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Exam 1 Pharm 2
N/A
84
Pharmacology
Professional
02/01/2012

Additional Pharmacology Flashcards

 


 

Cards

Term

Rubicins:  Daunorubicin, Doxorubicin, Epirubicin, Idarubicin

 

1.  Class

2.  Structrual subclass

3.  MOA

Definition

1.  Antitumor antibiotic

 

2.  Anthracycline

 

3.  A)  Inhibit topo II; B) high-affinity binding to DNA through intercalation; C) Binding to cell membranes, althering fluidity and transport; D) Generation of semiquinone free radicals and oxygen free radicals that damage DNA

Term

"Relins":  Buserelin, nafarelin, histrelin, deslorelin + Leuprolide

 

1.  Class

2.  Structural subclass

3.  MOA

Definition

1.  Hormonal agents

 

2.  GnRH receptor agonists

 

3.  Overstimulate GnRH receptor, stimulating negative feedback, preventing release of gonadal estrogens and androgens

Term

Relix drugs:  Cetrorelix, ganirelix, abarelix, degarelix

 

1.  Class

2.  Structural subclass

3.  MOA

Definition

1.  Hormonal agent

 

2.  GnRH receptor antagonist

 

3.  Directly blocks GnRH receptor-mediated release of gonadal estrogens and androgens

Term
What do you look for in selective toxicity chemo?
Definition

Somethign crucial to functioning of that organism/cell, but missing frmo human body and use a drug to disable it

 

*Problem is that cancer cells are human cells which makes finding something unique difficult

Term
Define Cancer:
Definition
Cell growing out of control that has proliferation gene mutations allowing unregulated growth
Term

1.  Define malignant

 

2.  How are they named

Definition

1.  Tumor that can result in death and metastasize to other organs

 

2.  Origin:  carcinoma = epithelial and sarcoma = connective tissue

Term
Define benign
Definition

1.  Tumor that usually does not cause necrosis of neighboring tissue, metastasize to other organs or result in death (although some may mutate to become malignant)

 

*usually end in -oma (except melanoma and glioma-doesn't metastasize but can cause death)

Term
Define Log-kill hypothesis
Definition

Most chemo agents kill 99.99% of cacner cells, but the remaining 0.01% may cause recurrence (tumor regrowth or metastasis).  

 

Toxic effects of chemo mandate lag between treatment so cancer can regenerate.

Term
How do you minimize growth periods to avoid log-kill hypothesis from occuring?
Definition

1.  Debulking

 

2.  Combo therapy using radiation and other drugs for shorter time b/t tx

Term

1.  Define Cell Cycle Specific Drugs

 

2.  Define Cell Cycle Nonspecific Drugs

Definition

1.  Only target a particular component of cell cycle (mainly G1)

 

2.  Cell-cycle non-specific drugs can kill in both G0 and cycling cells, although cycling cells more sensitive

Term
Classes of CCS Chemo Drugs (5)
Definition

1.  Antimetabolites

2.  Antitumor Antibodies

3.  Epipodophyllotoxins

4.  Taxanes

5.  Vinca alkaloids

Term
Classes of CCNS Chemo Drugs (5)
Definition

1.  Alkylating agents

2.  Anthracyclines

3.  Antitumor antibodies

4.  Camptothecins

5.  Platinum analogs

Term
2 Methods by which alkylating agents cause cell death
Definition

1.  Alkylation of DNA (N7 of G, O6 of G, N1 and 3 of A, N3 of C) blocking replication machinary

 

2.  Alkylation of cellular proteins by reacting with nucleophiles such as sulfhydrul, amino, hydroxyl, carboxyl, and phosphate groups

 

*most are bifunctinoal 

Term

Bis(chloro-ethyl)amines

 

1.  Class of chemo

2.  Members of group (5)

3.  MOA

Definition

1.  Alkylating agents

 

