Antibiotics

Question 1

penicillins

Answer 1

Beta-lactam - inhibits transpeptidation (cell wall)

Natural: Pen G, Pen V (best for G+)
Beta-lactamase resistant: nafcillin, oxacillin, cloxacillin
G+ and G-: ampi-, pipera-, mezlo-, ticarcillin
Acid resistant/oral: amoxicillin, pen V, oxacillin
Pen + beta-lactamase inhib: Augmentin (amox/clav), ampicillin + sulbactam, piperacillin + tazobactam

Question 2

penicillin resistance?

Answer 2

beta-lactamases
lack of PBPs
autolysin mutations “tolerance”

Question 3

cephalosporins

Answer 3

Beta-lactams (cell wall), but less sensitive to beta-lactamases

1G: prophylaxis only - cephalexin, cephalothin, cefazolin
2G: G+ and G-: cefaclor, cefuroxime, cefoxitin
3G: G+ and G-, w/ pseudomonas:

Question 4

monobactams

Answer 4

monocyclic beta-lactam ring (cell wall), resistant to beta-lactamases for G- only

aztreonam

Question 5

carbapenems

Answer 5

beta lactam (cell wall) - G+ and G-, but may be toxic 
allergy, toxicity - seizures 

imipenem, ertapenem, meropenem (less toxicity)

Question 6

bacitracin

Answer 6

blocks dephosphorylation of bactroprenol (cell wall)
topical, G+
poorly absorbed, renal toxicity

Question 7

glycopeptides

Answer 7

bind aa side chain - block transglycosylation and transpeptidation (cell wall) for G+

Vancomycin, telavancin

Question 8

glycopeptide resistance

Answer 8

use -Ala-Lac instead of -Ala-Ala for pentapeptide - via chromosomal vanB and plasmid vanA genes

Question 9

how can you overcome vancomycin resistance?

Answer 9

replace disaccharide with -H

replace =O in amide binding site with =N

Question 10

cycloserine

Answer 10

D-ala analog - inhibits Ala racemase (cell wall), but neurotoxic

sometimes for UTI, 2nd line TB drug

Question 11

Mycobacterium drugs

Answer 11

1. isoniazid (INH), ethionamide - inhibit pyridoxine step in mycolic acid synthesis
2. ethambutol (EMT) - inhibit arabinogalactan synthesis
3. pyrazinamide (PZA) - inhibits trans-translation
4. rifampicin (RMP)

Question 12

polymyxins/ colistin

Answer 12

dissolve phosphatidlethanolamine, part of G- (cell membrane)
toxic - topical only, often w/ bacitracin and neomycin

Question 13

daptomycin/ cubicin

Answer 13

cyclic lipopeptide - dissolves in membrane, disrupts membrane potential (cell membrane)

G+, MRSA - must be IV, synergy with beta-lactams

Question 14

sulfonamides (sulfone) and trimethoprim, aka bactram/SxT

Answer 14

inhibit steps in path: PABA -> DHF -> THF -> pyrimidines (antimetabolite)

uses: Nocardia, Salmonella, shigella, UTIs

Question 15

SxT resistance

Answer 15

overproduction of PABA, altered enzymes

Question 16

(fluoro)quinolones

Answer 16

inhibit DNA gyrase (nucleic acid inhibitor) but can get prolonged QT segment (EKG)

Use: not very soluble, use fluoro instead (ciprofloxacin and derivatives) for UTI, G-, G+, Pseudomonas

ciprofloxacin, moxifloxacin

Question 17

(fluoro)quinolone resistance

Answer 17

altered DNA gyrase, drug exclusion

Question 18

fidaxomycin/ dificid

Answer 18

targets “switch region”/ loading clamp of RNA pol - prevents interaction of RNA pol and DNA (nucleic acid inhibitor)

Question 19

rifamycin

Answer 19

blocks RNA pol elongation subunit (nucleic acid inhibitor) - but makes sweat/urine orange!

