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65 Cards in this Set
- Front
- Back
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Pt tx w chemo for Hodgkins develops symptoms of symptoms of schizophrenia - which drug?
–vincristine, nitrogen mustard, prednisone, combination or another drug? |
Answer=prednisone
(==>CNS toxicity=psychosis) NOT THE ANSWER: -vincristine=neurotoxicity (areflexia, peripheral neuritis) limits useflness -nitrogen mustards=alkylate DNA (Rx=M2C2: mechlorethamine, melphalan, cyclophosphamide, chlorambucil) |
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cancer cells lacking HGPRT are resistant to wht Rx?
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*6-mercaptoPURINE (6-MP)
*6-thioguanine (6-TP) [guanine is a PURINE] (antimetabolites; thus S-phase specific) *HGPRT (purine salvage pathway) converts these drugs into their active forms, which inhibit purine synthesis ==>inhibit DNA/RNA syn |
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cyclophosphamide
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(cell cycle non-specific <== alkylating agent)
Tx: -non-Hodgkins lymphoma -ovarian and breast carcinomas MOA: *activated by CYP450 (thus must have working liver) *alkylating agent *covalently X-links DNA strand at guanine N-7 S/E: -myelogenous (granulocytic) leukemia -acute hemorrhagic cystitis (urinary bladder)==>prevent with mesna (Alkylating agents): -moderate BM depression -large doses==>severe BM depression with: *leukopenia *thrombocytopenia *bleeding -allopurinol prolongs half-life of cyclophosphamide (MOA is unknwon) -Thus, when person is taking allopurinol, must reduce cyclophosphamide dose to 25% of nl. |
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pt tx with chemo with cyclophosphamide. pt also tx with drug for gout. what Rx incr toxicity of cyclophosphamide?
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-allopurinol
-Cyclophosphamide is metabolized by xanthine oxidase, which is inhibited by allopurinol. -Thus, if you take allopurinol ==>less xanthine oxidase ==>can't eliminate cyclophosphamide ==>cyclophosphamide toxicity: -myelongeous (grnaulocytic) leukemia -acute hemorrhagic cystitis *Thus, when person is taking allopurinol, must reduce cyclophosphamide dose to 25% of nl. |
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pt taking azathioprine and drug for gout. what should you do?
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azathioprine is metabolized to 6-mercaptopurine, which is metabolized by xanthine oxidase. Sice allopurinol inhibits xanthine oxidase, can't elim 6-MP.
*Thus, when person is taking allopurinol, must reduce azathioprine dose to 25% of nl. |
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pt taking 6-mercaptopurine and drug for gout. what should you do?
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(drug for gout=allopurinol, which inhibits xanthine oxidase)
azathioprine is metabolized to 6-mercaptopurine, which is metabolized by xanthine oxidase. Since allopurinol inhibits xanthine oxidase, can't elim 6-MP. *Thus, when person is taking allopurinol, must reduce azathioprine dose to 25% of nl. |
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allopurinol
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Tx: prevent hyperuricemia after tx of hematologic cancers
MOA: inhibits xanthine oxidase to prevent formation of urice acid S/E: -inhibits the metabolism of 6-mercaptopurine (6-MP) by xanthine oxidase ==>reduce dose of 6-MP to 25% of normal dose in patients on allopurinol -need to reduce dose of immunosuppressive drug azathioprine by 25% of normal when given to a patient taking allopurinol because azathioprine is metabolized to 6-MP |
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paclitaxel
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Tx: ovarian and breast CA
*M phase cell cycle specific MOA: binds microtubules and hyperstabilizes them ==>microtubules cannot be broken down during anaphase ==>mitotic arrest S/E: -peripheral neuropathy -BM dep |
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Dactinomycin (Actinomycin D)
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*cell cycle non-specific (<==antibiotics like dactinoMYCIN, doxorubICIN, bleoMYCIN)
mneum: "ACTinomycin used in kids b/c kids ACT out ==>thus Tx: *Wilm’s tumor *rhabdomyosarcoma *Ewing’s sarcoma “You must BIND G (Greg) and C (Charles) tightly, or else those kids will act out." MOA: binds tightly to ds DNA b/w G and C pairs ==>inhibits all DNA-dependent RNA-synthesis, esp mRNA synthesis S/E: BM depression |
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doxorubicin
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*cell cycle non-specific (<==antibiotics like dactinoMYCIN, doxorubICIN/daunorubICIN, bleoMYCIN)
