antibacterial drugs targeting protein synthesis

Question 1

what is mupirocin

Answer 1

a pre-ribosomal inhibitor. isoleucyl tRNA synthetase inhibitor

Question 2

name some ribosomal inhibitors

Answer 2

oxazolidinones, tetracyclines, aminoglycosides, chloramphenicol, macrolides

Question 3

name a indirect ribosomal inhibitor

Answer 3

fusidic acid

Question 4

what is the basis of selective toxicity for mupirocin

Answer 4

there is a structural difference between eukaryotic and prokaryotic isoleucyl-tRNA synthetase

Question 5

what is the basis of selective toxicity for fusidic acid and tetracycline

Answer 5

there is a difference in uptake into eukaryotic and prokaryotic cells

Question 6

what is the mode of action of mupirocin

Answer 6

it is bacteriostatic. acts as a substrate analogue to inhibit isoleucyl tRNA synthetase.

Question 7

what is the clinical use of mupirocin

Answer 7

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.

Question 8

which drugs target the 50s unit

Answer 8

aminoglycosides, chloramphenicol, lincosamides, macrolides, oxazolidinones, streptogramins

Question 9

what drugs target the 30s unit

Answer 9

aminoglycosides, tetracyclines

Question 10

what are oxazolidinones and name some of them

Answer 10

fully synthetic class, bacteriostatic, only target gram positive, bind on 50s. linezolid and tedizolid

Question 11

what is the mode of action of oxazolidinones

Answer 11

the drug interferes with binding or the correct positioning of initiator tRNA in ribosomal P site

Question 12

what is the clinical use of oxzolidinones

Answer 12

oral agents, has side effects such as skin reactions, mild abnormalities of liver function, reversible thrombocytopenia and anaemia.

Question 13

what are tetracylcines

Answer 13

semi synthetic, broad spectrum, lipophillic members more active than hydrophillic, bind to A site in 30s unit. prevent association with aminoacyl-tRNA with ribosome.

Question 14

what is the clinical use of tetracyclines

Answer 14

moslty oral, and IV, for skin, soft tissue and intra abdominal infections.

Question 15

what are some side effects of tetracylcines

Answer 15

gastrointestinal disturbance, photosensitivity, CNS effects, deposition in developing bones and teeth.

Question 16

what are aminoglycosides

Answer 16

naturally occurring,

Question 17

what is the mode of action of aminoglycoside

Answer 17

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.

Question 18

describe aminoglycoside mediated killing

Answer 18

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

Question 19

what is the clinical use aminoglycosides

Answer 19

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

Question 20

what are side effects of aminoglycosides

Answer 20

toxicity which is mechanism based, impaired hearing and balance functions of inner ear, nephrotoxicity, neuromuscular blockade.

Question 21

what is chloramphenicol

Answer 21

broad spectrum, binds to 50s unit at PTC. blocks aa-tRNA binding. naturally occurring.
given orally, IV, topical

Question 22

what are side effects of chloramphenicol

Answer 22

myelosuppression, gray syndrome the toxicity restricts clinical use.
still used to treat typhoid and paratyphoid fever

Question 23

what are macrolides

Answer 23

natural, have a macrocyclic lactone ring, produced by streptomyces

Question 24

what is azithromycin

Answer 24

a type of macrolide, called azalide, has great coverage of gram negative

Question 25

what is the mode of action of macrolides

Answer 25

bind to 23s rRNA at peptide exit in 50s unti. block exit of peptide causes premature dissociation of peptidyl-tRNA form P site

Question 26

how are macrolides used clinically and what are its side effects

Answer 26

used orally or IV, erythromycin is acid labile because of gastric degradation after taken orally.
side effects include gastrointestinal disturbance, jaundice, ototoxicity.

Question 27

what is fusidic acid

Answer 27

it is a natural steroid like antibiotic

Question 28

what is the mode of action of fusidic acid

Answer 28

interferes with release of elongation factor G from the ribosome

Question 29

what is the clinical use of FA

Answer 29

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

Question 30

what are some side effects of FA

Answer 30

rashes, jaundice