MUDr. Dana Maňasková

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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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O úroveň výše

Poslední aktualizace: 17. 3. 2018 18:12:58
© Dana Maňasková, metabalance.cz
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