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Flashcards in Bacterial Protein Synthesis Inhibitors Deck (32):
0

Gentamicin

Aminoglycoside

MOA: inhibit translation by binding to 16S rRNA of 30s ribosomal subunit causing misreading and leading to cell death

1

Tobramycin

Aminoglycoside

MOA: inhibit translation by binding to 16S rRNA of 30s ribosomal subunit causing misreading and leading to cell death

2

Amikacin

Aminoglycoside

MOA: inhibit translation by binding to 16S rRNA of 30s ribosomal subunit causing misreading and leading to cell death

Best against pseudomonas

3

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

4

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

5

Clindamycin

Lincosamides

Moa: inhibits translation by binding the 50s subunit of bacterial ribosomes. -> inhibits peptidyl transferase
Basteriostatic
90% bioavailable

6

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.

7

Erythromycin

Macrolide

MOA: inhibit translation by binding 23s rRNA of 50s subunit of ribosome

Bacteriostatic

8

Clarithromycin

Macrolide

MOA: inhibit translation by binding 23s rRNA of 50s subunit of ribosome

Bacteriostatic

H. Pylori
More convenient dosing than erythromycin

9

Azithromycin

Macrolide

MOA: inhibit translation by binding 23s rRNA of 50s subunit of ribosome

Bacteriostatic
More convenient dosing than erythromycin

10

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

11

Macrolides adverse effects

GI disturbances , rash

Drug interactions
Erythro and clarithro inhibit CYP 1A2, 3A3/4

Azithro lower interaction potential

12

Main use of Macrolides and resistance to Macrolides

Uses
Cap
URTIs
MAC
PUD clarithro
Promotility ( erythromycin )

Resistance
Efflux pump, altered target site

13

Telithromycin

Ketolide
Microlide analogue with increased s. Pneumoniae activity
Po only
Addition ae : hepatotoxicity
Main use - CAP

14

Minocycline

Tetracycline

MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex

Bacteriostatic

15

Tetracycline

Tetracycline

MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex

Bacteriostatic

16

Doxycycline

Tetracycline

MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex

Bacteriostatic

17

Doxycycline

Tetracycline

MOA : inhibit translation by binding reversibly to 16s rRNA of 30s ribosomal subunit , blocking tRNA from binding ribosome-mRNA complex

Bacteriostatic

18

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

19

Tetracyclines - main uses and resistance

Acne, CAP (doxycycline) , tick-borne diseases, PUD, STDs
- demeclocycline's only use is SIADH

Resistance due to efflux pump

20

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

21

Chloramphenicol

MOA: binds to 23s rRNA of 50s subunit inhibiting protein synthesis by blocking peptidyl transferase

Bacteriostatic

Highly bioavailable
PO= IV dosing

22

Chloramphenicol characteristics

Good CNS penetration
Hepatic all metabolized through conjugation
Useful spectrum
- streptococci, staphylococci ( Methicillin sensitive only), enterococci including VRE
-anaerobes
- some GNR

23

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

24

Quinupristin / dalfopristin

Streptogramins

MOA bind to different parts of 23s rRNA of 59s subunit, halting protein synthesis

IV only

25

Strepogramins characteristics

Bactericidal in combo vs Mssa, MRSA streptococci
Bacteriostatic vs enterococcus faecium

Hepatically metabolized
Some CNS penetration

26

Adverse effects and drug interactions of streptogramins

Phlebitis
Severe myalgias
Hepatotoxicity
Line crystallizations when mixed with saline

Drug interactions
Cyp450 3a4 inhibitors - causes increased levels of cyclosporine, nefidipine, midazolam, tacrolimus, other agents

27

Main uses and resistance to streptogramins

Vanco resistant enterococcus faecium infections

- MRSA infections in patients who cannot take other agents

Resistance due to altered target sites

28

Linezolid

Oxazolidinones

MOA: binds to 23s rRNA of 50s subunit preventing protein synthesis by blocking formation of 70s initiation complex

Binding site is distinct from their protein synthesis inhibitors

29

Oxazolidinones characteristics

Bacteria statics vs enterococci and staphylococci
Bactericidal vs streptococci

PO =IV dosing
Dual hepatic metabolism not via cyp450 and renal elimination

Weak, reversible inhibitor of monoamine oxidase

30

Oxazolidinones monoamine oxidase inhibition

-Avoid Tyramine-containing foods
-Be cautious with SSRIs, TCAs avoid other MAOIs with Linezolid therapy
- pressor effects may increase

31

Oxazolidinones spectrum and ae

Spectrum :
Gram-positive aerobes - staphylococci (including MRSA) , streptococci (including pcn- resistant strains) enterococci (including vre)

Ae:
Potential for increased BP with Tyramine containing foods
Myelosuppression, thrombocytopenia


Uses: MRSA or vre infections
Resistance : altered target site