Pharm- Anticancer

Front 1

Log Kill Hypothesis

Back 1

In cancers. with very high growth fraction (lots of division) a given dose will kill a constant fraction of the tumor cells in the body.

Front 2

Compertzian kinetics

Back 2

Use for solid tumors. As tumor gets larger and larger the growth fraction goes down meaning it slows down in active percent number of divisions. Percentage of cells killed depends on growth fraction.

Front 3

Combination Chemo principles

Back 3

Each acts individually on the cell. Interaction of the drugs produces optimum effect. Different major toxicities, optimum scheduling and doses.

Front 4

MOPP

Back 4

Mechlorethamine, Oncovin, Prednisone, Procarbazine. Combo therapy for Hodgkins. All worked individually but not great by itself. All worded on it differently as well.

Front 5

Adjuvant Chemo

Back 5

Surgery or radiation therapy. Different types of therapy used together. Chemo than surgery or vice versa or radiation.

Front 6

Alkylating agents and platinum analogs

Back 6

bis(chloroethyl)amines, alky sulfonate, nitrosoureas, ethylenimine are all classes.

Front 7

bis(chloroethyl)amines

Back 7

Alkylating agents. Mechlorethamine, melphalan, and chlorambucil. One chlorine leaves and a cyclic ammonium ion is formed which is very active then you get a carbonium ion as well. Interaction with a negative charge anywhere can occur but they bind to DNA bases in cancer. Specifically the guanine residue #7 nitrogen. Because of 2 chlorines can react with two DNA molecules getting cross-linking. Interferes with synthesis.

Front 8

Adverse effects of alkylating agents.

Back 8

Myelosuppression (lowering WBC count, there is delay after dosage in lowering of WBC count though), GI issues(mucosa subject to damage and emesis very likely. Anti-emetic therapy very important), reproductive effects, carcinogenicity.

Front 9

Mechlorethamine differences

Back 9

Strong vesicant (blistering of skin if exposed) so use i.v. Other is p.o.

Front 10

Cyclophosphamide and Ifosfamide(similar drug)

Back 10

bis(chloroethyl)amine alkylating agent. Has cyclic ring. Has to be hydroxylated in liver before it can act. Still has chloroethyl group though. Immunosupressant. Hemorrhagic cystitis is possible side effect so make them pee a lot to flush drug out. Use for hematologic and solid tumors.

Front 11

Nitrosoureas

Back 11

Iomustine, carmustine. Highly lipid soluble so is very useful in brain tumors. Cause bone marrow suppression but it's delayed.

Front 12

Streptozocin

Back 12

Nitrosoureas used for pancreatic cancer. Myelosuppression and renal toxicity.

Front 13

Busulfan

Back 13

just another alkylating agent.

Front 14

Procarbazine

Back 14

Nonclassical alkylating agent. Myelosuppression, neurotoxicity, disulfiram life effect with alcohol, increased BP after Tyramine. Use in Hodgkin's disease.

Front 15

Dacarbazine (DTIC)

Back 15

Nonclassical alkylating agent

Front 16

Cisplatin

Back 16

Platinum analog. Binds to DNA and inhibits DNA synthesis/function and proteins. Renal, bone, oto toxicities, Puking. Peripheral neuropathy. Electrolytes, allergies.

Front 17

Other platinum analongs

Back 17

Carboplatin, oxaliplatin

Front 18

Antimetabolites

Back 18

Chemicals that resemble endogenous compounds and interact in a way to inhibit action.

Front 19

Methotrexate

Back 19

Antimetabolite that resembles folic acid. A methyl and a amine group are different. Inhibits dyhydrofolatereductase which stops one carbon transfers by thymidylate synthase. Can give many ways but you can get liver, GI, and myelosuppression. Mucositis is common which is ulcers on mouth. Also use in rheumatoid or psoriasis

Front 20

Leucovorin or folinic acid

Back 20

Tetrahydrofolate with another group. Used in excessive doses of methotrexate.

Front 21

Pemetrexed

Back 21

New methotrexate. Inhibits thymidylate syntahse and DHFR. Folic acid and B12 supplements reduce toxicity.

Front 22

Purine and Pyrimidine Analos

Back 22

Prodrugs that resemble nucleosides and are activated to look like nucleotide. They then block synthesis.

Front 23

6-mercaptopurine

Back 23

Inhibits purine biosynthesis. Looks like hypoxanthine. Put into nucleic acids. Methylation polymorphism makes the drug act differently. Liver toxicity and immunosuppression. Important interaction with allopurinol.

Front 24

6-thioguanine

Back 24

Looks like a guanine. Methylation polymorphism in the population. Deaminated to 6-thioxanthine so it doesn't need xanthine oxidase and doesn't react with allopurinol.

