Exam I - Chemotherapy Flashcards

1
Q

Drug List

A
  • Methotrexate
  • 5-FU
  • Cyclophosphamide
  • Hydroxyurea
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2
Q

Chemotherapy

Purpose

A
  • Toxicity with a purpose
  • remove target
  • ideally selectively toxic for target (bug/cancer)
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3
Q

Logarithmic Chemotx

A
  • successive treatments

- each treatment kills a PERCENTAGE

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4
Q

Normal cell populations

that actively replicate

A
  • hair
  • skin
  • blood
  • GI mucosa
  • pregancy
  • immune processes
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5
Q

Cell proliferation processes

A
  • DNA synthesis

- cell division

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6
Q

Chemotherapy

Toxicities

A
  • targets normal actively replication cells

- skin, hair, blood, GI mucosa

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7
Q

Cell-cycle specific

Examples

A
  • DNA synthesis inhibitors

- mitotic inhibitors

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8
Q

Cell cycle non-specific

Exampl

A

-alkylating agents

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9
Q

Drug Resistance

3 ways

A
  • therapy failure
  • acquired or innate
  • mutation or gene expression changes
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10
Q

Resistance Mechanisms

A
  • altered target
  • detoxifying enzymes inactivate drugs
  • decrease uptake/decrease permeability/increased efflux
  • increased target enzyme
  • increased levels of competitive substrate
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11
Q

Methotrexate

Mechanism

A

-inhibits DNA synthesis:
inhibs thymidine synth (by blocking DHFR
and depleting tetrahydrofolate)

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12
Q

Methotrexate

Indications

A
  • arthritis
  • autoimmune dz
  • cancer (at higher dose)
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13
Q

Methotrexate

ADME

A
  • oral or parenteral
  • absorbed better at low dose
  • renal elim
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14
Q

Methotrxate

Adverse

A
  • hepatotoxicity

- bone marrow/GI/urine crystals

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15
Q

Fluorouracil

Mechanism

A
  • inhibits DNA and RNA synth
  • analog of thymidine (FdUMP DNA, FdUTP RNA)
  • inhibits thymidine synth
  • inhibits thymidylate synthetase
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16
Q

Fluorouracil

ADME

A
  • topical or IV
  • metab’d extensively
  • secreted renally
17
Q

Fluorouracil

Adverse

A
  • Nausea, vomit
  • myelosuppression
  • Oral/GI ulceration
18
Q

Fluorouracil

indications

A

-topical for actinic keratoses, skin cancer

19
Q

Hydroxyurea

Mechanism

A

-inhibits DNA synthesis:
-inhibits ribonucleotide reductase
(which converts ribonucs to dexoxyribonucs)
-induces fetal Hgb (use with sickle cell)
(suppresses erythrocyte precursors)

20
Q

Hydroxyurea

ADME

A

-oral

21
Q

Hydroxyurea

Adverse

A
  • myelosuppression (pancytopenia)
  • GI disturbance
  • dermatologic rxns
  • potent teratogen
  • does NOT increase risk of leukemia in sickle cell
  • monitor neutrophil count in sickle cell tx
22
Q

Cyclophosphamide

Mechanism

A
  • alkylating agent
  • inhibits DNA synth
  • primary: cross-links DNA
  • also damages bases
  • also makes DNA-protein cross-links
23
Q

Cyclophosphamide

Indications

A
  • rheumatoid d/o
  • immunosuppression
  • autoimmune nephritis
  • bone marrow transplant
24
Q

Cyclophosphamide

ADME

A
  • Oral or IV
  • pro-drug; metab’d in liver (P450)
  • active metabolite: phosphoramide mustard
  • toxic metabolite: acrolein
25
Q

Cyclophosphamide

Adverse

A
  • alopecia
  • nause/vomit
  • myelosuppression
  • hemmorhagic cystitis (acrolein)
26
Q

Cyclophosphamide

How to combat hemorrhagic cystitis

A
  • drink lots of fluid

- MESNA-sulfhydryl reagent deactivate acrolein