MACROLIDES AND AZALIDES Flashcards
What is the prototype drug in this group?
erythromycin
What are the two drugs within the MACROLIDES AND AZALIDES group?
erythromycin and clindamycin
What is a chemically an azalide derived from erythromycin?
azithromycin (Zithromax)
What is the preferred and constitutes the vast majority of macrolide use?
azithromycin
Due to the drug interaction and side effect profiles of erythromycin and clarithromycin,
Macrolides exhibit what kind of properties that help in their effectiveness in infections and cystic fibrosis?
exhibit immunomodulating properties
What is the MOA of macrolides and azalides?
reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating the dissociation of peptidyl-tRNA from ribosomes.
What activity do macrolides and azalides have?
Atypical and intracellular organisms commonly resistant to beta-lactam antibiotics
What activity does Clarithromycin have?
greater activity than erythromycin or azithromycin against gram-positive organisms such as Streptococcus species and MSSA
Best macrolide in treating H. influenzae?
Azithromycin
How is resistance mediated for macrolides and azalides?
(1) reduced permeability of the cell membrane or active efflux,
(2) modification of the ribosomal binding site by chromosomal mutation, or
(3) production of esterase by Enterobacterales that hydrolyze macrolides.
How are macrolides and azalides absorbed?
Well-absorbed from the duodenum following oral administration
Minimal absorption occurs after topical or ophthalmic use.
How are macrolides and azalides distributed?
Distribute readily to body tissues and enter pleural fluid, ascitic fluid, middle-ear exudates, and sputum. When meninges are inflamed, macrolides enter the CSF.
How are macrolides and azalides metabolized?
Partially metabolized by the liver, and clarithromycin is converted to active metabolites
How are macrolides and azalides excreted?
Excreted mainly unchanged in bile; the drug is also excreted unchanged in urine in varying degrees
Why does erythromycin have so many drug interactions?
Erythromycin is heavily metabolized by CYP3A4, which explains many of its drug interactions.
Azithromycin needs to be given cautiously in which patients?
principally excreted via the liver. Patients with impaired hepatic function require cautious use of this drug
What EKG changes must be monitored for macrolides and azalides use?
QT interval
Erythromycin is contraindicated for patients with?
Preexisting liver disease
Clindamycin dosing is dependent on?
Renal impairment with CrCl less than 30 mL/min, with or without hepatic impairment, requires that dosages be halved or the dosing interval doubled.
Adverse reactions of macrolides and azalides
Dose-related GI symptoms. Liver abnormalities
Why do Clarithromycin and erythromycin have the most drug interactions?
because they are strong inhibitors of the CYP enzymes, particularly CYP3A4.
Clinical uses of erythromycin
Erythromycin ophthalmic ointment 0.5% is administered to all newborns to prevent ophthalmia neonatorum. Erythromycin is indicated in chlamydial conjunctivitis in newborns and chlamydial pneumonia in infants caused by C. trachomatis
What is a major reason for selection of azithromycin over other drugs ?
the enhanced compliance caused by its convenient dosing schedule. However, with its once-daily dosing and short duration of 3 to 5 days, a single missed dose could jeopardize the successful outcome.
