Pharm Oncology Flashcards

1
Q

Describe the cell cycle. tumor suppressors modulate the G1 restriction point? What classes of drugs/drugs work during the S phase? G2 phase? M phase? G1/G0 phase?

A

MItosis occurs in which cell in split in two.
G0 is resting phase.
G1 is when the cellular content is duplicated (Rb, p53 modulate checkpoint before next step)
In S phase, DNA is duplicated
In G2, the DNA is checked again to make sure there were no mistakes
M phase again.

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2
Q

What is the mechanism of azathioprine (1), 6 mercaptopurine (2), and 6 thioguanine? How are they used clinically? Toxicity? How are they activated? How is 1 activated? What increases toxicity of 1 and 2?

A

Purine analogs which leads to decr. de novo purine synth

Activated by HGPRT

1 is metabolized into 6-MP

Preventing organ rejection
RA
IBD
SLE
Wean pts. off steroids
Treat steroid refractory chronic disease

Myelosuppresion
GI
LIver

1/2 metabolized by XO, so allopurinol and febuxostat incr. toxicity

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3
Q

What is the mechanism of Cladribine (2CDA)? Clinical use? Toxicity?

A

Purine analog that has multiple mechanisms (strand breaks, inhibition of DNAP)

Hairy Cell Leukemia

Myelosuppression
Nephrotoxicity
Neurotoxicity

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4
Q

What is the mechanism of cytarabine? Use? Toxicity?

A

Pyrimidine analog leading to inhibition of DNAP

Leukemias (AML), lymphomas

Leukopenia
thrombocytopenia
megaloblastic anemia

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5
Q

What is the mechanism of 5-flourouracil? Uses? Toxicity? Reversal?

A

Pyrimidine analog that Inhibits thymidylate synthase leading to decr. dTMP leading to decr. DNA

Colon cancer, pancreatic cancer, basal cell CA (topical)

Myelosuppresion (not reversible with leucovorin)

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6
Q

What is the mechanism of methotrexate? Use? Toxicity?

A

Folic aid analog that competitively inhibits DHFR leading to decr. dTMP and decr. DNA synth

Cancers: Leukemias (ALL), lymphomas, chorioCA, Sarcomas

Ectopic pregnancy
Medical abortion (with misoprostol)
RA
Psoriasis
IBD
Vasculitis

Myelosuppresion (reversible with leucovorin)
Hepatotoxicity
Mucositis
Pulm. fibrosis

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7
Q

What is the mechanism of bleomycin? Use? Toxicity?

A

Induces free radical formation lt breaks in DNA strands

Testicular cancer, Hodgkins lymphoma

Pulm. fibrosis, skin hyperpig, mucositis
Minimal myelosuppresion

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8
Q

What is the mechanism of dactinomycin? Use? Toxicity?

A

intercalates in DNA

Wilms tumor
EWING sarcoma
rhabdomyosarcoma
childhood tumors (children ACT out)

Myelosupprsion

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9
Q

What is the mechanism of doxorubicin and daunorubicin? Use? Toxicity? Prevention?

A

Generates free radicals
Intercalates in DNA lt breaks in DNA lt decr. replicaiton

Solid tumors, leukemias, lymphomas

Cardiotoxicity (dil cardiomyopathy)
myelosuppression
Alopecia

Dexrazoxane used to prevent CM

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10
Q

What is the mechanism of busulfan? Use? Toxicity?

A

cross links DNA

CML
ablate patients bone marrow prior to transplant

Severe myelosuppresion (in almost all cases)
pulm. fibrosis
hyperpigmentation

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11
Q

What is the mechanism of cyclophosphamide, ifofsamide? Use? Toxicity?

A

Cross link DNA at guanine N-7.
Bioactivation by liver

Solid tumors, leukemia, lymphomas

Myelosuppresion
Hemorrhagic cystitis

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12
Q

What is the mechanism of nitrosoureas (carmustine, lomustine, semustine, streptozocin)? Use? Toxicity?

A

Require bioactivation
Cross BBB
Cross link DNA

Brain tumors (including GBM)

CNS toxicity (convulsions, dizziness, ataxia)

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13
Q

What is the mechanism of paclitaxel (other taxols)? Use? Toxicity?

A

Hyperstabilizes microtubules in M phase so taht mitotic spindle cannot break down (anaphase cannot occur)
“It is taxing to stay polymerized”

Ovarian and breast CAs

Myelosuppresion
Alopecia
HSR

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14
Q

What is the mechanism of vincristine (1), vinblastine (2)? Use? Use of 1? 2? Toxicity 1? 2?

