Cell Wall Inhibiting Antibiotics

Question 1

Steps of cell wall synthesis

Answer 1

1) synthesis and assembly of cell wall subunits in cytosol
2) linear polymerization of subunits @ membrane
3) cross-linking of peptidoglycans

Question 2

Penicillin mechanism of action

Answer 2

Beta lactam. Irreversibly inhibits cross-linking (3) by acetylating penicillin binding proteins (PBPs) including transpeptidases. Also trigger autolytic enzymes by depressing the inhibitory action of autolysins. Leads to post-antibiotic effect.

Question 3

pen resistance

Answer 3

1) plasmid-mediated penicillinase production (as in MSSA)
2) alteration in PBPs (MRSA)
3) drug unable to penetrate (can’t enter many G- [pseudomonas] due to outer mmbr)
4) “escape”– metabolically inactive organisms can evade

Question 4

pen administration

Answer 4

Strongish acids. Pen G oral dose must be high, taken on empty stomach.
Pen V and amoxicillin have modified R-group to improve acid stability
Piperacillin- IV only
Abs throughout body water. Penetrates cells/tissues poorly, but can enter inflamed tissues (csf, joints, eye)
Insoluble salts reduce abs and extend duration

Question 5

Pen excretion

Answer 5

90% renal tubular excretion

Question 6

PenG/V

Answer 6

G: hydrolyzed by acid and enzymes. used IV for serious infections
V: acid resistant. Better oral abs for mild-mod abs

Question 7

penicillinase-resistant

Answer 7

dicloxacillin, nafcillin. eliminated by renal and hepatic routes, improving safety in renal insufficiency. less potent than pen G

Question 8

extended spectrum pens

Answer 8

increased hydrophilicity, allowing passage through porins. on outer membrane of G- bacteria.
Ampicillin plus/minus sublactam, Amoxacillin plus/minus clavulanic acid (B-lactamase inhibitors)

Question 9

Anti-pseudomonal pen

Answer 9

Piperacillin plus tazobactam

Question 10

Vancomycin

Answer 10

Discovered in Borneo.
Inhibits linear polymerization of PGs (step 2). IV administration. Renal excretion, so half life extended in renal failure.
Use against:
G+ cocci–MRSA, staph/streo, ampicillin resistant enterococci
anaerobes: C. diff

Question 11

Cephalosporins

Answer 11

broader G- activity compared to Pen

less susceptible to penicillinases

Question 12

1st gen. Cephs

Answer 12

Cefazolin, cephalexin. G+ cocci, G- bacilli (similar to amoxicillin)

Question 13

2nd gen. Cephs

Answer 13

Cefuroxine: G+, better than gen 1 at G-

active against anaerobes (B. fragilis)

Question 14

3rd gen. Cephs

Answer 14

Cefdinir, Ceftriaxone, Ceftazidine: Expanded G- coverage against enteric bacilli

Question 15

4th gen. Cephs

Answer 15

Cefepime: Similar to 3rd gen, more resistant to B-lactamases. Effective against Pseudomonas

Question 16

Carbapenems

Answer 16

Imipenem/Cilastatin, Meropenem, Ertapenem, Meropenem.
Stage 3 cell wall inh.–interact w/ PBPs responsible for cell wall elongation. Admin IM/IV. Given w/ renal dihydropeptidase inhibitor.