Inhibition of the 50S subunit Flashcards
1
Q
macrolides
A
- erythromycin
- clarithromycin
- azithromycin
2
Q
lincosamides
A
- clindamycin
3
Q
streptogramins
A
- quinupristin
- dalfopristin
4
Q
oxalidones
A
- Linezolid
- tedizolid
5
Q
- protein synthesis inhibitors that “buy” aka bind, to the 30S subunit
A
- aminoglycosides
- tetracyclines
6
Q
- protein synthesis inhibitor that “sells” at th50S ribosomes
A
- Streptogarmins
- Erythromycin
- lincosamides
- Linezolide
7
Q
- broad spectrum protein synthesis inhibitors spectrum coverage
A
- Macrolides (50s)
- Chloramphenicol (50s)
- Tetracyclines (30s)
8
Q
- narrow spectrum protein synthesis inhibitors coverage
A
- aminoglycosides (30s) (-)
- lincosamide/clindamycin (50s) (+)
- streptogarmins (50s) (+)
- oxazolidones/linezolid (50s) (+)
9
Q
- biochem and catalysis subunit of protein
A
50S
10
Q
- recognition and binding subunit protein
A
30S
11
Q
- core structure coantains a 14-membered or 15-membered lactone ring (cyclic ester) as well as 2 sugar units
A
macrolides
12
Q
- how does clarithromycin differ from erythromycin?
A
- methylation of one OH group
13
Q
- how does Azihtromycin differ from other macrolides?
A
- removal of upper ketone group and addition of a methyl substituted nitrogen into the lactone ring
14
Q
- Macrolide unstable in acidic pH due to acid-catalyzed intramolecular cyclization involving the C6 OH and the C9 ketone leading to anhydroerythromycin (GI irritant)
A
erythromycin
15
Q
- why do clarithromycin and azithromycin have better acid stability?
A
- structural modification of C60H group and ketone group
these modifications improve penetration into host cells, increase passage via porins and generally broaden the spectrum of aactivity
16
Q
- act by blocking tunnel pore by which growing peptides exit ribosome by binding to proximal part of the exit tunnel
- backlog develops near P site and then extends to A site
- bottom line, they inhibit A and P sight functions
- Do NOT directly block peptidyl transferase activity, peptide bond can still be formed!!!
A
- Macrolides
17
Q
- macrolide with higher activity against intracellular pathogens such as Chlamydia, Legionella, Moraxella, species and Helicobacter pylori compared to erythromycin
A
Clarithromycin
18
Q
- macrolide, with the best activity against respiratory infections such as H. Influenzae and Moraxella catarrhalis, S. pnuemoniae
A
Azithromycin
19
Q
preferred therapeutics for chlamydial infections
A
- Azithromycin
- Doxycycline
20
Q
used to eliminate corynebacterium diphtheria
A
- Erythromycin or penicillin
21
Q
used against legionellosis
A
- fluroquinolones or azithromycin
22
Q
used against mycoplasma pneumonia aka atypicals
A
- azithromycin or Doxycycline
23
Q
used against mycobacterium avium
- MAC infections
A
- azithromycin in combo w rifampin and ethambutol
24
Q
macrolides are highly active against….
A
- CAP
- STD
- H. species
25
Q
what do macrolides treat?
***think CALM
A
- Campylobacter
- Atypical
- Legionella
- Moraxella
26
Q
- macrolide, only oral doses in the US
- can take w food
- eliminated by both renal and hepatic mechanisms
- half life of 3-8 hours
- CYP 3A4 inhibition
A
Clarithromycin
27
Q
- macrolide used for once daily dosing oral and IV formulations
- tissue concentration exceeds serum concentration by 10 to 100 fold, large Vd
- eliminated mainly by hepatic systems and minimal CYP 3A4
A
Azithromycin
28
Q
Adverse rxns of macrolides
- think TACO
A
- Torsade
- Allergy
- Cramp
- Ototoxicity
29
Q
- structure is 5 membered heterocyclic nitrogen containing ring joined via an amide link to a sugar reside
- binds 50S residue to inhibit protein synthesis
- overlaps macrolide binding site
- affects A to P translocation secondarily via backlog that develops
A
- LIncosamide…aka Clindamycin
30
Q
- clindaymycin good coverage
- think CAP
A
- Cocci
- Amaerobes
- Parasites
31
Q
- no coverage of clindamycin
- think CENA
A
- C. diff
- Enterococci
- Negative gram aerobes
- Atypicals
32
Q
- clindamycin metabolism
A
liver, no renal dose adjustments
33
Q
- streptogarmins coverage
- think MME
A
- gram positives
- MRSA/MSSA
- VRE
34
Q
- IV admin
- 1 hours half life
- P450 inhihition of 3A4
A
streptogarmins
35
Q
- true inhibitor of peptide bond formation
- very dangerous side effects, covers gram negs, pos, anaerobes and atypicals
- inhibited by hepatic metab, so no good for liver issues
- bone marrow toxicity
- grey baby syndrome
A
chlorophenicols
36
Q
- interfere w formation of the 70S fet-tRNA initiation complex
- no cross resistance w other drugs
- oral or IV
- wide distribution including CSF
- 4-6 hr half life
- caution in hepatic diseases, doesn’t effect renal issues
- weak inhibitor of MAO
A
- Oxazolidones (Linezolidones) (Tedizolid)
37
Q
Oxazolidones coverage
A
- Aerobic gram pos
- Staphylococci
- Enterococci
- Streptococci
- NOT used clically against aerobic gram neg bacteria
38
Q
side effects of Linezolid
A
- serotonin syndrome
- cheese reaction
39
Q
difference in streptogarmins vs. linezolid
A
- streptogarmins only covers E. Faecium including VRE faecium but NOT E. faecalis, linezolid covers both
40
Q
50S inhibitor MRSA coverage
A
- Clindamycin
- Streptogarmins
- Linezolid
41
Q
- only 2 50S inhibitors NOT metabolized only by the liver
A
- Linezolid
- Clarithromycin
42
Q
- A to P translocation/ejection of already formed peptide
- block peptide exit tunnel at 50S ribosome
A
- macrolides
- clindamycin
43
Q
- peptide chain elongation
- amino acid incorporation
- block amino acyl tRNA to A site
A
- streptogarmins (50S)
- tetracyclines (30S)
44
Q
- formation of initiation complex
- interfering w the formation of 70S fMet-tRNA initiation complex
A
- Linezolid (50S)
45
Q
- peptide bond formation
- inhibit peptidyl transferace
A
- chloramphenicol (50S)
46
Q
trple effect
- initiation, premature termination and incorporationof incorrect amino acid
A
- aminoglycosides (30S)