A

Vinca alkaloids that bind beta tubulin and inhibit its polymerization into microtubules lt preventing of mitotic spindle formation

Solid tumors, leuk, HL (2), NHL (1), lymphomas

1=neurotoxicity (areflexia, periph neuritis, paralytic ileus)
2=myelosuppression

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15
Q

What is the mechanism cisplatin/carboplatin? Clinical use? Toxicity?

A

Cross link DNA

Testicular, bladder, ovary, and lung CA

Nephrotoxicity, ototoxicity

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16
Q

What is the mechanism etoposide, teniposide? Clinical use? Toxicity?

A

Inhibits topoisomerase II lt incr. DNA degradation

Solid tumors (test and Small Cell lung cancer)
leuk and lymph

myelosuppresion, GI upset, alopecia

17
Q

What is the mechanism irinotecan (1), topotecan (2)? Clinical use 1? 2? Toxicity?

A

Inhibit topoisomerase I and prevent DNA unwinding and replication

Colon cancer-1
ovarian and small cell lung cancers-2

Severe myelosuppresion
Diarrhea

18
Q

What is the mechanism hydroxyurea? Clinical use? Toxicity?

A

Inhibits ribonucleotide reductase leading to decr. DNA synth

Melanoma, CML, Sickle cell disease (incr. HbF)

Severe myelosuppression
GI upset

19
Q

What is the mechanism prednisone, prednisolone? Clinical use? Toxicity?

A

Various; bind intracytoplasmic receptor; alter gene transcription

Most commonly used glucocorticoids in cancer chemo
CLL, NHL
Immunosuppressants (auto immune)

Cushing like symptoms: weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis

20
Q

What is the mechanism bevacizumab? Clinical use? Toxicity?

A

MAB against VEGF. Inhibits angiogenesis

Solid tumors (CRC, RCC)

Hemorrhage, blood clots, impaired wound healing

21
Q

What is the mechanism erlotinib? Clinical use? Toxicity?

A

EGFR tyrosine kinase inhibitor

Non-small cell CA

Rash

22
Q

What is the mechanism imatinib? Clinical use? Toxicity?

A

Tyrosine kinase inhibitor of BCR-ABL (CML; 9;22) and c-kit (GIST)

CML, GIST

Fluid retention

23
Q

What is the mechanism rituximab? Clinical use? Toxicity?

A

MAB against CD20, found in most b cell neoplasms

NHL, CLL, IBD, RA

Incr. risk of progressive multifocal leukoencephalopathy (JC virus)

24
Q

What is the mechanism tamoxifen (1), raloxifene (2)? Clinical use? Toxicity?

A

SERMs-receptor antag in breast and agonists in bone
Block binding of estrogen to ER + cells

1=Breast cancer treatment and prevention
2=prevent osteoporosis

1=partial agonist in endometrium, which incr. risk of endometrial cancer; hot flashes
2=no incr. in endometrial CA b/c it is an antag there

25
Q

What is the mechanism trastuzumab (herceptin)? Clinical use? Toxicity?

A

MAB against HER-2, and tyr kin receptor
Kills cancer cells that overexpress HER-2 through inhibition of HER-2 initiated cellular signaling and antibody dependent cytotoxicity.

HER-2 + breast cancer and gastric cancer

Cardiotoxicity

tras2zumab
“heart”ceptin

26
Q

What is the mechanism vemurafenib? Clinical use?

A

small molecule inhibitor of BRAF oncogene + melanoma

Metastatic melanoma

27
Q

Describe the chemo tox man? Where are things located and what do they mean?

A

Ears made up of C’s (cisplatin and carboplatin lead to acoustic nerve damage)

Arms and legs are both V’s (Vincristine leads to periph. neuro)

Lungs made of B’s (bleomycin and busulfan both lead to pulm. fibrosis)

Heart made up of a D with a T splitting it into 4 chambers (Doxorubicin and trastuzumab lead to cardiotoxicity)

Kidneys made up of C’s (Cisplatin/carboplatin are nephrotoxic)

Bladder made up of upside down C and urethra a Y(CYclophoshamide=hemorrhagic CYstitis)

5,6 at top of femur leading down to an M at bottom of femur (5-FU, 6-MP, and methotrexate all lead to myelosuppression)