=anthracycline AB (doxoRUBICIN & daunoRUBICIN) MOA: intercalates into DNA==> inhibits DNA syn S/E: forms free radicals ==>cardiotoxicity ("RUBI": heart is red) -red urine (not hematuria) [doxoRUBIcin=red) -BM dep |
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daunorubicin
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cell cycle non-specific (<==antibiotic)
=anthracycline AB (doxoRUBICIN & daunoRUBICIN) Tx: Hodgins sarcomas MOA: intercalates into DNA==> inhibits DNA syn S/E: forms free radicals ==>cardiotoxicity ("RUBI": heart is red) |
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methotrexate
-Tx? -etc |
*S phase specific (antimetabolite)
Tx: *leukemia *sarcoma -forms polyglutamate adduct, which is imp for duration of action MOA: inhibits DHFR==>can't regen THF ==>inhibits synthesis of thymidylate, purines, and the AA's serine and methionine ==>inh syn of DNA, RNA, & proteins -Resistance to methotrexate d/t: -altered DHFR -incr DHFR -decr drug transport -decr polyglutamate formation S/E: -BM depression==>use leucovorin for BM rescue |
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Clinical: A patient tx w methotrexate develops bone marrow depression. How to tx?
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leucovorin (=folinic acid) rescues BM. nl cells take up leucovorin (rescuing them), but tumor clels cannot
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5-fluorouracil
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*S cycle specific (antimetabolite)
Tx: colon cancer mneum: "put your FU-TS in a dUMP (colon: you take a dUMP out of your colon) MOA: 5-FU converted to 5-dUMP ==>inhibit thymidylate synthetase ==>no dTMP ==>no thymidine for DNA syn ==>cell death *no leucovorin rescue! S/E: -oral & GI ulceration (mneum: use "flour"ide on your teeth (oral)) |
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pt on chemo has cough w crackles, X-ray shows diffuse basilar infiltrates, drug =?
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bleomycin (Bleomycin "blasts" the lung)
G2 specific MOA: forms free radicals ==>DNA fragmentation (breaks, gaps, "Bleomycin BLASTS DNA into fragments") ==>cells accumulate in G2 and do not proceed to M S/E: -pulm fibrosis ("bleomycin blasts the lung") -little BM toxicity! |
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Drug w antiestrogenic effects for tx of breast cancer = ?
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tamoxifen
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carmustine
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*cell cycle non-specific (<==alkylating agents)
carMUSTIne & loMUSTIne (nitrosureas) mneum: "as you sit inside your car while it runs, the CAR's MUSTIness (fumes like CO) cross your BBB ==>kill brain tumors, but gives you CNS toxicity (ataxia, dizziness) MOA: *cross-links DNA via alkylation *requires bioactivation |
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lomustine
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*cell cycle non-specific (<==alkylating agents)
carMUSTIne & loMUSTIne (nitrosureas) mneum: "as you sit inside your car while it runs, the CAR's MUSTIness (fumes like CO) cross your BBB ==>kill brain tumors, but gives you CNS toxicity (ataxia, dizziness) MOA: *cross-links DNA via alkylation *requires bioactivation |
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what type of receptors must be present to Tx breast cancer w/leuprolide and goserelin?
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must have estrogen receptors in tumor tissue
GnRH analogs (leuprolide & goserelin) given in continuous manner ==>inhibit release of LH/FSH from pit ==>decr LH ==>decr estrogen synthesis by ovaries ==>less stimulation of tumor |
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cisplatin
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*cell cycle non-specific (<==alkylating agents, ~cyclophosphamide)
Tx: testicular and lung CA MOA (~cyclophosphamde) hydrolyze Cl groups ==>forms intra- and interstrand cross links at N7 of guanine ==>replacement of Cl with water forms the active drug S/E: *nephrotoxicity==>loss of Mg++, Ca++, K++, and phosphate *decr nephrotoxicity by inducing Cl diuresis (since Cl- stabilizes the drug's platin complex) *acoustic nerve dysfunction |
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prednisone:
-which cancers does it Tx? -MOA? |
prednisone
Tx: CLL, Hodgkin's MOA: apoptosis in non-dividing cells |
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radiation and alkylating agnets
-how incr tumor cell death |
-incr tumor cell death by incr dose antimetabolites
-incr tumor cell death by incr exposure time, not hte dose |
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what are the alkylating agents?
