Drugs With Cardiotoxicity Flashcards
Main drag cuisine cardiotoxicity
Cytotoxic drugs
Type of cytotoxic drugs with cardiotoxicity effect
Anthracyclines Taxoids 5-fluorouracil Cisplatin Trastuzumab
Anthracycline Cardiotoxicity effects
Cardiomyopathy
congestive heart failure
ECG alterations
Early onset effects of anthracyclines occur within
1year
In children for anthracyclines which one is more common late onset or early onset clinical cardiotoxicity
Late onset more frequent
Risk factors for anthracycline induced cardiotoxicity
Cumulative dose age Concominent administration with other chemotherapeutics underlying heart disease previous Radiotherapy
Most important risk factor for cardiotoxicity in anthracycline
Cumulative dose
Dose of the doxorubicin that can create cardiomyopathy and congestive heart failure
450-550 (normal is between 60-75 every 3 weeks )
Which anthracycline has a lower frequency of cardiotoxicity at therapeutic dose
epirubicin or doxorubicin?
Epirubicin
Mechanism of toxicity of Anthracyclien
Free radicals and superoxide formation
Semiquinone radical forms complex with iron -> anthracycline-iron free radicals complex -> reduces O2 -> superoxide production -> lipid peroxidation
Apoptosis
Calcium homeostasis disruption
Immunogenicity rxn
Monitoring and markers of cardiotoxicity
Echocardiogram identify myocardial dysfunction
Endomyocardial biopsy - Measure the presence and extent of fibrosis
Troponin t indicates myocardial cell damage
Prevention/treatment of anthracyclines induced cardiotoxicity
Cumulative dose imitations
Antioxidants ( not a success)
Iron chelators (Dexrazoxane - slow IV or fast infusion before treatment )
Lipid lowering agents
Liposomal drugs formulation of anthracyclines
Type of taxoids
Paclitaxel
Docetaxel
Cardiotoxic effects of paclitaxel
Brady arrythmias Tachyarrythmias AV block Cardiac ischemia Hypotension Congestive heart failure (especially when combined with doxorubicin)
Risk factors of taxoid induced cardio toxicity
Unstable angina
Severe coronary heart diseases
Congestive heart failure
Atrial fibrillation
When is paclitaxel safe to administer with cardiac risk factors
Single therapy
Paclitaxel drug solubility enhancer name
Ctenophor El
Mechanism of toxicity of taxoids
Ctenophor El causes massive histamine release
Damage via subcellular organelles
Pharmacokinetic interaction with doxorubicin (over 380). Paclitaxel decreases its hepatic elimination
What should you do if you administer taxoids with anthracycline
Lower cumulative dose of anthracyclien
5 fluorouracil cardiotoxicith mostly occur with what form of administrions
Continuous infusion
Cardiotoxic effects of 5FU
Cardiac arrythmias
Silent myocardial ischemia
Congestive heart failure
Risk factors of 5FU
Coronary artery disease
Concurrent radiotherapy
5FU MOA
Unclear Vasospasm leading to ischemia Direct toxicity on myocardium Activation of coagulation system Thrombosis of coronary artery Immunoallergic
Cyclophosohamide and ifosfamide alkylation agents MOA
Increase in free oxygen radicals