rifampin, rifabutin, rifaximin

use: Mycobacterium + INH, crosses BBB, blocks assembly of poxviruses

Question 20

rifamycin resistance

Answer 20

altered RNA pol beta subunit

Question 21

metronidazole

Answer 21

partially reduced complex with ferredoxin interacts with DNA and breaks DNA strands - free radical (nucleic acid inhibitor)

use: antiprotozoal, anaerobes (first time for C. diff)

Question 22

aminoglycosides

Answer 22

bind 30S subunit, block initiation by preventing attachment of tRNA-fMet (protein synthesis inhibitor)

streptomycin, neomycin, gentamicin, tobramycin, amikacin

use: G- enterics, synergy with cephs/pens (facilitate entry)

Question 23

aminoglycoside resistance

Answer 23

altered P12 ribosomal protein
aminoglycosidases
altered permeability

Question 24

tetracycline

Answer 24

inhibits binding of aa-tRNA to A-site of 30S subunit (protein synthesis inhibitor) but side effects: toxicity, dizzy, tinnitus, fluorescent teeth, NOT FOR PREGGERS

doxycycline, tigecycline

use: rickettsia, chlamydia, mycoplasmas

Question 25

chloramphenicol

Answer 25

inhibits peptidyl transferase rxn - 50S (protein synthesis inhibitor) no longer a drug of choice, toxicity and resistance - chloramphenicol acetyl transferase (CAT)

Question 26

macrolides

Answer 26

bind rRNA, inhibit translocation - 50S (protein synthesis inhibitor) - prolonged QT interval (EKG), increased CV risk erythromycin, clarithromycin, azithromycin (Z-pack) use: G+, some G-

Question 27

macrolide resistance

Answer 27

methylation of rRNA

Question 28

lincosamides

Answer 28

bind rRNA, inhibit translocation - 50S (protein synthesis inhibitor) - same as macrolides clindamycin use: anaerobes, anti-malarial, doesn't cross BBB

Question 29

nitrofurantoin

Answer 29

inhibits 30S (protein synthesis inhibitor) use: UTIs

Question 30

mupirosin

Answer 30

inhibits Ile-tRNA (protein synthesis inhibitor) use: topical, G+

Question 31

streptogramins/ synercid

Answer 31

``` inhibits 50S (protein synthesis inhibitor) quinupristin + dalfopristin ``` use: VRE, VRSA

Question 32

oxazolidinones - linezolid

Answer 32

inhibits 50S (protein synthesis inhibitor) use: VRE, MRSA

Question 33

methenamine

Answer 33

releases formaldehyde in acidified urine use: UTIs

Question 34

how do you target persistor cells?

Answer 34

C10, BF8 - wake up persistor cells, then use other abx to target the newly growing cells

Question 35

which drugs should not be used for pregnant women?

Answer 35

- amikacin - kanamycin - streptomycin - tobramycin - sulfa drugs - all tetracyclines - erythromycin - macrobid and nitrofurantoin

Question 36

which drugs are cell wall inhibitors?

Answer 36

- beta-lactams (penicillins, cephalosporins, monobactams, carbapenems) - bacitracin - glycopeptides (vancomycin, telavancin) - cycloserine

Question 37

which drugs are cell membrane disruptors?

Answer 37

- polymyxins (colistin) - daptomycin (cubicin) - sulfonamides (sulfones) + trimethoprim (aka bactram, SxT)

Question 38

which drugs are nucleic acid inhibitors?

Answer 38

- (fluoro)quinolones (ciprofloxacin, moxifloxacin) - fidaxomycin (dificid) - rifamycin (rifampin, rifabutin, rifaximin) - metronidazole

Question 39

which drugs are protein synthesis inhibitors?

Answer 39

- aminoglycosides (streptomycin, neomycin, gentamycin, tobramycin, amikacin) - tetracycline (doxycycline, tigecycline) - chloramphenicol - macrolides (erythromycin, clarithromycin, azithromycin) - lincosamides (clindamycin) - nitrofurantoin - mupirosin - streptogramins/ synercid - oxazolidinones (linezolid) - methenamine