Front 25

Fludarabine phosphate and Cladribine

Back 25

Both are purine analogs. FP has a phosphate that is removed before entrance into cell.

Front 26

5-Fluorouracil

Back 26

Uracil analog. Fluorine replacing hydrogen. FdUMP inhibits thymidylate synthase. Stops dUMP from going to dTMP. Same stuff but neurotoxicity in some cases.

Front 27

Cytarabine

Back 27

Cytosine analog. Hydroxyl group instead of a methyl in the ribose ring. Inhibits DNA chain elongation.

Front 28

Gemcitabine

Back 28

Pyrimidine analog. Inhibition RN reductase. One of the first drugs approved for pancreatic cancer.

Front 29

Dactinomycin (actinomycin D)

Back 29

Antitumor antibiotics that binds DNA by sandwiching itself inbetween pairs. Inhibits RNA synthesis. Get normal stuff but also alopecia and tissue damage if extravasated. Used for Wilm's tumor.

Front 30

Anthracycline (daunorubicin and doxorubicin)

Back 30

Antitumor antibodies. Intercalate into DNA. Inhibit toposiomerase II (same as gyrase). Free radical damge and membrane binding. Same as dactinomycin adverse effects plux cardiotoxicity. The cardio is the classic one.

Front 31

Cardiotoxicity of doxorubicin chronic form.

Back 31

Cardiomyopathy. Mainfested as HF. Related to cumulative dose. May occur during or months-years after Rx. Mechanism is thought to be related to free radical formation. Can get acute ECG or carditis presentation.

Front 32

Bleomycin

Back 32

Antitumor antibody. Binds to DNA and Iron?? and produces free radicals. This breaks the DNA strand. Pulmonary symptoms like cough and dyspnea, pulmonary infiltrate, increase risk with old age.

Front 33

Vinca Alkaloids (Vincrisinte and Vinblastine)

Back 33

Plant derived antitumor meds.Bind tubulin and inhibit polymerization. This leads to mitotic arrest. This causes apoptosis.

Front 34

Vinblastine/Vincristine side effect comparison.

Back 34

Blastine has less neurotoxicity and more bone marrow. Cristine has more neuro and less bone marrow.

Front 35

Taxanes (paclitaxel)

Back 35

Plant derived antitumor. Binds microtubles and inhibits depolymerization. Peripheral neuropathy and arrhythmmias possible.

Front 36

Epipodophyllotoxins (etoposide)

Back 36

Plant derived antitumor. Inhibits Topoisomerase II. Dna strand breaks. secondary leukemia possible.

Front 37

Camptothecins (topotecan and irinotecan)

Back 37

Plant derived antitumor. Inhibit topo I.

Front 38

Asparaginase

Back 38

Natural enzyme used in anticancer. Converts L-asparagine to aspartic acid and NH3. Asparagine is required by tumor cells and we lower the level. Decreases protein synthesis in tumor cells but also synthesis of human cells like clotting factors.

Front 39

Imitanib (Gleevec)

Back 39

Inhibits Bcr-Abl tyrosine kinase. Oral administration. Binds ATP binding site and doesn't allow for phosphorylation of tumor cells. Can have neutro and thrombocytopenis and maybe liver effects.

Front 40

Dasatinib and nilotinib.

Back 40

Also inhib Bcr-Abl kinases. Used for people resistant to Gleevec.

Front 41

Cetuximab and panitumab

Back 41

Monoclonal antibodies that bind to EGF receptor and inhibit downstream signaling. Can get acneiform rash and interstitial lung disease.

Front 42

Gefitinib and erlotinib

Back 42

Tyrosine kinase domain or EGF receptor inhibitor. Small enough to actually get in the cell. Same effects as cetux and panit. Rash is bright papular rash.

Front 43

Bevacizumab

Back 43

Binds vascular endothelial growth factor. Cuts off vascular tissue growth. Can get bleeding, GI perforation, wound healing problems, HTN, thromboembolic events.

Front 44

Sorafenib and sunitinib

Back 44

Multiple receptor tyrosine kinases including some VEGF receptors. Bleeding problems obviously.

Front 45

All-trans-retinoic acid (tretinoin) and arsenic trioxide

Back 45

Induce differentiation in acute promyelocytic leukemia.

Front 46

Bortezomib

Back 46

Inhibits proteosomes in the cell. Why would that help... i have no idea.

Front 47

Hydroxyurea

Back 47

Inhibits ribonucleotide reductase and decreases DNA synthesis. Used in CML.

Front 48

INF-a, interleukin-2, and other antibodies have antitumor effects.

Back 48

Just know that apparently.