with methotrexate to help prevent the severe adverse effects of the methotrexate

and how does it work

leucovorin (folinic acid)

the drug is providing the body with low doses of folic acid via selective rescue of normal but not tumor cells, because the tumor cells require a greater damand for folic acid and therefore it wouldn't be enough to keep these cell alive

it is a pyrimadine antagonist, DNA synthesis inhibitor

it is an analog of uracil, it undergoes a series of biotransformation reactions and binds to and inhibits thymidylate synthase and incorporates into DNA and RNA strands causing chain termination

Colorectal cancer (FOLFOX)

Breast cancer (CMF)

actinic keratosis and basal cell carcinoma (topically)

what is the antineoplastic combination of FOLFOX

and what cancers is it used for

FOL: leucovorin (FOLinic acid)

F: 5-FU

OX: oxaliplatin

FOLFOX combo is used for colorectal cancer

List the maintypes of DNA alkylating agents

and what is the MOA of DNA alkylating agents

nitrogen mustards (chyclophosphamide)

nitrosoureas (carmustine)

platinum compounds (cisplatin)

DNA alkylating agents cross link DNA strands by forming covalent bonds between alkyl groups of the drug and DNA base, resulting in DNA denaturation that causes the strand to break, and in the end this activates the cellular DNA repair machinery leading to apoptosis

nitrogen mustards are what type of antineoplastic

what is/are the main nitrogen mustards

nitrogen mustards are a type of DNA alkylating agents

cyclophosphamide is the main nitrogen mustard (as well as ifosfamide)

CLL

non-hodgkin's lymphoma (CHOP-R)

Breast cancer (CMF)

Lung cancer (CAV)

what is the antineoplastic combination of CHOP-R

what cancers is it used for

Cyclophosphamide

Hydroxydaurnorubicin

Oncovin

Prednisone

Rituximab

CHOP-R is used for the treatment of non-hodgkin's lymphoma

what is the antineoplastic combination CAV

and what cancers is it used for

cyclophosphamide

adriamycin

vincristine

CAV is used in the treatment of lung cancer

bladder toxicity (hemorrhagic cystitis) - due to accumulation of acrolein

myelosuppresion (dose limiting with cyclophosphamide)

secondary malignancy

high risk emesis

pulmonary toxicity

nitrosoureas are what type of antineoplastic

what are the two main nitrosoureas

what are their MOA

nitrosoureas are DNA alkylating drugs

carmustine

lomustine

these drugs activate spontaneously to an intermediate that cross-links DNA causing DNA damage and activation of the repair machinery resulting in apoptosis

what are the common cancers treated by carmustine

and what are its side effects

CNS tumors (using the wafer administration route)

lymphoma

pulmonary toxicity

secondary malignancy

delayed myelosuppresion

high risk emesis

various CNS effects

list the main platinum compounds used for chemotherapy

what group of antineplastic are they a part of

platinum compounds are DNA alkylating drugs

cisplatin carboplatin

Testicular cancer (+ bleomycin +etoposide)

colon cancer (FOLFOX)

renal toxicity

severe N/V

ototoxicity

peripheral neuropathy

myelosuppression

anthracyclines:

doxorubicin

daunorubicin

mitotic inhibitors:

vinca alkaloids: vincristine; vinblastine

taxanes: paclitaxel; docetaxel

hydroxydaunorubicin

adiamycin

the natural products/anthracyclines

MOAs:

DNA intercalation (insertion of planar molecules between DNA base pairs, altering the DNA structure, activating the repair machinery - resulting in apoptosis)

inhibits DNA topoisomerase II (maintains topological DNA structure, inhibiting the religation of DNA)

Generates free radicals (damages DNA, protein, and cell membranes

daunorubicin:

AML

ALL

doxorubicin:

Breast Cancer

non-hodgkin's (CHOP-R)

hodgkin's lymphoma

Lung cancer (CAV - adriamycin)

