DNA Alkyating Agents 2 Flashcards
What does cyclophosphamide require to be active?
Metabolic oxidation
What structure can cause hemorrhagic cystitis?
Acrolein
What enzyme makes cyclophosphamide active?
ALDH
Why are cyclophosphamide and anthracyclines not commonly seen used together?
Cyclophosphamide may potentiate the red flag cardiotoxicity
What amino acid can cause cyclophosphamide to create Acrolein?
Cysteine
What is the main ADE that cyclophosphamide can cause?
Hemorrhagic cystitis
What 4 symptoms can represent hemorrhagic cystitis?
- Dysuria
- Hematuria
- Red or orange urine
- Potentially fatal bleeding
What is a chemoprotectant used for cyclophosphamide?
MESNA
What 2 ways can you decrease the risk of cyclophosphamides ADR?
- Increase fluid intake to >2 L/day
- Take it in the morning
What is the structural isomer of cyclophosphamide?
Ifofsamide
Why is ifosfanide more toxic than cyclophosphamide?
Creates:
1. Chloroacetylaldehyde
2. Acrolein
What is ifosfamide always dispensed with?
MESNA
What dose limited side effect is seen with ifosfamide?
Encephalopathy
How can ifosfamide cause it’s dose limiting SE?
Can cross the BBB and interact with brain proteins
What is MESNA a mimic of?
Glutathione-SH
True or false: MESNA can cross the BBB
False
What can MESNA not prevent?
Encephalopathy caused by ifosfamide
Inorganic platinum is a good _______
Electrophilic atom
How are the platinum containing agents activated?
By aquation
What do the platinum agents cause in the dna?
DNA can’t unwind
How do the platinating agents enter cells?
Via copper transport protein (CRT1)
What 3 toxicities can be seen with the platinating agents?
- Ototoxicity
- Nephrotoxicity
- Peripheral sensory neuropathy
Cisplatin has the highest incidence of _________
CINV
Where can cisplatin concentrate?
In the cochlea of the ear
What should you ensure for a patient taking cisplatin?
Adequate IV hydration
What agent is notoriously associated with acute sensory neuropathy?
Oxaliplatin
What electrolyte can oxaliplatin chelate?
Calcium
How can you avoid organoplatinum complexes with the platinating agents?
Avoid administration with aluminum
What is a boxed warning for all the platinating compounds?
Anaphylactic response
What should you not administer the platinum based compounds with to avoid ototoxicity?
Aminoglycosides