-what S/E? |
A. ALKYLATING AGENTS=
1. Nitrogen mustards; mneum: "C2M2"= -cyclophosphamide -CHLORambucil -meCHLORethamine -melphalan 2. nitrosureas (carMUSTine, loMUSTine) 3. busulfan 4. cisPLATIN, carboPLATIN S/E of Alkylating agents: -moderate BM depression -large doses==>severe BM depression with: *leukopenia *thrombocytopenia==>bleeding |
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large doses of this Rx causes severe BM depression with:
*leukopenia *thrombocytopenia *bleeding |
A. ALKYLATING AGENTS=
1. Nitrogen mustards; mneum: "C2M2"= -cyclophosphamide -CHLORambucil -meCHLORethamine -melphalan 2. nitrosureas (carMUSTine, loMUSTine) 3. busulfan 4. cisPLATIN, carboPLATIN |
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S/E:
-pulm fibrosis -hyperpigmentation -adrenal insufficiency |
busulfan (Tx CML)
(adrenal insufficiency ==>decr cort ==>incr ACTH ==>hyperpigmentation) |
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S/E hemorrhagic cystitis
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cyclophosphamide, tx with mesna
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S/E:
renal damage acoustic nerve damage |
cisplatin
"ciSPLATin (and carboPLATIN make your kidney & ears go SPLAT" |
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S/E:
acoustic nerve damage |
cisplatin
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S/E:
renal damage |
cisplatin
S/E: *acoustic nerve damage *renal damage ==>incr excretion of Ca, Mg, K, phosphate ~Can decr renal damage from CispLatin via Cl diuresis (Cl stabilizes the drug's platin complex) |
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S/E procarbazine
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CNS depression
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S/E:
CNS depression |
procarbazine
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S/E:
psychosis |
glucocorticoids (prednisone)
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S/E: oral and GI ulceration
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5-fluorouracil (5-FU)
imagine a foot (FU-TS) violently kicking your oral and GI mucosa, creating ulcers |
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S/E: pulm fibrosis
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bleomycin,
busulfan "bleomycin & busulfan blast the lungs" |
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S/E: BM depression
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A. Hydroxyurea (S phase specific)
B. etoposide (S & G2 phase specific) C. paclitaxel (taxol) (M phase specific) D. ALKYLATING AGENTS (cell cycle non-specific) 1. Nitrogen mustards; mneum: "C2M2"= -CYCLOPHOSPHAMIDE -CHLORambucil -meCHLORethamine -melphalan 2. nitrosureas (carMUSTine, loMUSTine) [~cyclophosphamide) 3. busulfan 4. cisPLATIN, carboPLATIN E. ANTIBIOTICS (cell cycle non-specific): -dactinomycin -doxorubicin/daunorubicin |
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S/E:
-cardiac toxicity |
doxoRUBIcin/daunoRUBIcin (heart is red)
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S/E:
-red urine (not hematuria) |
doxoRUBICin
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S/E of vincristine
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areflexia
peripheral neuritis musc weakness paralytic ileus alopecia ("Vincristine is more subtle. She doesn't blast the BM like vinblastine does.") |
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S/E of vinblastine
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-BM depression
-loss of reflexes -areflexia (Jeff: "vinBLASTine BLASTS the BM & reflexes (the explosion behind her as she walks to her Porsche) |
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S/E: incr risk of endometrial cancer
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tamoxifen
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S/E: menopausal Sx
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tamoxifen
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S/E of tamoxifen
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-incr risk of endometrial cancer
-menopausal Sx |
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what is the S-phase specific drug that inhibits DNA poly
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cytarabin (C-ara)
MOA: C-ara is incorporated as ara-CTP and thus inhibits DNA elongation *cytarabine (via deoxycytidine kinase) ==>AraCMP ==>AraCTP |
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G1-phase specific drugs