2.  Cyclophosphamide, mechlorethamine (nitrogen mustard), melphalan, chlorambucil, benamustine 

 

3.  Chloro-ethyl group alkylates N7 of 2 adjacent purines (intrastrand link)

Term

Nitrosoureas

 

1.  Chemo group

 

2.  Nitrosoureas (4)

 

3.  MOA

 

4.  Special property for difficult to reach tumors

Definition

1.  Alkylating agents

2.  Carmustine (BCNU); lomustine, semustien, streptozocin

 

3.  Alkylate G at N7 primarily, but toxicity is from minor G O6 alkylation causing CG crosslinks inter or intrastrand

 

4.  Lipid soluble so can pass through BBB to tx brain tumors

Term

Ethyleneimines or Aziridines

 

1.  Class

 

2.  Members of group (3)

 

 

Definition

1.  Alkylating agents

 

2.  Thiotepa (ovarian cancer), triethylenemelamine, altretamine

Term

Platinum Analogs

 

1.  Class

 

2.  Members

 

3.  MOA

Definition

1.  Alkylating agents

 

2.  Cisplatin; Carboplatin; Oxaliplatin

 

3.  Form inter and intrastrand DNA cross-links inhibiting DNA synthesis and funciton

Term
Oxaliplatin:  place in therapy
Definition
Cancers resistant to cisplatin and carboplatin 
Term

Imidazotetrazine derivatives

 

1.  Class

 

2.  Members (1)

 

3.  MOA

Definition

1.  Alkylating agents

 

2.  Temozolomide

 

3.  Rapid nonenzymatic conversion at physiologic pH to reactive MTIC which alkylates DNA at O6 and N7 positions of Guanine...used for brain cancers

Term

Methylhydrazine Derivative

 

1.  Class

 

2.  Member (1)

 

3.  MOA

Definition

1.  Alkylating agents

 

2.  Procarbazine

 

3.  Not clear, but may inhibit protein, RNA, and DNA synthesis

Term

Imidazole Carboxamide

 

1.  Class

2.  Drug (1)

3.  MOA

Definition

1.  Alkylating agent

 

2. Dacarbazine

 

3.  Hypothesized to be:  A) Inhibition of DNA synthesis by acting as purine analog; B) action as alkylating agent; C) interaction with sulfhydryl groups

Term

Antimetabolites:

 

1.  Direct MOA

 

2.  Indirect MOA

Definition

1.  Inhibit nucleotide and nucleic acid synthesis by:  inhibiting enzymes involved in DNA replication and/or nucleotide synthesis pathways and/or mimicing nucleotides for incorporation into nucleic acids

 

2.  Inhibit tumor growth through inhibition of DNA synthesis; inhibit cell maintenance through inhibition of protein synthesis; stimulate apoptosis

Term

DHFR and Thymidylate Synthases (TS)

 

1.  What does DHFR do?

2.  What it it's product an essential for in the cell?

3.  Role of TS

4.  How do DHFR and TS inhibitors affect cancer cells?

Definition

1.  Reduces dihydrofolate to tetrahydrofolate (active folic acid) 

2.  Essential cofactor for de novo thymidine synthesis to make pruine nucleoties, and a portion of the serine/methionine cycle

3.  Transfers methyl from methylene THF onto dUMP to make dTMP

4.  Stop replication directly (TS) or indirectly (DHFR)

Term
TS and DHFR Inhibitors role with one another
Definition
Both indirectly inhibit the other because of their interrelated nature within the cycle causing thymine-less cell death
Term

Methotrexate

 

1.  Class

2.  Subclass

3.  MOA

Definition

1.  Antimetabolite

 

2.  Folic acid antagonist

 

3.  Binds active catalytic site of DHFR competitively (DHF is normal substrate) inhibiting synthesis of THF and stopping DNA, RNA, and protein synthesis

Term

Pemetrexed and Ralititrexed

 

