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Chemotherapies - Cancer Drug List for FRCR CO1 > DNA linking agents > Flashcards

DNA linking agents Flashcards

1
Q

What are the DNA linking agents?

A
  • Carboplatin
  • Cisplatin
  • Oxaliplatin
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2
Q

What is the mechanism of action of cisplatin and carboplatin?

A

Not cell cycle specific

Bind A+G at N=7 positiion
Form inter and intra DNA strand crosslinks
DNA strand kinks and blocks

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3
Q

What is the mechnaism of drug resistance against cisplatin and oxaliplatin?

A
  • Increased inactivation by thiol-containing proteins
  • Increased DNA repair
  • dMMR
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4
Q

What does carboplatin interact with?

A
  • Paclitaxel should be given first
  • Warfarin
  • Lowers phenytoin
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5
Q

What is the absorption of carboplatin?

A

Trick Q - IV only

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6
Q

How is carbolplatin distributed?

A

Widely - crosses BB

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7
Q

How is carboplatin metabolised?

A

Intracellular hydrolysis

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8
Q

How is carboplatin excreted?

A

Renal
Half life 2-6 hours

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9
Q

What toxicities are associated with carboplatin?

A
  • Type 1 hypersensitivity reaction
  • Nephrotoxicity
  • Peripheral neuropathy
  • Ototoxicity
  • Low electrolytes
  • Thrombocytopenia
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10
Q

What does cisplatin interact with?

A
  • Paclitaxel should be given first
  • Bleomycin (lung)
  • Lowers phenytoin
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11
Q

How is cisplatin absorbed?

A

N/A IV only

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12
Q

How is cisplatin distributed?

A

> 90% plasam protein binding, does not cross BBb

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13
Q

How is cisplatin metabolised?

A

Highly protein bound

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14
Q

How is cisplatin excreted?

A

Renally
Half life 30 mins

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15
Q

What are the toxicities associated with cisplatin?

A
  • Ototoxicity
  • Nephrotoicity
  • Vascular tox
  • Peripheral neuropathy
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16
Q

How does cisplatin cause nephrotoxicity?

A
  1. PCT lesion
  2. DCT reabsorption
  3. Renal vascular resistance - reduced blood flow and GFR
  4. 75% hypomagnesaemia 3-12 weeks after therapy
17
Q

What is the mechanism of action of oxaliplatin?

A

Targets DNA polymerase - absence inhbits DNA synthesis, cell cycle arrest and apoptosis

18
Q

How does resistance to oxaliplatin happen?

A

Glutathione
MT reduces drug efficacy

19
Q

What does oxaliplatin interact with?

A

Warfarin (increased INR)

20
Q

What is the absorption of oxaliplatin?

A

N/A IV only

21
Q

What is the distribution of oxaliplatin?

A

> 90% plasma protein bound

22
Q

How is oxaliplatin metabolised?

A

Intracellular conversions

23
Q

How is oxaliplatin excreted?

A

Renal
Half life 15 minutes

24
Q

What toxicities does oxaliplatin cause?

A
  • Neurotox - peripheral neuropathy and cold dysesthesia
  • PRES
  • Deranged LFTs
  • QT prolong
  • Mild hypersens
25
Q

How does oxaliplatin cause peripheral neuropathy?

A

Impairs axonal voltage gated sodium channels using calcium ions

Chemotherapies - Cancer Drug List for FRCR CO1 (5 decks)

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