Bacterial Protein Synthesis Inhibitors Flashcards
Tobramycin
Aminoglycoside
MOA: inhibit translation by binding to 16S rRNA of 30s ribosomal subunit causing misreading and leading to cell death
Gentamicin
Aminoglycoside
MOA: inhibit translation by binding to 16S rRNA of 30s ribosomal subunit causing misreading and leading to cell death
Amikacin
Aminoglycoside
MOA: inhibit translation by binding to 16S rRNA of 30s ribosomal subunit causing misreading and leading to cell death
Best against pseudomonas
General aminoglycosides characteristics, spectrum of use , side effects
Bactericidal
Concentration dependent
Very low bioavailability
Renal eliminated
Sub- optimal penetration of sputum/lung, bone, CNS, abscesses
Excellent against enterobacteraciae, acinetobacter, pseudomonas, other gnr
+ cell wall active agent has good activity vs many GPC
SE: Nephrotoxicity, ototoxity
Amino glycosides main uses and resistance is from what
Uses: Gram- nosocomial Infections Mycobacterial infections ( Amikacin, streptomycin) Pseudomonal infections Gram + synergy in endocarditis
Resistance
Enzymatic inactivation ( enterobacteraciae)
Altered membrane permeability ( pseudomonas)
Target site mutation
Clindamycin
Lincosamides
Moa: inhibits translation by binding the 50s subunit of bacterial ribosomes. -> inhibits peptidyl transferase
Basteriostatic
90% bioavailable
Lincosamides general characteristics
Anaerobes, but C. difficile
Staphylococci ( including some MRSA) streptococci, anaerobes
- not good for MRSA pneumonia or atypicals
Se:pseudo membranous colitis
Uses: aspiration pneumonia, SSTIs, anaerobic infections, (topical )acne
Resistance is due to altered target site
- in gram positives , often cross- resistant with macro lodes, streptogramins.
Erythromycin
Macrolide
MOA: inhibit translation by binding 23s rRNA of 50s subunit of ribosome
Bacteriostatic
Clarithromycin
Macrolide
MOA: inhibit translation by binding 23s rRNA of 50s subunit of ribosome
Bacteriostatic
H. Pylori
More convenient dosing than erythromycin
Azithromycin
Macrolide
MOA: inhibit translation by binding 23s rRNA of 50s subunit of ribosome
Bacteriostatic
More convenient dosing than erythromycin
Macrolides general characteristics
Achieve high intracellualr concentrations
Highly bioavailable
Excellent lung penetration , poor CNS
Hepatic metabolism or biliary excretion
Uses: streptocussous spp, atypical pathogens, h. Influenza, m. Catarrhalis
Macrolides adverse effects
GI disturbances , rash
Drug interactions
Erythro and clarithro inhibit CYP 1A2, 3A3/4
Azithro lower interaction potential
Main use of Macrolides and resistance to Macrolides
Uses Cap URTIs MAC PUD clarithro Promotility ( erythromycin )
Resistance
Efflux pump, altered target site
Telithromycin
Ketolide Microlide analogue with increased s. Pneumoniae activity Po only Addition ae : hepatotoxicity Main use - CAP
Minocycline
Tetracycline
MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex
Bacteriostatic
Tetracycline
Tetracycline
MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex
Bacteriostatic
Doxycycline
Tetracycline
MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex
Bacteriostatic
Doxycycline
Tetracycline
MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex
Bacteriostatic
Tetracyclines characteristics , adverse effects and drug interactions
Concentration independent Highly bioavailable Poor CNS penetration Spectrum - atypicals - some gnr and GPC, limited by resistance - bacillus anthracis, b. Burgdorferi , y. Pestis, t. Pallidium, h. Pylori. - some MRSA
Adverse effects
- tooth discoloration
- GI upset- n/v, borborygmous
- photosensitivity
Tetracyclines - main uses and resistance
Acne, CAP (doxycycline) , tick-borne diseases, PUD, STDs
- demeclocycline’s only use is SIADH
Resistance due to efflux pump
Tigecycline
Glycycyline
Modified tetracycline that has an expanded spectrum Very large vd Hepatic elimination Covers many gnr and GPC - includes vre and MRSA Good anaerobic - not c. Difficile Not pseudomonas or. Proteus
Ae - significant n/v
Use: SSTIs, intra-abdominal infections
Not good enough for HAP
Chloramphenicol
MOA: binds to 23s rRNA of 50s subunit inhibiting protein synthesis by blocking peptidyl transferase
Bacteriostatic
Highly bioavailable
PO= IV dosing
Chloramphenicol characteristics
Good CNS penetration
Hepatic all metabolized through conjugation
Useful spectrum
- streptococci, staphylococci ( Methicillin sensitive only), enterococci including VRE
-anaerobes
- some GNR
Chloramphenicol adverse effects and drug interactions
Adverse effects
- gray baby syndrome - d/t neonatal impairment of. Conjugation
Vomiting , flaccidity, gray color,response distress, met acidosis
- bone marrow suppression. - reversible - dose related , irreversible
idiopathic
Drug interactions:
Increased levels of phenytoin, phenobarbital, warfarin
Used: not in USA, vre infections
Resistance : enzymatic inactivation