1.  Class

2. MOA

Definition

1.  Antimetabolite

 

2.  MAIN ACTION: Inhibition of thymidylate synthase (TS) the methyltransferase making dTMP from dUMP

 

Also target DHFR

Term

Pyrimidine Antagonists

 

1.  Drugs (4)

 

Definition

1.  5-FU

Capecitabine

Cytarabine

Gemcitabine

Term

5-FU  and Metabolite

 

1.  Drugs (2)

 

 

Definition

1.  5-FU and Capecitabine

 

 

Term
5-FU Metabolites (3) and MOA
Definition

1.  Deoxyribosyl metabolite (FdUMP):  covalent binding and inhibition of Thymidylate synthase and thymine-less cell death

 

2.  Deoxyribosyl metabolite (FdUTP):  Inhibits DNA synthesis by incorporating into DNA and inhibiting DNA elongation

 

3.  Ribosyl metaabolite (FUTP):  Incorporates into RNA to interefere with RNA sythesis and mRNA translation thus inhibiting protein sythesis 

Term

Capecitabine

 

1.  What is it?

 

2.  What activates it and why is that good?

Definition

1.  Prodrug metabolized to 5-FU

 

2.  Thymidine phosphorylase which has significantly higher expression in solid tumors than normal cells leading to selective toxicity and reduced myelosuppression, mucositis, N/V

Term

Cytarabine

 

1.  Class

2.  Subclass

3.  MOA

Definition

1.  Antimetabolite

 

2.  Pyrimidine analog

 

3.  Inhibits DNA pol alpha and beta (like the purine antagonists fludarabine and cladribine)

Term

Gemcitabine

 

1.  Class

2.  Subclass

3.  MOA

Definition

1.  Antimetabolite

 

2.  Pyrimidine/deoxycytidine analog

 

3.  Mimics cytidine and is incorporated into DNA preventing elongation; Inhibits ribonucleotide recductase preventing production of dNTPs for DNA synthesis

Term

Purine Antagonists

 

1.  Class

2.  Subclass

3.  Drugs (2)

4.  MOA

Definition

1.  Antimetabolite

2.  6-thiopurines

3.  6-mercaptopurine (6-MP)

6-thioguanine (6-TG)

 

4.  Inhibit several enzymes in purine de novo biosynthetic pathway decreasing DNA and RNA synthesis by way of reducing avaible functional purines 

Term

Fludarabine and Cladribine

 

1.  Class 

2.  Subclass

3.  MOA

Definition

1.  Antimetabolite

 

2.  Purine antagonist

 

3.  Inhibit DNA polymerase alpha and beta (like pyrimidine antagonist cytarabine)

Term

Vinblastine and Vincristine:

 

1.  Class

2.  Subclass

3.  MOA

Definition

1.  Plant alkaloid

2.  Vinca (periwinkle) alkaloid

3.  Inhibits tubulin polymerization, halting cell cycle and leading to death

 

*SAme MOA but different clinical spectrum and toxicity profiles

Term

Vinorelbine

 

1.  Its claim to fame?

Definition
1.  Synthetic version of vinca alkaloids
Term

Epopodophyllotoxins

 

1.  Class

2.  Drugs (2) and source

3.  MOA

Definition

1.  Plant alkaloids

2.  Etoposide and Teniposide; mayapple root extract derivative of podophyllotoxin

 

3.  Inhibits topoisomerase II, causing DNA strand breakage leading to cell death

Term

Camptothecins

 

1.  Class

2.  Drugs (2) and source

3.  MOA

Definition

1.  Plant alkaloids

2.  Topotecan and irinotecan; fromt eh camptotheca tree

 

3.  Inhibit topoisomerase I, preventing cutting and religating of ssDNA leading to cell death

Term

Taxanes

 

1.  Class

2.  Drugs (2) and source

3.  MOA

Definition

1.  Plant alkaloids

2.  Paclitaxel and docetaxel; Pacific and European yew

*docetaxel is semisynthetic

 

