Cardiotoxic drugs

Question 1

Which drugs are cardiotoxic

Answer 1

anthracycline antineoplastic drugs
Daunorubicin. Doxorubicin. Epirubicin. Idarubicin. Mitoxantrone. Valrubicin.

Question 2

Which anthracycline antineoplastic drug is least toxic

Answer 2

• Mitoxantrone reported to have no to very little cardiotoxicity

Question 3

Toxicity mechanisms

Answer 3

• # 1: free radical generation and lipid membrane peroxidationo Cardiomyocytes with poor antioxidant defense mechanism
  o ROS damage target w/I cell → impair contractility → myocardial failure
• # 2: vacuolar degeneration of myocytes from SR distensiono Permanent alteration in Ca2+ release channels in SR
   Initial desensitization of channels to Ca2+
   Continued sensitization → progressive/irreversible ↓ # of functional channels

Question 4

Toxicity depends on

Answer 4

• Dose-dependent and irreversible
  o Acute toxicosis: transient ventricular arrhythmias during IV infusion
   Spontaneous release of catecholamines and histamine
   Generally no clinical significance
  o Most common at cumulative doses >250mg/m2
   Can occur from 150mg/m2
   Low cumulative doses can only cause ECG changes

Question 5

Risks factors of developing toxicity

Answer 5

 Total cumulative dose > high peak serum levels
 Concurrent administration of other cardiotoxic drugs → Cyclophosphamide
 Age: very young or old age → ↑ risk)
 Hx of cardiac dz

Question 6

Other options if toxicity

Answer 6

o Less cardiotoxic agent: mitoxantrone
o Dexrazoxane IV: iron chelator → ↓ risk of cardiotoxicosis

Question 7

Effects on heart structure and function

Answer 7

• Lesions more important in subendocardial LVFW and IVS
  o Myocyte degeneration
   Myofibrillar loss
   Cytoplasmic vacuolization
   Myocytolysis
  o Interstitial fibrosis + edema
• Myocardial failure

Question 8

Dx of toxicity: ECG

Answer 8

o ST segment/T wave changes
o ↓QRS voltage
o Conduction abnormalities
o Atrial/ventricular arrhythmias

Question 9

Dx of toxicity: CTX

Answer 9

DCM and CHF

Question 10

Dx of toxicity: Echo

Answer 10

consistent with DCM
o ↑LVIDs and LVIDd
o ↓FS%: Avoid doxorubicin in FS <20%
o LAE

Question 11

Dx of toxicity: tx

Answer 11

standard CHF tx
o Time to onset of CHF is variable