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Heme & Lymph > Pharm- Folate & Purine Antimetabolites > Flashcards

Pharm- Folate & Purine Antimetabolites Flashcards

1
Q

Methotrexate

A

Anti-Folate Drug

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2
Q

Methotrexate Distinctions

A

MTX inhibits DHFR -> blocks synthesis of thymidine, methionine, & serine. Metabolite MTX(glu)n inhibits GAR & AICAR transformylase -> blocks synthesis of purines

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3
Q

Pemetrexed

A

Anti-folate drug

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4
Q

Pemetrexed Distinctions

A

multiple sites of action: potent inhibitor of thymidylate synthase & GAR transformylase. 1000x less potent inhibition of DHFR compared to MTX. Can circumvent MTX resistance

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5
Q

MTX Therapeutic uses

A

pediatric leukemias (ALL); primary CNS lymphoma; NHL; Choriocarcinoma (monotherapy); component of therapy in colon, GI, breast, H & N

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6
Q

Pemetrexed Therapeutic uses

A

Malignant pleural mesothelioma - rare cancer associated with asbestos exposure- combo w/ cisplatin. Also used in refractory non-small cell lung cancer (NSCLC)

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7
Q

High Dose MTX (HDMTX) Therapeutic uses

A

CNS prophylaxis in pts with leukemia & high-risk lymphoma. Dose of MTX must be followed with 2-3 day rescue with leucovorin. Rescue depends on rapid clearance of MTX by kidneys (hydration & alkaline urine)
-depleting folate to such a high degree

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8
Q

Intermediate Dose MTX Therapeutic uses

A

Malignant gestational trophoblastic disease (GTD)- ex choriocarcinoma. Pts seldom require aggressive hydration, urinary alkalinization or leucovorin rescue

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9
Q

Low dose MTX Therapeutic uses

A

intrathecal for CNS prophylaxis; iv for bladder, desmoid tumors; oral for ALL, APL

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10
Q

MTX Preg Category D- Dose Limiting Toxicity

A 
BM suppression (thrombocytopenia; neutropenia); mucositis. Toxicity profile varies with dose. 
HDMTX regimen risks renal crystalluria of MTX and renal failure. HDMTX requires leucovorin rescue
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11
Q

Pemetrexed Preg Category D- Dose Limiting Toxicity

A

BM suppression. Caution in pts with even mild, moderate renal insuff (ex: co-tx with NSAIDs)

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12
Q

Purine Antimetabolites

A

6-mercaptopurine, 6-thioguanine, Fludarabine, Cladribine

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13
Q

6-mercaptopurine & 6-thioguanine distinctions

A

inhibits purine ring biosynthesis & nucleotide interconversion -> disrupts DNA and RNA integrity

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14
Q

Fludarabine distinctions

A

tumor cell kinases convert 2-F-araA to nucleotide triphosphates -> inserted into DNA, RNA, and disrupt DNA & RNA synthesis

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15
Q

Cladribine distinctions

A

tumor cell kinases convert it to nucleotide analogs; inhibits DNA synthesis; also potent inhibitor of ribonucleotide reductase

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16
Q

6-mercaptopurine therapeutic uses

A

maintenance of remission in ALL

17
Q

6-thioguanine therapeutic uses

A

Acute non-lymphocytic leukemia (w/ daunorubicin & cytarabine)

18
Q

Fludarabine therapeutic uses

A

CLL; also effective against hairy cell leukemia, indolent NHL

19
Q

Cladribine therapeutic uses

A

Hairy cell leukemia; also effective against NHL; CLL

20
Q

6-mercaptopurine dose limiting toxicity

A

myelosuppresion; dose adjustment with allopurinol or febuxostat (xanthine oxidase inhibitor); hepatotoxicity (jaundice)

21
Q

6-thioguanine dose limiting toxicity

A

myelosuppression; hepatotoxicity with long term use

22
Q

Fludarabine dose limiting toxicity

A

myelosuppression; opportunistic infxs.

IV only to avoid intestinal bacteria generating toxic fluoroadenine

23
Q

Cladribine dose limiting toxicity

A

myelosuppression; drug fever

24
Q

High dose MTX metabolism/clearance

A

Hepatic metabolism -> renal elimination -> leads to crystalluria tubular obstruction

25
Q

pemetrexed has a neglible effect on?

A

DHFR, unlike MTX

26
Q

pemetrexed survival benefit with cisplatin in?

A

malignant pleural mesothelioma

27
Q

what inactivation 6-MP?

A

hepatic inactivation by TPMT & XO

28
Q

what activates 6-MP to TIMP?

A

HPRT in cells (tumor and normal)

29
Q

what activates TIMP to active metabolites in cells?

A

IMPDH and TMPT

30
Q

1st pass effect on 6-MP

A

sets up problem of 6-MP overexposure due to inhibition of XO by gout medications: allopurinal and febuxostat

31
Q

tumor lysis syndrome

A

hyperkalemia, hyperphosphatemia (hypocalcemia), hyperuricemia

32
Q

simultaneous admin of allopurinol and 6-MP limit what?

A

hyperuricemia which causes the urate crystal that cause damage

33
Q

6-thioguanine

A

bypasses the XO inactivation step so there are no drug interactions with XO inhibitors
-6-TG activated by HPRT, inactivated by TPMT

34
Q

cell cycle specific drugs are?

A

schedule dependent. duration and timing of drug admin affect efficacy more than dose

35
Q

vincristine neuropathy

A

more common & worse than vinblastine

Heme & Lymph (8 decks)

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