PRO synthesis inhibitors Flashcards
glycylglycine agents
MOA
tigecycline
- similar to tetracyclines, but binds with higher affinity; bacteriostatic agent against hershey isolate of MRSA
- effective against strains that are tetra resistant
aminoglycosides
MOA
-gentamicin, streptomycin
MOA: bind irreversibly to the 30S ribosomal subunit and inhibit PRO synthesis at several levels
-bactericidal
-concentration dependent killing with significant PAE
[-blocks initiation of PRO synth, terminates translation, misincorporation of AA –> generation of altered PRO]
aminioglycosides spectrum & resistance
- gentamicin, streptomycin
- primarily aerobic gram - rods, **combination therapy with PCN or vanco acts synergistically and extends coverage to gram + pathogens (cell wall disturbing agent allows better penetration of aminoglycosides)
resistance: mutatnt bacterial ribosome - decreased uptake or efflux
- enzymatic inactivation of drug**
aminoglycosides PK
- gentamicin, streptomycin
- absorption: highly polar, poorly absorbed from GI tract; given IV or IM
- not well distributed to most cells, eye or CNS
- high concentrations only in inner ear and renal cortex –> toxicity**
- renally cleared
aminoglycosides SE
- ototoxitiy: irreversible loss of hearing**
- vestibular toxicity (permenant)
- reversible renal toxicity
specifics to know re: streptomycin & use
- high resistance limiting use**
- mycobacterial infections (TB)
- pregnancy: deafness in newborns **
specifics to know and uses re: gentamicin
- resistance = poor drug uptake
- *main use severe gram - infections and for others with PCN/vanc
- topical for burns, wounds, skin lesions
- *ototoxicity, mainly vestibular and irreversible
macrolide antibiotics
azithromycin
clarithromycin
erythromycin
macrolide antibiotics MOA
**bind reversibly to 50S subunit
-block tRNA peptide movement from A to P site
-bc of the proximity to site of action, macrolides competitively inhibit ribosome binding of streptogramins, clindamycin, chloramphenicol **
bacteriostatic **
macrolide antibiotics spectrum
- narrow but somewhat broader than PCN
- accumulate to a far greater extent in gram + bacteria b/c of difficulty penetrating outer membrane of gram neg
- *clarithromycin and azithromycin are more effective than erythromycin against anaerobes
macrolides resistance
develops rapidly
-cross-resistance w/in class
3 mechanisms
-efflux pump
-methylase modifies the bacterial ribosome so unable to bind drug [MLS type B]
-hydrolysis of macrolides by esterases produced by enterobacteriacaea
macrolides PK
- erythromycine is unstable in acidic environement, salts and esters or EC tabs for use orally
- other macrolides are more acid stable
- poor penetration of CNS
- *erythromycin penetrates into abscesses
clinical use of macrolides
- *alternative to PCN esp for allergy
- *prophylaxis against bacterial endocarditis in PCN allergy
- *oral facial infections for periapical ascessis, azythromycin is as effective as amoxicillin/clavulanate
- resp infections from atypical microbes
- common bacterial infections but resistance develops rapidly
macrolides adverse effects
- *GI/motility disturbances
- *hepatotoxicity - cholestatic hepatitis, greater with erythromycin estolate; reversible
**erythromycin and clarithromycin inhibit CYP3A4 potentiates effects of (theophylline, warfarin, carbamazepine, astemizole, protease inhibitors)
ketolide
telithromycin
-1st member of new drug class
modified version of erithromycin w increased acid stability, affinity for bacterial 50S ribosome, and reduced induction of bacterial resistance [no MLS B]