3.  Enhances abnormal microtubule assembly without presence of regulatory proteins and GTP

Term

Antitumor antibiotics

 

1.  Classes (5)

2.  All derived from what?

Definition

1.  Anthracyclines, antracenes,dactinomycin, bleomycin, and mitomycin

 

2.  Soil microbe Streptomyces

Term

Anthracyclines

 

1.  Class

2.  Drugs (4)

3.  MOA

Definition

1.  Antitumor antibiotics

2.  Doxorubicin, daunorubicin, idarubicin, epirubicin

3.  A)  Inhibit topoisomerase II

B)  Intercalate DNA in major groove blocking replication machinery

C)Binding to cell membranes, altering fluidity and transport

D)  Generation of semiquinone radical through iron-dependent, enzyme-mediated reductive process (can also be caused by estrogen)...cardiotoxicity

Term

Anthracene

 

1.  Class

2.  Drug (1)

3.  MOA

Definition

1.  Antitumor antibiotics

2.  Mitoxantrone

3.  Resemble anthracyclines, bind to DNA to break strands inhibiting DNA and RNA synthesis

Term

Dactinomycin

 

1.  Class

2.  MOA

Definition

1.  Antitumor antibiotic

2.  Intercalating agent b/t adjacent G and C blocking replication machinery

Term

Mitomycin

 

1.  Class

2.  MOA

Definition

1.  Antitumor antibiotic

 

2.  Alkylating agent that cross-links DNA

Term

Bleomycin

 

1.  Class

2.  MOA

Definition

1.  Antitumor antibody

 

2.  Small peptide with DNA binding domain at one end and Fe binding domain at the other

 

Binds DNA and Fe end produces hydroxyl radicals ensuring more DNA damage

Term

Extrogen receptor antagonists

 

1.  Drugs (2)

 

2.  General mechanism of action

Definition

1.  Tamoxifen and raloxifene

 

2.  Inhibit estrogen receptor in ER + tumors

Term

Tamoxifen

 

1.  Class

2.  Subclass

3.  MOA

4.  Tissue response:  Breast, bone, uterus

Definition

1.  Hormonal agent

2.  Estrogen-receptor partial agonist

3.  With only partial activation of receptor, overall reduction in activation of receptor

4.  Breast:  Tx breast tumors and prevent recorrence or 2nd primary tumor

Bone:  MAY tx and prevent osteoporosis

Uterus:  Inc risk for 2nd primary uterine cancer

Term
Define 2nd primary tumor
Definition
Another original tumor as opposed to regrowth from cells left behind in the original tissue or metastasis in another tissue
Term

Raloxifene

 

1.  Class

2.  Subclass

3.  Response in Breast, Bone, Uterus

Definition

1.  Hormonal agent

 

2.  Estrogen-receptor partial agonist

 

3.  Breast:  tx tumors and prevents recurrence or 2nd primary tumor

Bone:  tx and prevents osteoporosis (remember that tamoxifen is a MAY here)

Uterus:  NO inc risk of 2nd primary uterine cancer

Term

Gonadotropin-releasing hormone agonists and antagonists

 

1.  MOA

2.  Antagonists (4)

3.  Agonists (5)

Definition

1.  bind to GnRH receptors and prevent gonadal release of estrogens and androgens

 

2.  "relix" drugs:  cetrorelix, ganirelix, abarelix, degarelix

 

3.  Leprilde and the "Relins" (good band name btw):  buserelin, nafarelin, histrelin, deslorelin

*Initially inc gonadal hormone release but then negative feedback

Term

Aromatase inhibitors 

 

1.  Class

2.  Drugs (4)

3.  MOA

Definition

1.  Hormonal agents

2.  Aminoglutethimide

Anastrozole

Letrozole

Exemestane

3.  Inhibit steroid hormone synthesis

Term

Aminoglutethimide

 