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none
[G1 phase synthesizes compounds needed to synthesize DNA in S phase, which comes right after G1] |
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S-phase specific drugs
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block in S phase
="antimetabolites" =prevent DNA replic and repair 1. hydroxyurea (inhibit ribonucleotide reductase) 2. 5-FU [fluorouracil] (inhibit thymidylate synthase) 3. 6-MP [mercaptopurine] & 6-TP (inhibit purine synthesis) 4. methotrexate (inhibit DHF-R) 5. cytarabine [Ara-C] (prevents DNA elongation by incorporating AraCTP) |
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G2-phase specific drugs
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block G2= block synthesis of molecules req for mitosis
1. bleomycin -form free radicals ==>"blasts" DNA into fragments ==>DNA fragmentation 2. eTOPOside: -stabilizes bond b/w TOPOII and DNA ==>inhibits TopoII ==>DNA breaks remain ==>cannot proceed to mitosis [TopoI and TopoII unwind the ds DNA to repair it)] |
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M-phase specific drugs
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1. vincristine/vinblastine:
bind tubulin ==>cannot assemble microtubules ==>mitotic filaments cannot form 2. paclitaxel & other taxols: hyperpolymerizes microtubules ==>microtubules cannot break down during anaphase ==>stops mitosis |
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cell cycle specific drugs
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S phase specific:
1. hydroxyurea 2. 5-FU 3. 6-MP, 6-TP 4. methotrexate 5. cytarabine [Ara-C] G2 phase-specific: 1. bleomycin 2. etoposide M phase-specific: 1. vincristine/vinblastine 2. paclitaxel (and other taxols) |
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cell cycle non-specific
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A. ALKYLATING AGENTS=
1. Nitrogen mustards; mneum: "C2M2"= -cyclophosphamide -CHLORambucil -meCHLORethamine -melphalan 2. nitrosureas (carMUSTine, loMUSTine) 3. busulfan 4. cisPLATIN, carboPLATIN B. ANTIBIOTICS -dactinoMYCIN -plicaMYCIN -doxoRUBICIN/daunoRUBICIN (exception: bleoMYCIN=G2 phase specific) C. glucocorticoids D. dacarbazine/procarbazine Cell cycle non-specific Rx: -can work at any phase of cell cycle, incl Go -cells are more sensitive in late G1-S phases b/c polynucleotides are more susceptible to alkylation in unpaired state than in helical form -toxicity usu occurs when cells enter S phase and progression thru cell cycle is blocked -ex. doxorubicin-intercalates into DNA ==>DNA strand scission (single and double strand breaks) via inhibition of TopoII (cells die in G2) |
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Tx:
-non-Hodgkins lymphoma -ovarian and breast carcinomas |
cyclophosphamide
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Tx: prevent hyperuricemia after tx of hematologic cancers
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allopurinol
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Tx: Wilm's tumor
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Dactinomycin (Actinomycin D)
mneum: "ACTinomycin used in kids b/c kids ACT out. You must BIND G (Greg) and C (Charles) tightly, or else those kids will act out." *cell cycle non-specific (<==antibiotics like dactinoMYCIN, doxorubICIN, bleoMYCIN) MOA: binds tightly to ds DNA b/w G and C pairs ==>inhibits all DNA-dependent RNA-synthesis, esp mRNA synthesis S/E: BM depression |
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Tx:
Hodgkins |
Doxorubicin/daunorubicin
Tx: Hodgkins sarcomas |
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Tx:
sarcomas |
Doxorubicin/daunorubicin
Tx: Hodgkins sarcomas |
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Tx:
*leukemia |
Methotrexate
*S phase specific (antimetabolite) Tx: *leukemia *sarcoma -forms polyglutamate adduct, which is imp for duration of action MOA: inhibits DHFR==>can't regen THF ==>inhibits synthesis of thymidylate, purines, and the AA's serine and methionine ==>inh syn of DNA, RNA, & proteins -Resistance to methotrexate d/t: -altered DHFR -incr DHFR -decr drug transport -decr polyglutamate formation S/E: -BM depression==>use leucovorin for BM rescue |
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Tx: sarcoma
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1. Doxorubicin/daunorubicin
