L6 - Antibacterials : protein synthesis

Question 1

What is a pre-ribosomal stage inhibitor?

Answer 1

mupirocin: isoleucyl tRNA synthetase inhibitor

Question 2

What are ribosomal inhibitors?

Answer 2

oxazolidinones
tetracyclines
aminoglycosides
chloramphenicol
macrolides

Question 3

What is an indirect ribosomal inhibitor?

Answer 3

fusidic acid

Question 4

What are the 3 stages of protein synthesis?

Answer 4

initiation
elongation
termination

Question 5

What are the 3 sites within the ribosome?

Answer 5

A-site
P-site
E-site

Question 6

What are generalised feature of antibacterial drugs targeting protein synthesis?

Answer 6

act on ribosome

bacteriostatic

Question 7

What are things that allow for selective toxicity?

Answer 7

difference between 70S and 80S ribosomes

Question 8

How is Mupirocin selectively toxic?

Answer 8

structural diff between prok and euk isoleucyl-tRNA synthetases

Question 9

How is fusidic acid and tetracycline selectively toxic?

Answer 9

different uptake in eukaryotic and prokaryotic cells

Question 10

What is the main side effect of ribosomal inhibitors?

Answer 10

inhibition of mitochondrial protein synthesis - similar to bacterial

endosymbiotic theory!

Question 11

How does mupirocin work?

Answer 11

substrate analogue to inhibit isoleucyl tRNA synthetase

Question 12

What is the role of isoleucyl tRNA sythetase?

Answer 12

amino acids are linked to a tRNA adaptor

specific aminoacyl-tRNA synthetase responsible for joining the 2 components

Question 13

What is the clinical use of mupirocin?

Answer 13

NARROW - cannot infect gram neg due do the outer membrane

treats staph and strep skin infections

eliminate nasal MRSA

Question 14

Why is mupirocin not applied systemically?

Answer 14

it would be rapidly de-esterified in kidney & liver

Question 15

What are the 2 oxazolidinones?

Answer 15

Linezolid

Tedizolid

Question 16

Facts about oxazolidinones?

Answer 16

bacteriostatic
Gram +ve only
bind on 50S ribosomal subunit

Question 17

How do oxazolidinones work?

Answer 17

LZD interferes with binding/correct positioning of the initiator tRNA in the p-site during the initiation process

Question 18

What are the clinical uses of oxazolidinones?

Answer 18

pneumonia

skin/soft tissue infections

Question 19

What are the side effects of LZD?

Answer 19

skin

gastrointestinal disturbance

liver function abnormalities

thrombocytopenia
anaemia

Question 20

How is TZD better than LZD?

Answer 20

reduced myelosuppression

increased antibacterial potency = SHORTER COURSE OF TREATMENT = LESS SIDE EFFECTS

Question 21

What are tetracyclines?

Answer 21

broad-spectrum action

bind to A-site within 30S subunit

Question 22

How do tetracyclines work?

Answer 22

prevent association of aminoacyl-tRNA with the ribosome

Question 23

What is the 3rd generation tetracycline?

Answer 23

Tigecycline

Question 24

How is tigecycline applied?

Answer 24

IV ONLY for skin. soft tissues & abdominal infections

Question 25

What are adverse effects of tetracyclines?

Answer 25

gastrointestinal disturbances photosensitivity CNS effects deposition in bones/teeth

Question 26

What is one of the only bactericidal drugs?

Answer 26

Aminoglycosides

Question 27

How do aminoglycosides work?

Answer 27

bind to 30S subunit via 16S rRNA OR bind BOTH 30S and 50S subunits

Question 28

What do aminoglycosides inhibit?

Answer 28

ribosomal translocation - peptidyl-tRNA moves from A to P site cause MIS-READING OF mRNA = abnormal proteins

Question 29

What does aminoglycoside look for?

Answer 29

watson-crick base pairing between codon and anti-codon reduces translation fidelity

Question 30

How does aminoglycoside actually kill cells?

Answer 30

Non-functional proteins increased number of external hydrophobic patches escape environment by burying in membrane - disruption and leakage

Question 31

What are aminoglycosides used for?

Answer 31

sepsis plague enterococcal endocarditis combination therapy for TB and Gram-pos infections

Question 32

What are adverse side effects of aminoglycosides?

Answer 32

ototoxicity nephrotoxicity neuromuscular blockade

Question 33

What is chloramphenicol?

Answer 33

true broad-spectrum treats typhoid & paratyphoid fever

Question 34

How does chloramphenicol work?

Answer 34

binds to 50S subunit at PTC - covers the a-site blocks aa-tRNA binding

Question 35

What are adverse side effects of chloramphenicol?

Answer 35

myelosuppression Gray syndrome

Question 36

What are Macrolides?

Answer 36

macrocyclic lactone ring with AMINO SUGAR and another sugar attached

Question 37

What is one of the worlds' best-selling antibacterial agents?

Answer 37

azithromycin

Question 38

How is azithromycin better than eryhtromycin?

Answer 38

greater coverage for gram neg respiratory tract pathogens

Question 39

What is the mode of action of macrolides?

Answer 39

bind to 23S rRNA at peptide exit site - 50S subunit block exit premature dissociation of peptidyl-tRNA from P-site

Question 40

How can macrolides be administered?

Answer 40

Oral | IV

Question 41

What are adverse side effects of macrolides?

Answer 41

gastrointestinal disturbances jaundice ototoxicity

Question 42

Why is oral administration not always good for macrolides?

Answer 42

erythromycin - acid labile gastric degradation

Question 43

What is the mode of action of fusidic acid?

Answer 43

interferes with release of elongation factor G from ribosome locks onto ribosome stops EFG from conformational change that would have led to dissociation

Question 44

What are clinical uses of FA?

Answer 44

limited to gram pos topical, oral, IV

Question 45

What are adverse side effects of FA?

Answer 45

rashes | jaundice

Question 46

How can protein synthesis inhibitors be used as adjunctive therapy?

Answer 46

REDUCE TOXIN PRODUCTION TOXINS PRODUCED BY BACTERIA = SYMPTOMS