Cardiac toxicity

Mechanisms of Cardiotoxicity Chemical compounds often affect the cardiac conducting system and thereby change cardiac rhythm and force of contraction. These effects are seen as alterations in the heart rate, conduction velocity of impulses within the heart, and contractivity. For example, alterations of pH and changes in ionic balance affect these cardiac functions. In principle, cardiac toxicity can be expressed in three different ways (1) pharmacological actions become amplified in an nonphysiological way (2) reactive metabolites of chemical compounds react covalently with vital macromolecules... 

Halogenated hydrocarbons depress cardiac contractility, decrease heart rate, and inhibit conductivity in the cardiac conducting system. The cardiac-toxicity of these compounds is related to the number of halogen atoms it increases first as the number of halogen atoms increases, but decreases after achieving the maximum toxicity when four halogen atoms are present. Some of these compounds, e.g., chloroform, carbon tetrachloride, and trichloroethylene, sensitize the heart to catecholamines (adrenaline and noradrenaline) and thus increase the risk of cardiac arrhythmia. 

The relative eontribution of different mechanisms to stimulant-induced cardiac toxicities is not known. Currently, sympathetic overstimulation is thought to mediate many of these effects (Cregler and Mark 1986). 

Cardiotoxicity is a serious, rare adverse effect of mitox-antrone. The incidence of congestive heart failure was 0.15% in patients with normal left ventricular ejection fraction and 2.18% in those who had asymptomatic left ventricular ejection fraction of less than 50% at baseline.46 Therefore, mitoxantrone should not be used in patients with baseline cardiomyopathy, even if asymptomatic. The risk of cardiotoxicity is dose-related. The maximum lifetime dose of mitoxantrone is 140 mg/m2, or about 3 years of MS therapy. The use of cyclooxygenase-2 inhibitors should be avoided in patients receiving mitoxantrone because of a potential for worsening cardiac toxicity.46... 

Each category of chemotherapy drugs has similar side effects. Anthracyclines cause cardiac toxicity, which is related to the cumulative dose. Tubulin interactive agents are associated with neuropathy and ileus. Alkylating agents are associated with secondary malignancies. 

This royal-blue-colored drug is an anthracenedione that inhibits DNA topoisomerase II. The pharmacokinetics of mitoxantrone may best be described by a three-compartment model, with an a half-life of 3 to 10 minutes, a 3 half life of 0.3 to 3 hours, and a median terminal half-life of 12 days. Biliary elimination appears to be the primary route of elimination, with less than 10% of the drug eliminated by the kidney.23 Mitoxantrone has shown clinical activity in the treatment of acute leukemias, breast and prostate cancer, and non-Hodgkin s lymphomas. Myelosuppression, mucositis, nausea and vomiting, and cardiac toxicity are side effects of this drug. The total cumulative dose limit is 160 mg/m2 for patients who have not received prior anthracycline or mediastinal radiation. Patients who have received prior doxorubicin or daunorubicin therapy should not receive a cumulative dose greater than 120 mg/m2 of mitoxantrone. Patients should be counseled that their urine will turn a blue-green color. 

Cisplatin-docetaxel diarrhea, cardiac toxicity, renal toxicity, neuropathy, weakness, hypersensitivity reactions, anemia Infection, thromocytopenia, nausea, vomiting, diarrhea, cardiac, High (day 1 only)... 

For early-stage diffuse, aggressive NHL, combined-modality therapy was tested versus a longer course of chemotherapy.22 Overall survival favored the CHOP/radiation arm for 5 years (82% versus 72%). There was a trend toward increased toxicity, particularly hematologic and cardiac toxicity, in the CHOP alone arm. The results of this trial have established combined-modality therapy as first-line treatment for early-stage NHL. Unique presentations of NHL, such as CNS primary disease, may incorporate radiation into treatment algorithms.23... 

For doxorubicin-containing regimens, total the cumulative dosage received by the patient to monitor for cardiac toxicity. 

Myelosuppression (dose-related) mucositis (worse with continuous infusion) moderate emetogenic potential alopecia vesicant severe extravasation injury cardiac toxicities acute—not related to cumulative dose arrhythmias, pericarditis chronic— cumulative injury to myocardium (total dose greater than 550 mg/m2 lower total cumulative doses cause damage to myocardium in children (e.g., 350 mg/m2)... 

Doxorubicin—monitor cumulative dose for cardiac toxicity (not to exceed 550 mg/M2 or 450 mg/M2 with prior chest radiotherapy) vesicant—avoid extravasation use 50% for bilirubin 1.5-3.0 use 25% for bilirubin > 3.0... 

Epirubicin-monitor cumulative dose for cardiac toxicity (not to exceed 1000 mg/M2) vesicant—avoid extravasation... 

Mitoxantrone-watch cumulative dose—do not exceed 140 mg/M2 possible cardiac toxicity ... 

Anthracyclines—monitor cumulative dose for possible cardiac toxicity vesicant-avoid extravasation... 

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