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IOS 10 Exam 2

Macrolides & ketolides

MOA of macrolides is Reversible binding of the 50S subunit of domain V thus inhibiton of translation (same as clindamycin and chloramphemicol)
MOA of ketolides Reversible binding to Domain V and Domain II of 50 S subunit of ribosome thus blocking translation
Macrolides are considered what type of killing Bacterostatic for many but for S. pyrogenes (group A) and S. pneumoniae they are bacteriocidal.
Resistance of macrolides Permibility (gram-), enzymatic inactivation, efflux, single alterations in 23S subunit of 50S decreased binding, methylation of 23S subunit of 50S caused alteration o binding
Resistance of ketolide Scarce, alteration in telithromycin binding site via chromosomal or plasmid mutations
Erythromycin ADME inactivated byy gastric acids requires capsulation, distribution into all tissues (not CNS), metabolism via p450, elimination fecal
Clarithromycin ADME Good stability, extensive distribution,active metabolite
Azrithromycin ADME Acid stable, reduced with food. Hepatic metaoblism, Elimination may require weeks!!!
Gram + aerobe activity of macrolides Good,: staph, strep (poor-MRSA, enterococci)
Gram- aerobic activity of macrolides Moderate: neisseria gonorrhowae, M. catarrhalis, H. inf, Some activity against enterobacteriaw (shigellam campylobacter, vibrio)
Anaerobic acitivty of macrolides Little
Atypical activity of macrolides DRUGS OF CHOICE
Other microbes macrolides cover Borrelia burgdorferi, mycobacterium, H. pylori
Macrolide side effects GI (N/V, DIa), thrombophlebitis, ALL, hepatotoxic, ototoxic, superinfection, torsades de points, pseudomembraneous colitis
Erythromycin DI buspirone, carbamazepines, clomiramine respiradone, clozapine, cyclosporin, digoxin, felodpine, lovastatin, methylprednisolone, midazolam, phenytion, tacrolimus, theophylline,valproate, warfarin
Claithromycin DI carbamazepine, cyclosporin, digoxin, rifampin, rifabutin, ritnoravie, zidovudine
Azithromycin DI Cyclosporin
Ketolides ADME moderate abs, VD moderare 2.9L, T1/2 10 hours, metabolism is Cp450 inhibition (huge), with 80%various elimination methods
Ketolide spectrum of activity: Respiratory tract, S. pneumonia, pyrogenes, agalactiaw, H. infl, M. catarrhalis, C. pneumoniaw, L. pneumoniaw, M. pneumoniae, B. pertussis, MSSA
Ketolide SE GI most common, hepatotoxcity, ocular rate
Ketolide DI Simvastatin and lovastatin can cause increase in statin and decrease AB. Rifampin causes autoinduction of self and ketolides
Created by: liza001



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