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Flashcards in Oncology Drugs Deck (25)
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Methotrexate

Folic acid analog that inhibits dihydrofolate reductase - decreases dTMP which leads to decreased DNA and decreased protein synthesis.

Use in cancers (leukemias, lymphomas, choriocarcinomas, and sarcomas).

Use in non-neoplastic settings: abortion, ectopic pregnancy, RA, psoriasis, IBD.

Toxicity: myelosuppression (reversible by leucovorin). Macrovascular fatty change in the liver. Mucositus. Teratogenic (makes sense, it is an abortificant!)

How to remember: Luke covers (leucovorin) for and rescues Me from the TREX. Afterwards we eat foie gras (fatty liver) and red meat on the bone (myelosuppression).

1

5-fluorouracil

Pyrimidine analog bioactivated to 5F-dUMP, which covalently complexes folic acid. This complex inhibits thymidylate synthase --> dTMP --> decreased DNA and protein synthesis.

Used for colon caner, pancreatic cancer, basal cell carcinoma.

Toxicity: myelosuppression, NOT reversible with leucovorin. Overdose: rescue with uridine. Photosensitivity.

How to remember:
Fluorescent light--> photosensitivity --> stay in your basement (basal cell carcinoma). You also use fluorescent light to look at your colon during a colonoscopy.
Myelosuppression from drug tox man.
Uridine --> remember what I worked out with Natania earlier, 5-FU is turned into dUMP with a fluorine and competitively inhibits thymidylate synthase, so increasing the amount of uridine available will help...

2

Cytarabine / arabinofuranosyl cytidine

Pyrimidine analog --> inhibition of DNA polymerase.

Use for: leukemias, lymphomas

Toxicity: leukopenia, thrombocytopenia, megaloblastic anemia

Remember: CYTarabine causes panCYTopenia.
At Tara, Scarlet's father had a limp.

3

Azathioprine

Purine (thiol) analogs - decrease de novo purine synthesis. Activated by HGPRT (which is associated with Lesch-Nayan syndrome)! Inhibits purine synthesis thru feedback inhibition of enzymes involved in de novo purine synthesis.

Clinical use: preventing organ rejection, RA, SLE (azathioprine). Leukemia, IBD (6-MP, 6-TG).

Toxicity: Bone marrow, GI, liver. Azathioprine and 6-MP are metabolised by xanthine oxidase; thus both have increased toxicity with allopurinol, which inhibits their metabolism.

How to remember: 6- chemo tox man and myelosuppression.

The prince with the rheumatic thigh (azathioprine) prayed to allah (allopurinol) that his organs would not be rejected (organ rejection) before falling asleep (SLE/ lupus) with his crone wife (Crohns).

4

6-mercaptopurine

Purine (thiol) analogs - decrease de novo purine synthesis. Activated by HGPRT (which is associated with Lesch-Nayan syndrome)! Inhibits purine synthesis thru feedback inhibition of enzymes involved in de novo purine synthesis.

Clinical use: preventing organ rejection, RA, SLE (azathioprine). Leukemia, IBD (6-MP, 6-TG).

Toxicity: Bone marrow, GI, liver. Azathioprine and 6-MP are metabolised by xanthine oxidase; thus both have increased toxicity with allopurinol, which inhibits their metabolism.

How to remember: 6- chemo tox man and myelosuppression.

For 6-MP: The pure captain named luke got an ulcer (ulcerative colitis) after praying to allah (allopurinol).
For azathioprine:
The prince with the rheumatic thigh (azathioprine) prayed to allah (allopurinol) that his organs would not be rejected (organ rejection) before falling asleep (SLE/ lupus) with his crone wife (Crohns).

5

Dactinomycin / actinomycin D

Intercalates with DNA

Use for Wilms tumor, Ewing sarcoma, rhabdomyosarcoma, use for childhood tuomors.

Toxicity: myelosuppression.

Remember: in DNA. (actinomycIN D). Or DactinomycIN.
Children act out.
Wilbur tamed the Rabid (rhabdomyosarcoma) Ewes (Ewing sarcoma) who were acting miserably.

6

Doxorubicin / adriamycin / daunorubicin

Generates free radicals.
Mechanism: Intercalates in DNA -- breaks in DNA -- decreased replication.
1. Intercalates between base pairs.
2. Produces oxygen radicals.
3. Disrupts fluid / ion transports.

Clinical use: solid tumors, leukemias, lymphomas.

