antibacterial drugs targeting protein synthesis Flashcards
what is mupirocin
a pre-ribosomal inhibitor. isoleucyl tRNA synthetase inhibitor
name some ribosomal inhibitors
oxazolidinones, tetracyclines, aminoglycosides, chloramphenicol, macrolides
name a indirect ribosomal inhibitor
fusidic acid
what is the basis of selective toxicity for mupirocin
there is a structural difference between eukaryotic and prokaryotic isoleucyl-tRNA synthetase
what is the basis of selective toxicity for fusidic acid and tetracycline
there is a difference in uptake into eukaryotic and prokaryotic cells
what is the mode of action of mupirocin
it is bacteriostatic. acts as a substrate analogue to inhibit isoleucyl tRNA synthetase.
what is the clinical use of mupirocin
gram negative restricts its access making it have a narrow spectrum. ointment for staphylococcal and streptococcal skin infections. eliminates nasal carriage of MRSA . it is not applied systematically because it is de esterified in kidney and liver and produces metabolites that have no antibiotic activity.
which drugs target the 50s unit
aminoglycosides, chloramphenicol, lincosamides, macrolides, oxazolidinones, streptogramins
what drugs target the 30s unit
aminoglycosides, tetracyclines
what are oxazolidinones and name some of them
fully synthetic class, bacteriostatic, only target gram positive, bind on 50s. linezolid and tedizolid
what is the mode of action of oxazolidinones
the drug interferes with binding or the correct positioning of initiator tRNA in ribosomal P site
what is the clinical use of oxzolidinones
oral agents, has side effects such as skin reactions, mild abnormalities of liver function, reversible thrombocytopenia and anaemia.
what are tetracylcines
semi synthetic, broad spectrum, lipophillic members more active than hydrophillic, bind to A site in 30s unit. prevent association with aminoacyl-tRNA with ribosome.
what is the clinical use of tetracyclines
moslty oral, and IV, for skin, soft tissue and intra abdominal infections.
what are some side effects of tetracylcines
gastrointestinal disturbance, photosensitivity, CNS effects, deposition in developing bones and teeth.
what are aminoglycosides
naturally occurring,
what is the mode of action of aminoglycoside
bactericidal, bind to 30s unit via 16s or can also bind 50s. inhibits ribosomal translocation when peptidyl tRNA moves from A to P site. inhibits translation proof reading.
describe aminoglycoside mediated killing
1) reduces translational fidelity
2) abnormal proteins with external hydrophobic patches produced
3) proteins escape and fold in membrane
4) membrane integrity compromised leads to cell death
what is the clinical use aminoglycosides
mostly used IV, when alone used for severe sepsis, plague, tularaemia, enterococcal endocarditis
when in combination used for, gram positive and anaerobic infections and TB
what are side effects of aminoglycosides
toxicity which is mechanism based, impaired hearing and balance functions of inner ear, nephrotoxicity, neuromuscular blockade.
what is chloramphenicol
broad spectrum, binds to 50s unit at PTC. blocks aa-tRNA binding. naturally occurring.
given orally, IV, topical
what are side effects of chloramphenicol
myelosuppression, gray syndrome the toxicity restricts clinical use.
still used to treat typhoid and paratyphoid fever
what are macrolides
natural, have a macrocyclic lactone ring, produced by streptomyces
what is azithromycin
a type of macrolide, called azalide, has great coverage of gram negative
what is the mode of action of macrolides
bind to 23s rRNA at peptide exit in 50s unti. block exit of peptide causes premature dissociation of peptidyl-tRNA form P site
how are macrolides used clinically and what are its side effects
used orally or IV, erythromycin is acid labile because of gastric degradation after taken orally.
side effects include gastrointestinal disturbance, jaundice, ototoxicity.
what is fusidic acid
it is a natural steroid like antibiotic
what is the mode of action of fusidic acid
interferes with release of elongation factor G from the ribosome
what is the clinical use of FA
limited to gram positive organisms, applied topical, oral or IV therapy, usually in combination to suppress emergence of point mutations in EF-G conferring resistance
what are some side effects of FA
rashes, jaundice
