Macrolides exam 1 drug list Flashcards
Name 3 Macrolides:
Azithromycin
Erythromycin
Clarithromycin
Are macrolides Bactericidal or bacteriostatic?
Bacteriostatic
Prototype drug
Erythromycin
Azithromycin is derived from
Erythromycin
Due to drug interactions and side effects of Erythromycin and clarithromycin
Azithromycin is preferred and is the majority of macrolide use
Macrolides exhibit
Immunomodulating properties (useful in infectious diseases and cystic fibrosis)
Macrolide MOA
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.
Azithromycin Indications
Chronic bronchitis, sinusitis, CAP, Pharyngitis, and tonsillitis
Uncomplicated skin soft tissue infections
Chlamydia trachomatis and gonorrhea
Travelers diarrhea
Erythromycin Indications
CAP, bronchitis, pertussis
Impetigo cellulitis
Neonatal conjunctivitis caused by (N. gonorrhoeae or chlamydia trachomatis)
Chlamydia
Prophylaxis for rheumatic fever in those with penicillin allergies
Bacterial endocarditis for dental or surgical procedures
Clarithromycin Indications
CAP, bronchitis, sinusitis, pharyngitis
H. pylori eradication
acute otitis media
Dental procedures (endocarditis)
Macrolides absorption
Well-absorbed from the duodenum with oral administration
Minimal absorption from topical or ophthalmic use
Macrolide Distribution
Readily to body tissues
Enters pleural fluid, ascitic fluid, middle ear exudates, and sputum.
Meninges if they are inflamed
Enter CSF
Macrolide Metabolism
partially by the liver
Macrolide excretion
mainly unchanged in the bile, also unchanged in the urine
Both Erythromycin and Clarithromycin have a higher number of
drug interaction due to? What medication should be stopped if taking either abx?
being strong inhibitors of the CYP enzymes (CYP3A4)
HMG-CoA Reductase Inhibitors (Statins) should be stopped while on
either due to risk of severe myopathy or rhabdomyolysis
Erythromycin is heavily metabolized by
CYP3A4 which explains its many drug interactions
Erythromycin contraindicated in patients with?
Preexisting liver disease
Due to Azithromycin’s being excreted via the liver?
Patients with hepatic dysfunction require cautious use of the drug
What EKG change has been observed?
QT interval
Macrolide ADRs
Dose-related GI symptoms, including nausea, vomiting, abdominal pain, cramping, and diarrhea.
Azithromycin and erythromycin ADRs
Associated with liver abnormalities, including hepatitis, cholestatic jaundice, and hepatic failure.
What’s the major reason selecting azithromycin over other macrolides?
Enhanced compliance due to convenient once a day dosing for 3 to 5 days, missing one day could cause unsuccessful treatment.
Macrolide Resistance
(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.
Clindamycin MOA
Binds to 50S subunit of bacterial ribosome; Suppresses protein synthesis
Clindamycin indications
Limited due to potential for severe diarrhea/C-Diff, resistance, and better tolerated alternatives
Clindamycin active against
Gram positive bacteria
anaerobic pathogens
Clindamycin significant role in
Secondary infections due to staphylococcal/streptococcal species in penicillin-allergic patients
Clindamycin impact on septic shock?
Inhibition of protein synthesis, can decrease toxin production
Clindamycin resistant considerations
Ribosomal receptor site mutation/modification
Enzymatic inactivation
Clindamycin Absorption/Distribution
PO: Complete absorption, not affected by gastric acid or food
Distributes to pleural/peritoneal fluids w/high conc in bile/bone
Poor CSF penetration
Highly protein bound
Crosses placenta and found in breast milk
Clindamycin Metabolism/Excretion
Metabolism in liver
Excreted in bile/urine(10%)
No dosage modification unless severe renal/hepatic impairment
Clindamycin use in infants and children
Reserved for serious infections, When less toxic alternatives are inappropriate
Clindamycin ADRs
GI: N/V, Bitter metallic taste, Dizziness, Vertigo, H/a, hypotension, rare cardiac arrhythmias,
Indications of hepatic dysfunction
Risk for C-Diff very high
Drug interactions
Erythromycin: Antagonist effects
Kaolin-pectin: Delays GI absorption
NMB: Severe respiratory depression
Clindamycin clinical use
Bacterial Endocarditis prophy as alternative for penicillin allergic pt
Pneumococcal pneumonia, skin/tissue infections as penicillin alternative
Drug-Resistant Penumococcal Infections
