L 3-4 ICWS, Penicillins, Monobactams, Carbapenems

Question 1

What molecules make up the peptidoglycan layer of bacteria?

Answer 1

N-acetylglucosamine and N-acetylmuramic acid

Question 2

Fosfomycin

Answer 2

Inhibitor of cell wall synth.
Inhibits very early steps of peptidoglycan synth inside the cell
Not used often

Question 3

Cycloserine

Answer 3

ICWS
Structural analog of D-alanine which is incorporated into peptidoglycan synth inside the cell
Off market

Question 4

Bacitracin

Answer 4

ICWS

Prevents transport of peptidoglycan out of cell to make the wall

Question 5

Glycopeptides

Answer 5

ICWS
Vancomycin & Teicoplanin
Inhibit subunit addition to build peptidoglycan backbone

Question 6

Beta-Lactams

Answer 6

ICWS
Prevent transpeptidation
Penicillins, Cephalosporins, Carbapenems, monobactams

Question 7

Why are ICWS bactericidal and how are they affected by protein synth inhibitors?

Answer 7

ICWS are bactericidal because they cause lysis of the cell when it tries to grow and does autolysis in order to increase the wall size

Inhibitors of protein synth prevent the cell from trying to grow so ICWS can’t work until the cell breaks its own wall and tries to build it larger

Question 8

What is the defining feature of Penicillins and central to their MOA?

Answer 8

Beta-lactam ring
Essential for preventing transpeptidation
Penicillinases work by breaking this ring and inactivating the drug

Question 9

Where do Penicillins fall on the Ph scale?

Answer 9

All Penicillins are acidic

Question 10

Features of Natural Penicillins and drugs in group

Answer 10

Best against g(+), have some g(-) and some anaerobic
Quickly inactivated by beta-lactamases
No anti-pseudomonal
Eliminated in kidney–fast!
Pen G-IV
Pen V-oral
Never given intrathecal–seizures
High protein binding

Penicillin G, V

Question 11

Penicillin G

and combinations

Answer 11

Natural penicillin
IV/IM only
Many uses, only works in cells that are actively growing
Not effective in Mycoplasma or Chlamydia
+ potassium: IV/IM
+ benzathine: IM, used in long-term prophylaxis, rheumatic fever, DOC for syphilis
+ procaine: IM, makes a salt that allows prolonged effect

Question 12

Penicillin V

Answer 12

Natural penicillin

Better acid resistance allowing for oral administration

Question 13

Penicillinase resistant penicillins

Drugs and characteristics

Answer 13

Decreased g(+) coverage but increased g(-) and anaerobe compared to penicillins
DOC against penicillinase producing Staph aureus except for MRSA
Unique penicillin in that uses hepatic metabolism and renal excretion
Nafcillin: IV/IM
Oxacillin: oral
Dicloxacillin: oral
Methicillin: no longer used because of interstitial nephritis

Question 14

Nafcillin

Answer 14

Penicillinase resistant penicillin

IV/IM admin

Question 15

Oxacillin

Answer 15

Penicillinase resistant penicillin

Oral admin

Question 16

Dicloxacillin

Answer 16

Penicillinase resistant penicillin

Oral admin

Question 17

Methicillin

Answer 17

Penicillinase resistant penicillin

no longer used because of interstitial nephritis

Question 18

What penicillin causes interstitial nephritis?

Answer 18

Methicillin

This is why it is no longer on the market

Question 19

Extended spectrum penicillins

Characteristics and drugs

Answer 19

Decreased g(+) but good g(-) and anaerobe coverage
Covers E. coli, Salmonella, Shigella, H. flu, Proteus
No klebsiella
No Pseudomonas
Acid-resistant allowing oral admin
Kidney excretion

Ampicillin
Amoxicillin

Question 20

Ampicillin

Answer 20

Extended spectrum penicillin

Question 21

Amoxicillin

Answer 21

Extended spectrum penicillin

Question 22

Anti-pseudomonal penicillins

Characteristics and drugs

Answer 22

Same coverage as extended spectrum with addition of some enteric g(-)
Proteus, Enterobacter, Providencia, Serratis
Not klebsiella
Used against Pseudomonas and Acinetobacter
Sensitive to B-lactamase
Acid sensitive
Renal excretion
Must be used with aminoglycosides to prevent resistance

Piperacillin
Ticarcillin

Question 23

Piperacillin

Answer 23

Anti-pseudomonal penicillin

IV Only

Question 24

Ticarcillin

Answer 24

Anti-pseudomonal penicillin

IV Only

Question 25

What are the beta-lactamase inhibitors?

Answer 25

Clavulanic acid Sulbactam Tazobactam

Question 26

Penicillin + Beta-lactamase inhibitor combinations

Answer 26

Ampicillin + Sulbactam: parenteral, anaerobes Amoxicillin + Clavulanic Acid: (Augmentin) oral, used often in Peds clinics Piperacillin + Tazobactam: (Zosyn) IV Ticarcillin + Clavulanic Acid: (Timentin) IV

Question 27

Augmentin

Answer 27

Amoxicillin + Clavulanic acid, oral, used in peds clinics

Question 28

Zosyn

Answer 28

Piperacillin + Tazobactam: (Zosyn) IV

Question 29

Timentin

Answer 29

Ticarcillin + Clavulanic Acid: (Timentin) IV

Question 30

What can be given to help slow the excretion of penicillins by the kidney?

Answer 30

Probenacid

Question 31

Penicillin G toxicity

Answer 31

Major problem is hypersensitivity Ampicillin rash: common 3-14 days later, not allergic, common with EBV, kids, amoxicillin also Excess Na/K causing cardiac and renal toxicity Soft frothy stools and diarrhea Superinfections of staph, pseudomonas, proteus, yeast causing enteritis

Question 32

Monobactams

Answer 32

Aztreonam (Azactam) Only one ring structure allows resistance to beta-lactamases Good g(-), poor to none g(+)/anaerobes No cross-sensitivity w/other penicillin derivatives

Question 33

Aztreonam (Azactam)

Answer 33

``` Monobactam Good resistance to beta-lactamase Good g(-) Poor g(+), anaerobes No cross-sensitivity to other penicillins ```

Question 34

Carbapenems

Answer 34

ICWS Beta-lactam dependent IV admin Similar to penicillins in coverage–broad Imipenem: requires cilastatin co-admin, causes seizures–caution in head trauma, CNS disorders, brain lesions Meropenem: not sensitive to dehydropeptidase in kidney Ertapenem: stable against beta-lactamases, broad action esp enterobacteriaceae, IV/IM

Question 35

Imipenem

Answer 35

Carbapenem Requires co-administration with Cilastatin to overcome breakdown by dehydropeptidase in the kidney Can cause seizures–caution in head trauma, CNS disorders, brain lesions

Question 36

Meropenem

Answer 36

Carbapenem Not sensitive to dehydropeptidase like Imipenem Less likely to cause seizures like Imipenem Broad spectrum

Question 37

Ertapenem

Answer 37

Carbapenem Stable against beta-lactamases Broad action, esp. against enterobacteriaceae IV/IM