Makrolidy
Mechanismus účinku
- Macrolides including azithromycin, carbomycin A, clarithromycin, and erythromycin
- Bind within the exit tunnel of the bacterial ribosome
- Perturb peptide-bond formation and ribosomal translocation
- Inhibitory action on mitochondrial protein synthesis [1]
- Erythromycin and clarithromycin
- Can increase the risk of serious ventricular arrhythmias
- Associated with an increased risk of sudden cardiac death
- Azithromycin
- Also may have proarrhythmic effects
- At least seven published reports of patients with normal baseline QT intervals
- Azithromycin had arrhythmia-related adverse cardiac effects
- Pronounced QT-interval prolongation
- Torsades de pointes
- At least 20 reports of torsades de pointes FDA reg.
- Polymorphic ventricular tachycardia in the absence of QT-interval prolongation
- Ventricular arrhythmias reported in conjunction with azithromycin use are often rapidly fatal
- Retrospective cohort study of mortality among patients who used this antibiotic [1]
Indikace
- Infections caused by Staphylococcus aureus
- Streptococcus pneumoniae
- Streptococcus pyogenes [3]
- 14-, 15- or 16-membered lactone ring
- Carrying one or more sugar moieties and additional substitutions [3]
Nežádoucí účinky
- Macrolides belong to the polyketide class of natural products
- Presence of a macrolide ring
Srdce a mitochondrie
- Erythromycin and clarithromycin
- Rarely show QT prolongation
- Can lead to torsades de pointes
- Macrolides prolonging the QT interval inhibit the rapid component of the delayed rectifier K+ current (IKr)
- Block of potassium channels encoded by the human ether-a-go-go-related gene (HERG)
- Increased ROS generation alters the kinetics of hERG K+ conductance [3]
- Rat cardiomyocytes were isolated, mitochondria isolated
- Exposed to erythromycin, azithromycinand clarithromycin induced:
- Reactive oxygen species formation
- mitochondrial membrane permeabilization
- mitochondrial swelling
- Cytochrome crelease in cardiomyocyte mitochondria [3]
- Toxicity of heart mitochondria
- Starting point for cardiotoxic effects of macrolides including
- QT prolongation
- Torsades de pointes
- Arrhythmia [3]
Gastrointestinal disturbances
- Amotilin agonist:
- Diarrhea
- Nausea
- Abdominal pain
- Vomiting
- Very common adverse effects [3]
- Clarithromycin (6-O-methyl erythromycin)
- Respiratory infections [3]
- Skin infections and Lyme disease [3]
- Helicobactor pylori [3]
- Clarithromycin
- Can lead to prolonged QT intervals
- Who already have long QT syndrome, cardiac disease or patients simultaneously taking other QT-prolonging medications
- Can increase risk of life-threatening arrhythmias
Literatura:
[1] onlinelibrary.wiley.com/doi/10.1002/bies.201500071/full
[2] www.nejm.org/doi/full/10.1056/NEJMoa1003833#t=article
[3] www.researchgate.net/publication/278039756_Toxicity_of_macrolide_antibiotics_on_isolated_heart_mitochondria_A_justification_for_their_cardiotoxic_adverse_effect
[4]
[5] www.genetika-biologie.cz/genetika-mitochondrii
[6] ghr.nlm.nih.gov/condition/mitochondrial-encephalomyopathy-lactic-acidosis-and-stroke-like-episodes
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