Tx: Hodgkins sarcomas Or 2. Methotrexate *S phase specific (antimetabolite) Tx: *leukemia *sarcoma -forms polyglutamate adduct, which is imp for duration of action MOA: inhibits DHFR==>can't regen THF ==>inhibits synthesis of thymidylate, purines, and the AA's serine and methionine ==>inh syn of DNA, RNA, & proteins -Resistance to methotrexate d/t: -altered DHFR -incr DHFR -decr drug transport -decr polyglutamate formation S/E: -BM depression==>use leucovorin for BM rescue |
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Tx: colon cancer
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5-flourouracil
*S cycle specific (antimetabolite) Tx: colon cancer mneum: "put your FU-TS in a dUMP (colon: you take a dUMP out of your colon) MOA: 5-FU converted to 5-dUMP ==>inhibit thymidylate synthetase ==>no dTMP ==>no thymidine for DNA syn ==>cell death *no leucovorin rescue! S/E: -oral & GI ulceration (mneum: use "flour"ide on your teeth (oral)) |
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Tx: testicular CA
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Cisplatin
*cell cycle non-specific (<==alkylating agents, ~cyclophosphamide) Tx: testicular and lung CA MOA (~cyclophosphamde) hydrolyze Cl groups ==>forms intra- and interstrand cross links at N7 of guanine ==>replacement of Cl with water forms the active drug S/E: *nephrotoxicity==>loss of Mg++, Ca++, K++, and phosphate *decr nephrotoxicity by inducing Cl diuresis (since Cl- stabilizes the drug's platin complex) *acoustic nerve dysfunction: "ciSPLATin (and carboPLATin) make your kidneys and ears go SPLAT" |
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Tx: lung CA
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Cisplatin
*cell cycle non-specific (<==alkylating agents, ~cyclophosphamide) Tx: testicular and lung CA MOA (~cyclophosphamde) hydrolyze Cl groups ==>forms intra- and interstrand cross links at N7 of guanine ==>replacement of Cl with water forms the active drug S/E: *nephrotoxicity==>loss of Mg++, Ca++, K++, and phosphate *decr nephrotoxicity by inducing Cl diuresis (since Cl- stabilizes the drug's platin complex) *acoustic nerve dysfunction |
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Tx: CLL
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prednisone (the PREsiDent's SON, George W. Bush, wants to win votes of the rich elderly so he cures elderly people's leukemia (CLL, >60 y/o) & lymphoma (Hodgkin's lymphoma [vs. Non-Hodgkins which AIDS pts get b/c he doesn't want to help them])
Tx: CLL, Hodgkin's MOA: apoptosis in non-dividing cells |
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Tx: Hodgkins
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Doxorubicin/daunorubicin:
Tx: Hodgkins sarcomas or Prednisone Tx: CLL, Hodgkin's MOA: apoptosis in non-dividing cells |
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Tx CML
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Imatinib (Gleevec):
Philadelphia chromosone brc-abl tyrosine kinase inhibitor or busulfan (Tx CML) (adrenal insufficiency ==>decr cort ==>incr ACTH ==>hyperpigmentation [mneum: hyperpigmented spots that smell like rotten eggs--sulfur (bulSULFan)] S/E: -pulm fibrosis -hyperpigmentation -adrenal insufficiency |
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Tx rhabdomyosarcoma
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Dactinomycin (Actinomycin D)
mneum: "ACTinomycin used in kids b/c kids ACT out ==>thus Tx: *Wilm’s tumor *rhabdomyosarcoma *Ewing’s sarcoma “You must BIND G (Greg) and C (Charles) tightly, or else those kids will act out." *cell cycle non-specific (<==antibiotics like dactinoMYCIN, doxorubICIN, bleoMYCIN) MOA: binds tightly to ds DNA b/w G and C pairs ==>inhibits all DNA-dependent RNA-synthesis, esp mRNA synthesis S/E: BM depression |
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Tx Ewing's sarcoma
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Dactinomycin (Actinomycin D)
mneum: "ACTinomycin used in kids b/c kids ACT out ==>thus Tx: *Wilm’s tumor *rhabdomyosarcoma *Ewing’s sarcoma “You must BIND G (Greg) and C (Charles) tightly, or else those kids will act out." *cell cycle non-specific (<==antibiotics like dactinoMYCIN, doxorubICIN, bleoMYCIN) MOA: binds tightly to ds DNA b/w G and C pairs ==>inhibits all DNA-dependent RNA-synthesis, esp mRNA synthesis S/E: BM depression |
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what anti-cancer drug must be activated to a ribonucleotide before it's active?
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6-mercaptopurine
activated by HGPRTase |