CMF: cyclophosphamide, methotrexate, 5-UF

doxorubicin (natural anthracycline

paclitaxel (a taxane, (natural mitotic inhibitor)

tamoxifen (hormonal modulator, for early stage and metastatic ER(+))

cardiotoxicity (caused by the free radical generation)

vesicant tissue damage

myelosuppression

mucosal ulcers

alopecia

which antineoplastic drug has the adverse effect of vesicant tissue damage, a blistering and ulcerating condition that is [  ] dependent and may not show up for months

how can this effect be prevented

doxorubicin and daunorubinc can cause vesicant tissue damage

this can be treated with dexrazoxame, which also helps with the cardiotoxixity effect of these drugs as well

Vinca alkaloids:

vincristine

vinblastine

vincristine:

non-hodgkin's lymphoma (CHOP-R) (oncovin)

lung cancer (CAV)

vinblastine:

hodgkin's

peripheral neurotoxicity

extravasation can lead to injections site rxn

hyperuricemia

vinblastine has the additional adverse effect of: myelosuppression

vinca alkaloids:

vincristine

vinblastine

taxanes:

paclitaxel

decetaxel

paclitaxel is a taxane, which is part of the natural mitotic inhibitors

inhibits microtubule disassembly causing conitnual microtubule polymerization leading to apoptosis

breast cancer

kaposi's sarcoma

paclitaxel and docetaxel:

myelosuppression

alopecia

peripheral neuropathy

hypersensitivity rxns

cetuximab

rituximab

bevacizumab

trastuzumab

gemtuzumab ozogamicin

for monoclonal antibodies the letters "O, U, Xi" befor the "mab" indicates what possible species

"Tu, Vi, C or Ci" indicate what different types of proteins the drug is directed against

O: mouse

U: human

Xi: chimeric

Tu: tumor (directed toward receptor)

Vi: virus

C or Ci: circulation (directed toward ligand)

think tumor (Tu) and chimeric (Xi)

epidermal growth factor receptor - expressed in many cells but overexpressed in colon cancer, and overexpression if EGFR promotes uncontrolled cell growth and therefore cetuximab inhibits uncontrolled cell growth

colon cancer

squamous cell cancer

monoclonal antibody: think Tu (tumor receptor) and Xi (chimeric)

the exact MOA is unknown but it is thought to inhibit B-cell proliferation and survival via the target recptor of CD20 (typically found on non-hodgkin's lymphoma and normal B-cells)

rituximab: monoclonal antibody antineoplast agent

non-hodgkin's lymphoma (CHOP-R)

CLL (a type of leukemia that is more common in adults, but less progressive than ALL)

imantinib (Gleevec)

erlotinib (Tarceva)

imatinib (antineoplastic tyrosine kinase inhibitor):

inhibits the activity of a unique kinase enzyme that is expressed in CML (chronic myelogenous leukemia) cells that results from translocation of the specific genes responsible for the enzyme (and why it is not normally expressed in normal cells); specifically inhibits the bcr-abl fusion protein

CML (chronic myelogenous leukemia)

GI stromal tumors containing c-kit mutation

tamoxifen

aromatase inhibitors: anostrozole

antiandrogens: flutamide, bicalutamide

what type of drug is tamoxifen

what is the MOA

tamoxifen is an antineoplastic hormonal modulator agent

competitively inhibits estrogen binding to the estrogen receptor (because estrogen promotes the growth of breast cancer cells)

tamoxifen is a hormonal modulator

early stage and metastatic ER(+) breast cancer

anastrozole: an aromatase inhibitor which is a type of hormonal modulator antineoplast agent

postmenopausal, ER+ breast cancer

postmenopausal, ER+ breast cancer - tamoxifen resistant

flutamide and bicalutamide: antiandrogen hormonal modulators

bind to androgen receptors and inhibit effects of androgen, blocking the synthesis of androgen-targeted genes

flutamide: antiandrogen hormonal modulator

prostate cancer