Drug with high Cardiotoxicity (9/15)

9. Antibiotics

Macrolides (e.g., azithromycin, erythromycin)

• Mechanism:

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.

• Risks:

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.

• Monitoring:

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.

Aminoglycosides (e.g., gentamicin, tobramycin):

• Mechanism:

Aminoglycosides inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit. However, they can also impact the heart indirectly through nephrotoxicity and electrolyte imbalances.

• Risks:

Nephrotoxicity: Aminoglycosides can damage the kidneys, leading to electrolyte disturbances (e.g., hypokalemia, hypomagnesemia) that can predispose patients to arrhythmias.

Ototoxicity: While not directly related to cardiovascular function, hearing loss from ototoxicity can affect balance, which could impact physical activity levels and indirectly influence cardiovascular health.

Hypotension: In severe cases, aminoglycosides can cause vasodilation and hypotension, leading to reduced perfusion to the heart.

• Monitoring: Kidney function and electrolyte levels should be closely monitored, especially in patients on high doses or those with pre-existing kidney issues. Regular ECGs are recommended in patients at risk of arrhythmias due to electrolyte disturbances.

Ensuring cardiac safety is essential to increasing the 
success rate of new drug developments.
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