Toxicity: cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia. Toxic to tissues following extravasation.
Dexrazoxane (iron chelating agent) is used to prevent cardiotoxicity.

How to remember:
1. Dox and Dex.
2. Chemo tox man - D at the heart
3. Note- inappropriate. Prostitutes (er, doxies) a. get in between wives and husbands (intercalate), b. give birth to radicals, c. Disrupt transportation of fluids by stealing alcohol. They target solid relationships and lucky limpers. They are toxic to the heart, bones, and men's hair (alopecia).

7

Bleomycin

Induces free radical formation - binds DNA, generates free radicals -- DNA damage.

Testicular cancer, Hodgkin lymphoma

Pulmonary fibrosis, skin changes, mucositis. Minimal myelosuppression.

Remember: free radicals (MOA) and hos (Hodgkins lymphoma) give blow jobs (testicular cancer).
Pumonary toxicity from chemo tox man.

8

Cyclophosphamide

Covalently x-links (interstrand) DNA at guanine N-7. Require bioactivation by the liver.

Clinical use: solid tumors, leukemia, lymphomas, and some brain cancer.

Toxicity: myelosuppression, hemorrhagic cystitis (partially prevented with MESNA- thiol group of MESNA binds toxic metabolites).

S phase of DNA.

Mechanism of resistance: 1. Permeability, 2. DNA repair enzyme, 3. Reactions with glutathione.

How to remember: the dumb (brain tumor/ SOLID tumors) cyclops (cyclophosphamide) had bloody pee, looked like he was MESNAtruating (MESNA).
Chemo-tox man.

9

Ifosfamide

Covalently x-links (interstrand) DNA at guanine N-7. Require bioactivation by the liver.

Clinical use: solid tumors, leukemia, lymphomas, and some brain cancer.

Toxicity: myelosuppression, hemorrhagic cystitis (partially prevented with MESNA- thiol group of MESNA binds toxic metabolites).

S phase of DNA.

Mechanism of resistance: 1. Permeability, 2. DNA repair enzyme, 3. Reactions with glutathione.

How to remember: the dumb (brain tumor/ SOLID tumors) cyclops (cyclophosphamide) with one EYE (ifosfamide) had bloody pee, looked like he was MESNAtruating (MESNA).
Chemo-tox man.

10

Nitrosureas (carmustine, lomustine, semustine, streptozocin)

Require bioactivation.
Cross bbb --> CNS.

Treat brain tumors, including glioblastoma
Streptozocin also treats insulinomas

Toxicity: CNS toxicity, convulsions, dizziness, ataxia, bone marrow suppression, nephrotoxicity.

How to remember:
In keeping with the alkylating agents story.
The first sentence was the cyclops with one eye had bloody pee and looked like he was menstruating. (cyclophosphamide, ifosfamide).
For nitrosoures- KNIGHTS MUST use their BRAINS and STEP their TOES carefully.

11

Busulfan

Cross-links DNA, alkylating agent.

CML. Also used to ablate patient's bone marrow before bone marrow transplantation.

Side effects: severe myelosuppression (in almost all cases, pulm fibrosis, hyperpigmentation.

Remember:
The cyclops had bloody pee...
Knights must use their brains and step carefully...
From atop his CAMEL (CML), the TAN (hyperpigmentation) knight shoved the cyclops under the BUS and it BROKE ALL HIS BONES (severe myelosuppression) and SUFFOCATED (pulm fibrosis)

12

Vincristine / vinblastine

Vinca alkyloids that bind beta tubulin. Inhibit its polymerization into micritubules, thereby preventing mitotic spindle formation and LEAD TO M PHASE ARREST.

Clinical use: solid tumors, leukemias, and lymphomas.

Toxicity: vincristine- neurotoxicity, areflexia, peripheral neuritis, paralytic ileus.
Vinblastine- blasts bone, marrow suppression.

Remember: Christina has peripheral neuropathy.
Chemo tox man applies to vincristine not vinblastine

13

Paclitaxel and other taxels

Hyperstabilize polymerized microtubules in the m phase so that the mitotic spindle cannot bak down (anaphase cannot occur)

Also used to coat coronary artery stents to prevent restenosis.

Treat: ovarian and breast carcinoma

Side effects: myelosuppression, alopecia, hypersensitivity.

Remember that paclitaxel stabilizes microtubules, vinblastin BLASTS microtubules and destabilizes them.
Remember: BOTAX HAM - breast, ovary, taxols. Hypersensitivity, alopecia, myelisuppression.