1.  Class

2.  Subclass

3.  MOA

Definition

1.  Hormonal agent

2.  Nonsteroidal corticosteroid synthesis inhibitor

3.  Inhibits conversion of cholesterol to pregnenolone; also inhibits estrone and estradiol synthesis which is loacalized to breast and uterus

Term
Reversible aromatase inhibitors (2)
Definition
Anastrazole and letrozole
Term
Irreversible aromatase inhibitors
Definition
Exemestane
Term

Imatinib (Gleevec)

 

1.  Class

2.  MOA

Definition

1.  Misc

 

2.  Non-competitive Bcr-Abl receptor antagonist

Bcr-Abl is an oncoprotein

Imatinib inactivates the tyr-kinase domain of the receptor preventing substrate phosphorylation

Term

Dasatinib (Sprycel)

 

1.  Class

2.  MOA

Definition

1.  Misc

 

2.  Nonselective Tyr-kinase receptor antagonist

Term

Epidermal Growth Factor Receptor (EGFR) Inhibtors

 

1.  Drugs (3)

2.  MOA

Definition

1.  Cetuximab (Erbitux), gefitinib (Iressa), erlotinib (Tarceva)

 

2.  EGFR overexpressed in many tumors so blocking these receptors prevents growth

 

*Different drugs act on either EGFR 1 or 2 so choice is dictated by tumor

Term

Vacualr endothelial growth factor receptor (VEGF) inhibitors

 

1.  Drug (1)

 

2.  MOA

Definition

1.  Bevacizumab (Avastin)

 

2.  VEGF moderates blood supply so blocking this cuts off blood supply to tumor

Term

Asparaginase

 

1.  Class

 

2.  Subclass

 

3.  MOA

Definition

1.  Misc

2.  L-asparagine amidohydrolase of bacterial origin

 

3. Breaks down L-asparagine; tumor cells lack asparagine synthetase so it must import exogenous L-asparagine which the Asparaginase removes

Term

Hydroxyurea

 

1.  Class

2.  Subclass

3.  MOA

Definition

1.  Misc

2.  Urea analog

3.  Inhibits DNA synthesis by inhibiting ribonucleotide reductase (like gemcitabine), preventing production of dNTPs for DNA synthesis

Term

Retinoic Acid Derivatives

 

1.  Drug (1)

2. MOA

Definition

1.  Tretinoin = All trans-retinoic acid

 

2.  Induces terminal differentiation, preventing proliferation

Term

Arsenic trioxide

 

1.  Class

2.  MOA

Definition

1.  Misc

2.  Induces terminal differentiation, preventing proliferation

Term
What must occur before cancer treatment is allowed to begin?
Definition
Cancer is typed and staged by a pathologist
Term

1.  Tumors are ____ cell masses

 

2.  Stages of tumor growth (6)

Definition

1.  Heterogenous

 

2.  Initiation

Promotion

Conversion or transformation

Progression

Local invasion

Metastasis

Term

1.  Different characteristics of different tumor cells often make combination therapy necessary and can result in ____ and/or ____

 

2.  What 2 things accound for the high failure rate of chemo in advanced cancers?

Definition

1.  Lethal tox of chem and/or MDR

 

2.  A) Heterogenous nature of tumors

B)  Perpetual accumulation

Term

Adjuvant Cancer Therapy

 

1.  Function

 

2.  2 types she listed

Definition

1.  Systemic tx to prevent micrometastases after local Tx 

 

2.  Surgery and radiation

Term

Palliative cancer tx

 

1.  2 goals listed

Definition

1.  Shrinking tumors causing blockage or constriction

 

Relief of bone pain

Term
Define role staging and diagnostic cancer surgery (2)
Definition

1.  Provides staging 

 

2.  Determines how much cancer is there and how far it has spread

Term
Define role of preventative cancer surgery (2)
Definition

1.  Precancerous lesions:  moles or polyps

 

