Cardiovascular Toxicity of Noncardiac Medications

68 Cardiovascular Toxicity of Noncardiac Medications



Eric H. Yang


Several noncardiac medications have deleterious effects on the cardiovascular system. These effects can be classified as transient or permanent and can result in functional and/or structural abnormalities in the heart and vasculature. Cardiotoxic drugs with permanent structural effects are the most harmful and are the focus of this chapter. Shown in Box 68-1, these drugs can be classified based on the location of their cardiotoxic effects: myocardium, valves, or coronary arteries.



Box 68-1 Classification of Cardiotoxic Medications



Myocardial Toxicity



Anthracycline derivatives

Trastuzumab

Ethanol

Chloroquine, hydroxychloroquine


Valvular Toxicity



Phentermine and fenfluramine

Ergot alkaloids
Ergotamine

Methysergide

Pergolide


Coronary Artery Toxicity



Protease inhibitors


Myocardial Toxicity



Anthracyclines


Doxorubicin, daunorubicin, and idarubicin are anthracycline chemotherapeutic agents commonly used in the treatment of a large number of malignancies. Since the first use in the 1960s, several reports have linked high doses of doxorubicin to cardiomyopathy. The cardiotoxic effects are almost certainly dose-related. Cardiomyopathy occurs in approximately 4% of patients who receive a maximum lifetime dose of 550 mg/m2 of doxorubicin or 450 mg/m2 of daunorubicin or idarubicin and in up to 18% of those treated with higher doses of the drugs. The risk of doxorubicin-induced (or daunorubicin- or idarubicin-induced) cardiomyopathy is increased in patients who are older than 70 years of age, receive radiation therapy to the chest, and/or have baseline structural heart disease. The exact mechanism of cardiotoxicity is unknown. Current thinking is that oxidative stress is increased in individuals treated with these drugs. Given its high metabolic demand, the heart is sensitive to changes in oxidative stress, and increases can result in cardiomyocyte apoptosis. The effects seem to be permanent but may be avoided with limited exposure and by pretreatment with β-blockers and angiotensin-converting enzyme inhibitors.



Trastuzumab


Approximately 25% of breast cancers overexpress the HER2 (human epidermal growth factor receptor) protein or are associated with amplification of the HER2 gene. Trastuzumab (Herceptin; Genentech, South San Francisco, CA) is a monoclonal antibody specific to the extracellular domain of the HER2 protein. When used in conjunction with conventional chemotherapy, trastuzumab improves survival in patients with breast cancer who are HER2-positive. Combined data from the initial clinical trials show that the occurrence of overt clinical heart failure is rare, but up to 14% of patients have an asymptomatic decline in their ejection fraction during therapy. The exact mechanism is unclear but appears not to involve free radical generation or oxidative stress. It has been proposed that trastuzumab may interfere with cell signaling within myocytes and inhibit the natural response to cardiac stress, which then results in an increased risk of irreversible loss of function when the myocytes are further stressed. Thus, unlike doxorubicin toxicity, trastuzumab toxicity may be reversible if the drug is discontinued early. Left ventricular function in patients receiving trastuzumab therapy should be monitored closely, and any reduction in left ventricular function should prompt consideration of whether therapy can be discontinued or delayed.

Related posts:

  1. Angiogenesis and Atherosclerosis
  2. Left and Right Heart Catheterization
  3. Interventional Approaches for Peripheral Arterial Disease
  4. Aortic Regurgitation

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Jun 12, 2016 | Posted by in CARDIOLOGY | Comments Off on Cardiovascular Toxicity of Noncardiac Medications

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