Drug with high cardiotoxicity (8/15)
8. Antiviral and Antimicrobial Drugs
- Protease inhibitors (e.g., ritonavir, lopinavir) used in HIV treatment can cause dyslipidemia (high cholesterol) and increase the risk of coronary artery disease.
Protease Inhibitors (PIs):
Protease inhibitors block the HIV-1 protease enzyme, preventing the maturation of the virus. However, they also interfere with lipid metabolism, leading to dyslipidemia and insulin resistance.
Dyslipidemia: Protease inhibitors can significantly raise LDL cholesterol and triglycerides, while lowering HDL cholesterol, increasing the risk of atherosclerosis and coronary artery disease.
Insulin Resistance and Type 2 Diabetes: These metabolic changes increase the risk of cardiovascular diseases, including heart attack and stroke.
Coronary Artery Disease (CAD): Patients on long-term protease inhibitors are at increased risk for developing CAD due to the combination of dyslipidemia, insulin resistance, and endothelial dysfunction.
Lipid panels, glucose levels, and blood pressure should be regularly monitored. Lifestyle interventions and possibly lipid-lowering therapies may be required to mitigate these risks.
- Macrolide antibiotics and Fluoroquinolones are known to prolong the QT interval, increasing the risk of torsades de pointes.
Macrolide Antibiotics (e.g., azithromycin, erythromycin):
Macrolides inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. However, they also block potassium channels in the heart, potentially affecting the QT interval.
QT Prolongation: Macrolides can cause QT prolongation, leading to torsades de pointes, especially in patients taking other QT-prolonging medications or those with electrolyte imbalances.
Increased Risk of Cardiovascular Death: Studies have shown a potential increased risk of cardiovascular death, particularly with azithromycin, due to arrhythmias.
Drug Interactions: Macrolides interact with several other drugs that can affect heart function, including statins, calcium channel blockers, and other QT-prolonging agents.
ECGs are recommended in patients on prolonged courses or those taking other medications that affect the QT interval. Monitoring potassium and magnesium levels is also important, especially in patients with risk factors for arrhythmias.
Fluoroquinolones (e.g., ciprofloxacin, levofloxacin):
These antibiotics inhibit bacterial DNA gyrase and topoisomerase IV, but they can also affect cardiac ion channels.
QT Prolongation: Fluoroquinolones have been linked to prolonged QT intervals on the ECG, which increases the risk of torsades de pointes, a life-threatening ventricular arrhythmia.
Tendonitis and Tendon Rupture: Though primarily a musculoskeletal issue, tendon damage can limit mobility and physical activity, indirectly increasing cardiovascular risk due to a sedentary lifestyle.
ECG monitoring in patients with pre-existing QT prolongation or those taking other QT-prolonging drugs. Avoiding fluoroquinolones in patients with significant cardiovascular risks is recommended.
Ensuring cardiac safety is essential to increasing the
success rate of new drug development.
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