2.  Removal of organs with things like BRCA mutation or colostomy with MMR mutation

Term
Define role of debulking surgery (3)
Definition

1.  Debulks tumors that cannot be completely removed aiding radiation and chemo

 

2.  Prolongs life

 

3.  Provides relief from bloackage, constriction, and pain

Term
Define role of palliative surgery (1)
Definition
Improving pt comfort and/or prolonging life 
Term
3 majors goals of radiation therapy
Definition

1.  To cure or shrink early stage cancer

 

2.  To prevent metastases

 

3.  To tx symptoms for advanced cancer

Term

Ionizing radiation

 

1.  MOA

 

2.  2 major types and their particles (or waves if you really want to get physics-y)

Definition

1.  Forms ions by dislodging electrons as it passes through cell

 

2.  Photons:  gamma and X-rays (most common)

Particles:  electrons, protons, neutrons, alpha and beta particles

 

*more energy = better penetration, but also more collateral damage

Term

High-Energy Photon Radiation

 

1.  Source

Definition

1.  Cobalt, cesium, or a linear accelerator

 

*most common type used today

Term

Electron beam radiation

 

1.  Source

 

2.  What type of tumors is it used for?

Definition

1.  Linear accelerator

 

2.  Less penetration so used for surface tumors

Term

Proton radiation therapy

 

1.  Advantage

 

 

Definition

1.  Dumps all its energy at end of path in cancer cell so less damage to surrounding tissue

 

*still newer and needs to be studied in more cancer types

Term

Neutron radiotherapy

 

1.  Cancers used for 

 

2.  When used?

 

3.  Why bad?

Definition

1.  Head, neck, prostate

 

2.  Sometimes helpful when other forms of radiation don't work

 

3.  Severe long-term side effects so use is limited

Term

External Beam Radiation

 

1.  MOA

Definition

1.  Most widely used today

 

Linear accelerator focuses beam on tumor, but it also hits normal tissue

 

Allows large body area to be tx

Term

Internal Radiation Therapy

 

1.  AKA

 

2.  MOA

 

3.  Advantage over External beam radiation

Definition

1.  Brachytherapy

 

2.  Place radioactive container into tumor or cavity close to tumor

 

3.  Less body exposure, but you can get really high doses in a localized area that would be contraindicated ina  larger area

Term

1.  Define Interstitial Radiation in internal radiation therapy

 

2.  Define Intracavitary radiation in internal radiation therapy

 

Definition

1.  Radiation source is placed direclty into or next to the tumor using small pellets, seeds, wire, tubes, or containers

 

2.  Container of radioactive material placed in cavity of the body such as chest, uterus, or vagina

Term

Radiopharmaceuticals

 

1.  Define

 

2.  What do you give for bone pain/metastasis (2)

Definition

1.  Drugs containing radioactive materials that can be given IV, orally, or into a body cavity

 

2.  Strontium 89 and samarium 153 b/c they localize in the bone after being given IV

Term

Radiotherapy Thyroid Cancer

 

1.  Drug of choice

 

2.  When is it used

 

3.  Potential long term risks (2)

Definition

1.  Radioiodine or Iodine 131

 

2.  After surgery to destroy any lingering cells that have spread to lymph nodes

 

3.  Infertility in men, slite increased risk of leukemia

 

*Women wait 1 year after tx before becoming pregnant

Term

Phosphorous 32

 

1.  Most common use

 

2.  Rare uses (2)

Definition

1.  Put inside brain tumors that are cystic (hollow) to avoid killing healthy brain

 

2.  Given IV for polycythemia vera

Peritoneal cavity for ovarian cancer

Term

Radio-labeled antibodies

 

1.  Advantage

 

2.  Use

Definition

1.  Targeted delivery of radiopharamceuticals

 

2.  non-Hodgkin lymphomas

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