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LHT1 > Alkylating agents, cell cycle non specific drugs > Flashcards

Alkylating agents, cell cycle non specific drugs Flashcards

1
Q

cell cycle specific drugs are what?

A

schedule dependent!

-duration and timing of drug admin is more important than dose!!

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2
Q

slow growing tumors in Go (exited cell cycle)- are what?

A

-cell cycle non-specific drugs- dose-dependent!!!

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3
Q

Drugs that Alkylate DNA- 2 mech’s

A
  • cross-link DNA

- insert a methyl or ethyl molecule into DNA

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4
Q

Triazenes- distinction, drugs

A 
DNA alkylation- methylation!!
-Dacarbazine
-Procarbazine
-Temozolomide
(DPT)
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5
Q

Nitrosoureas- distinction, drugs

A

DNA alkylation/cross-linking; protein carbamylation

  • Carmustine
  • Lomustine
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6
Q

Dacarbazine- therapeutic use

A

-melanoma

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7
Q

Procarbazine- therapeutic use

A

-glioma

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8
Q

Temozolomide- therapeutic use

A

-glioma and astrocytoma

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9
Q

Carmustine and Lomustine- therapeutic use

A

brain tumors!

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10
Q

Streptozocin- therapeutic use?

A
  • selective at islet B cells

- insulinomas!

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11
Q

Nitrogen Mustards- distinction, drugs

A 
crosslinks DNA
-Cyclophosphamide
-Ifosfamide
-Mechlorethamine (vesicant)
(CIM)
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12
Q

Melphalan (nitrogen mustard)- distinction

A

-targeted to phenylalanine transporters

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13
Q

Chlorambucil (nitrogen mustard)- distinction

A

oral drug

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14
Q

Busulfan (nitrogen mustard)- distinction

A

alkyl sulfonate

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15
Q

Estramustine (nitrogen mustard)- distinction

A

Anti-androgen and alkylation

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16
Q

cross-linking agents are what?

A

cell cycle non-specific!!

  • if cant repair- tumor dies- benefit!!
  • if can repair- tumor lives- may have acquired new mutations- risk
17
Q

selectivity and resistance to DNA alkylating/cross linking agents

A
  • DNA repair capability

- multidrug resistance

18
Q

Mechlorethamine- distinction

A

-instantaneous act by water upon infusion- vesicant!- can cause blisters!!!!!

19
Q

Cyclophosphamide- moa

A
  • act by liver
  • Acrolein- urotoxic metabolite- in bladder
  • Phosphoramide mustard- active metabolite- in tumor
20
Q

Ifosfamide- moa

A
  • act by liver
  • Acrolein- urotoxic metabolic- in bladder
  • isophosphoramide mustard- active metabolite- in tumor
  • chloroacetaldehyde- neurotoxicity
21
Q

used for hemorrhagic cystitis caused by Acrolein

A

MESNA!!

-SE- hypersensitivity rxn

22
Q

Estramustine- specially used for?

A

castration-resistant prostate cancer! (anti-androgenic effects)
-however, inc risk of arterial and venous thromboembolic events

23
Q

Nitrosoureas- dual actions

A
  • DNA alkylation

- Protein modification

24
Q

Nitrosoureas that penetrate CNS

A

-Carmustine (IV)
-Lomustine (po)
used for brain cancers!!

25
Q

Triazenes- drugs

A
  • Dacarbazine
  • Procarbazine
  • Temozolomide
26
Q

Dacarbazine vs Temozolomide

A
  • Dacarbazine- IV- doesnt penetrate CNS

- Temozolomide- PO- penetrates CNS!!- astrocytoma, glioblastoma

27
Q

what influences the efficacy of Temozolomide?

A
  • MGMT status- if low expression, DNA damage causes apoptosis- tumor is susceptible
  • epigenetic silencing of MGMT- marker for efficacy
28
Q

Cisplatin- related compounds

A
  • Cisplatin- stable in plasma and high Cl- milieu
  • Carboplatin
  • Oxaloplatin
29
Q

Cisplatin- therapeutic use, dose limiting toxicity

A
  • testicular cancer (with bleomycin, vinblastine, or etoposide), ovarian cancer
  • nephrotoxicity, ototoxicity (acoustic n damage)!!
30
Q

Carboplatin- therapeutic use, dose limiting toxicity

A
  • ovarian cancer

- neutropenia

31
Q

Oxaloplatin- therapeutic use, dose limiting toxicity

A
  • colorectal cancer

- neuropathy- cold induced!

32
Q

Cisplatin- moa

A

-forms intra-strand crosslinks- poorly repaired

33
Q

cisplatin- mech of resistance

A
  • dec uptake or inc efflux
  • glutathione (causes neutralization)
  • inc DNA repair
  • defective apoptosis

LHT1 (6 decks)

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