14

Cisplatin and carboplatin

Alkylating - like, not a real alkylating agent.
Cross-links DNA.

Use for testicular, bladder, ovary, and lung carcinoma.

Toxicity: nephrotoxicity, and acoustic nerve damage. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis.

Remember: Cp earrings for ototoxicity and chem tox man for nephrotoxicity. Ami fostine nephrotoxicity cisplatin - my friend was fostered as my nephew's cister (cisplatin).

15

Etoposide / teniposide

Etoposide inhibits topoisomerase ii and increases dna degradation
Topoisomerase ii induces double stranded breaks.

Late s-g2 cell cycle


Clinical use: solid tumors, particularly testicular and small cell lung cancer, leukemias, lymphomas, glioblastoma multiforme

Toxicity: myelosuppression, GI irritation, alopecia

Remember:
I - irina's top
II - eating and playing tennis can happen multiple times.

White (leukemias, lymphomas are white cell cancers) east side (etoposide) tennis (tenoposide) players try smoking (small cell lung cancer) and sex (testicular cancer).

16

Irinotecan, topotecan

Inhibits topoisomerase i and prevents dna unwinding and replication

Colon cancer (irinotecan) and ovarian and small cell lung cancers (topotecan)

Toxicity: severe myelosuppression and diarrhea.

Remember: one irina's top eats and plays tennis multiple times.
Irina colossimo loves tea cans- irinotecan colon cancer, lung and ovary topotecan.

17

Hydroxyurea

Inhibits ribonucleotide reductase (which reduces ribonucleotides to a, g, c, u and decreases DNA synthesis - s phase specific.

Use for melanoma, CML, sickle cell disease (increase HbF)…

Bone marrow suppression, GI upset.

Remember: ox --> oxygen --> sickle cell disease, something about gnomes on camels...


18

Prednisone, prednisolone

May trigger apoptosis, may even work on nondividing cells

Most commonly used glucocorticoid in cancer chemotherapy. Used in CLL, non-hodgkin lymphomas as part of combination chemotherapy regimen. Also used as immunosuppressants (eg autoimmune diseases).

Toxicity: cushing-like symptoms, wt gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis, vertigo.

Remember: it's freaking prednisone- you can remember this one on your own!

19

Tamoxifen, raloxifene

Selective estrogen receptor modulator (SERM) - receptor antagonist in breast and agonist in the bone. Block the binding of estrogen to ER+ cells.

Breast cancer treatment (tamoxifen only) and prevention. Raloxifene also useful to prevent osteoporosis and breast cancer.

Tamoxifen - partial agonist in endometrium, which increases the risk of endometrial cancer, hot flshes.

Raloxifene - no increase in endometrial carcinoma, it is an endometrial antagonist.

20

Trastuzumab

Myoclonal antibody against her-2 (c-erb2) - a tyrosine kinase receptor. Helps kill breast caner cells that overexpress her2, through inhibition of her2 initiated cellular signalling and antibody dependent cytotoxicit.

Her2 positive breast cancer and gastric cancer - tras2zumab

Remember:
Cardiotoxicity - remember chemo tox man.

Remember that tyrosine kinases are 2 subunits that come together.

21

Imatinib

Gleevec. Tyrosine kinase inhibitor of the bcr-abl philadelphia chromosome in cml and c-kit common in gi stromal tumors.

Cml, gi stromal tumors, brain tumors.

Toxicity: fluid retention.

Remember: put the Beaker (bcr) and the KIT (ckit) on the MAT.

22

Rituximab

Monoclonal antibody against CD20 which is found on most B cell neoplasms

Non-hodkin lymphoma, rheumatoid arthritis (with MTX), ITP

Increased risk of progressive multifocal leukoencephalopathy.

Remember: 20 (cd 20) year olds probably couldn't write a great novel, but they could WRITE (rit) a b (B cells) movie.

23

Vemurafenib

Small molecule inhibitor of forms of the b-raf kinase with the v600e mutation

Use for metastatic melanoma.

Remember: RAFting on the river means you're out in the sun and you'll get melanoma!

24

Bevacizumab

Monoclonal antibody against VEGF. Inhibits angiogenesis.

Use for solid tumors, colorectal cancer, renal cell carcinoma.

Side effects: hemorrhage and impaired wound healing.

Remember: bloody side effects, this is a vascular antibody. Veins have COLOR - colon, renal.

Song: bevacizumab is; MAB that's with it; binds VEGF and takes it out of the system!