19 Macrolides, Ketolides, Tetracyclines Cupo Flashcards
What is the MOA of Macrolides?
Reversibly bind the 23S ribosomal RNA in the 50S-subunit of the bacterial ribosome. Interferes with peptide bond formation of the growing peptide chain. Thus, suppress RNA-dependent protein synthesis
What are the mechanisms of acquired resistance to Macrolides?
Target site alteration - encoded by erm A, B, C genes. Alteration in transport (efflux) - encoded by mrsA, mefA, mefE (confers cross-resistance to 14- and 15-membered rings, but not 16-membered
What are the Macrolides?
Erythromycin, Clarithromycin, Azithromycin
How is Erythromycin degraded?
Acid degradation. Erythromycin in acid rapidly converted to anhydroketal and spiroketal derivatives. Result: potent GI stimulatory effects
Which Macrolide required renal adjustment?
Clarithromycin, all others are primarily hepatically cleared
What is the distribution of Macrolides like?
Lipophilic. Extensive penetration to tissues/fluids. Respiratory tract concentrations > serum. Increased concentrations in macrophages, PMNs (highest azithro). Notable exception: not well penetrated to CSF
What is the metabolism/elimination of Erythromycin like?
Biliary excretion of unchanged drug
What is the metabolism/elimination of Calrithromycin like?
Metabolized to 7 metabolites, major active = 14-OH; (renal adjust for CrCl < 30)
What is the metabolism/elimination of Azithromycin like?
Biliary excretion of unchanged drug
What are the Macrolide pharmacodynamics?
Bacteriostatic. Time-dependent. PAE - variable: 2-3 hours
What is the Spectrum of Activity for Erythromycin?
MSSA, S. pyogenes, S. pneumoniae (Pen-S). Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Bordetella pertussis. NOT Enterococci, NOT MRSA
What are the clinical applications of Erythromycin?
āMotilin effectā (GI stimulatory) - 240mg IVPB Q8h. Diabetic gastroparesis. Post-op ileus
What are the ADRs associated with Erythromycin?
N/V/D (main). Abdominal discomfort. Urticaria, rash. Ototoxicity. Increased LFTs. Cholestatic jaundice (esp. estolate). Arrhythmias
What is the structure of Clarithromycin like?
14-membered lactone ring. Replace hydroxyl group at C6 position with methoxyl group (enhanced spectrum of activity, acid stability; may take without regard to meals, decreased GI ADRs, longer t1/2, easier dose and administration
What is the Spectrum of Activity for Clarithromycin?
Gram-positive. Atypicals. Notable additions: H. influenzae (d/t addition effect of 14-OH Clarithro), H. pylori, Mycobacterium avium complex (MAC)
What are the dosage formulations for Clarithromycin?
Available PO only. Biaxim 250mg, 500mg tablets. Biaxin XL 1000mg QD. Prevpac - with Amox 500mg, Prevacid 30mg
What are the clinical applications of Clarithromycin?
ABECB: 250-500mg PO x 7-14 days. H. pylori: (part of triple regimen) x 10-14 days: clarithro, lanso, amox. MAC prophylaxis: 500mg po BID. Sinusitis: 500mg BID x 14 days. Pharyngitis: 250mg BID x 10 days
What are the ADRs associated with Clarithromycin?
Taste perversion (metallic, very common). N/V/D (less than Ery). Dyspepsia. Abdominal pain, Flatulence. HA
What is the structure of Azithromycin like?
15 membered ring. N-methyl group inserted between C9 and C10
What is the Spectrum of Activity for Azithromycin?
Gram (+). Atypicals, M. catarrhalis, H. influenzae. Additionally: N. gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum
What are the dosage formulations of Azithromycin?
Oral: 250, 500, or 600mg. IV: 500mg. Z-pak: 500mg x 1, 250mg x 4 days. Zithromax Tri-Pak: 500mg QD x 3 days. Zithromax powder (oral suspension): 100 and 200mg/5ml. Zmax ER Powder: 2g/60ml
What are the clinical applications of Azithromycin?
CAP guidelines: 500mg PO/IV + B-lactam. Mild-Moderate ABECB: 500mg daily x 3 or 500mg x 1, 250mg QD x 4. Sinusitis: 500mg PO QD x 3. Gonorrhea: 2g PO x 1. Chlamydia infection: 1g PO x 1. MAC prophylaxis: 1,200mg Qweek
What are the ADRs associated with Azithromycin?
D/V. Abdominal pain. Vomiting (much lower than others)
What unique effects do Macrolides have?
Immunomodulatory effects: maintenance of epithelial barrier. Effects on neutrophils (accumulation and migration, reduce reactive oxygen species). Modification of cytokine production. Suppress bacterial quorum sensing. Mucoregulatory and ciliary effects. Effects on biofilm and decrease bacterial adherence. Macrolides are commonly used in CF for these reasons
What is the DDI between Macrolides and Rifampin like?
Decreased levels of Erythro, Clarithro
What is the caution of Macrolide DDIs causing QT prolongation?
Increased chance when used with Quinidine, Amiodarone, or Sotalol
What pregnancy category are Macrolides?
Pregnancy Category B
What is some Patient Counseling for Macrolides?
Skin rash, hives, itching or difficulty breathing, swelling of the face, throat, lips: contact healthcare professional. For Erythromycin Estolate (Ilosone): severe stomach pain, weakness, or if the skin has a yellow color. Fast or irregular heartbeat (Ery, Clar). Taste disturbances (Clar)
What is Telithromycin (Ketek)?
First in class. Designed to treat macrolide-resistant respiratory tract pathogens
What is the Spectrum of Activity for Telithromycin?
S. aureus, S. pneumoniae (DRSP), H. influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae