Penicillins

Question 1

what does Cell Wall prevent cell from?

Answer 1

osmotic rupture b/c cell is hyperosmolar —hopefully remembering physio

Question 2

what is a Peptidoglycan cell wall?

Answer 2

it is large, covalently linked sacculus surrounding the bacterium

Question 3

what are peptidoglycan composed of?

Answer 3

1. backbone of two alternating sugars, N-acetylglucosamine and N-acetylmuramic acid
2. a chain of four amino acids that are linked to NAM
3. a peptide bridge that cross-links the tetrapeptide chains (D-gln to D-ala)

Question 4

what are the points at which abx interfere w/CW synth?

Answer 4

1. Transglycosylation-joining NAM-NAG
2. transpeptidation-cross links pentapeptides
3. NAG reduction to NAM
4. transport across the inner membrane
5. AA mimicry-pentapeptide chain

Question 5

at what point during CW synth. penicillin binding proteins (BPBs) have enzymatic action?

Answer 5

enzymatic action on transglycosylation and transpeptidation

Question 6

what is MOA of Fosfomycin?

Answer 6

inhibit one of the first steps in synth of peptidoglycan

Question 7

what is MOA of Cycloserine?

Answer 7

structural analog of the AA D-alanine

Question 8

what is MOA of Bacitracin?

Answer 8

inhibits activation of lipid carrier that moves water soluble cytoplasmic peptidoglycan subunits thru membrane

Question 9

what is MOA of Glycopeptides (vancomycin)?

Answer 9

sterically inhibit the addition of subunits to the peptidoglycan backbone

Question 10

what is MOA of ß-lactam abx?

Answer 10

prevent the cross-linking rxn called transpeptidation

Question 11

transpeptidation is performend by what?

Answer 11

transpeptidases or PBPs

Question 12

all abx inhibiting bacterial CW synth are:

a. bacticidal
b. bacteriostatic

Answer 12

A.CIDAL– cause cell death due to OSMOTIC LYSIS

Question 13

True or False?

Loss of CW integrity in presence of abx is bacteria’s own fault.

Answer 13

True. b/c it is due to bacteria’s own CW remodeling enzymes that cleave peptidoglycan bonds in the normal course of cell growth.

Question 14

what are bacteria’s remodeling enzyme called?

Answer 14

autolysins

Question 15

True or False?

autolysins are not so guilty.

Answer 15

true. bc they don’t know that CW inhibitors are present…so autolysis proceeds without normal cell-wall repair leading to weakness and lysis.

Question 16

what is MOA of protein synth inhibitors like chloramphenicol?

Answer 16

PREVENT the action of the ICWS

Question 17

what is ICWS?

Answer 17

inhibitors of cell wall synthesis

Question 18

ICWS are active against what?

Answer 18

G+, pseudomonas aeruginosa

Question 19

True or false?

ICWS are acid and penicillinase resistant.

Answer 19

True. so oral absorption

Question 20

Name 4 ß-lactam ICWS.

Answer 20

Penicilins
Caphalosporins
monobactams
carbapenems

Question 21

Name 4 NOT ß-lactam ICWS.

Answer 21

vancomycin
phosphomycin
bacitracin
cycloserine

Question 22

can you name natural penicillins?

Answer 22

Pen G
Pen V
P Pen G
B Pen

Question 23

would you name Penicillinase resistant penicilines? at least the prototype?

Answer 23

Nafcillin
Docloxacillin
Oxacillin
Methicillin

Question 24

can you name the prototype for Extended spectrum penicillin?

Answer 24

Ampicillin
Amoxicillin
Bacampicillin

Question 25

what is the prototype for Antipseudomonal penicillins?

Answer 25

**Piperacillin** Ticarcillin Mezlocillin Carbenicillin

Question 26

what are 4 categories of Penicillins?

Answer 26

Natural penicillins, penicillinase resistant, extended spectrum, antipseudomonal

Question 27

Natural Penicillins have HIGHEST activity against?

Answer 27

G+ including G+ anaerobics.

Question 28

do natural pens have G- coverage?

Answer 28

yes. some

Question 29

are natural pens inactivated by ß-lactamase?

Answer 29

YES. inactivated by ß-lactamase (penicillinase): not effective against stains of S aureus

Question 30

how is Penicillinase-resistant Pens activity against G+?

Answer 30

LOWER ACTIVITY against G+

Question 31

what is MRSA's mechanism of resistance?

Answer 31

not a/w ß-lactamse | Produces alternate PBP which decrease the affinity of ß-lactam abx to PBP

Question 32

how is extended spectrum pens' G+ and G-coverage?

Answer 32

LOWER G+ coverage EXTENDED G- coverage resistance develop frequently

Question 33

what is antipseudomonal pens' spectrum?

Answer 33

spectrum: bacteria covered by the extended spectrum pens plus some additional enteric G- bacilli

Question 34

Do natural pens have antipseudomonal activity?

Answer 34

Nope.

Question 35

how are natural pens eliminated?

Answer 35

eliminated by active transport in kidney (probenecid)

Question 36

how is natural pens CNS penetration?

Answer 36

poor.

Question 37

which natural pen can be given orally?

Answer 37

Pen V because it is acid resistant.

Question 38

are penicillinase resistant pens resistant to penicillnase?

Answer 38

YES!...duh!!

Question 39

do penicillinase resistant pens have G- coverage?

Answer 39

some.

Question 40

can penicillinase resistant pens be given orally?

Answer 40

only some are acid stable and highly protein bound.

Question 41

what are penicillinase resistant pens DOC for ?

Answer 41

MSSA

Question 42

how are penicillinase resistant pens excreted?

Answer 42

Hepatic metabolism and renal excretion

Question 43

can ß-lactam be used to treat MRSA?

Answer 43

NO ß-lactam can be used to treat MRSA except ceftaroline

Question 44

do extended spectrum pens have antipseudomonal activity?

Answer 44

NO antipseudomonal activity

Question 45

are extended spectrum pens susseptible to ß-lactamase?

Answer 45

susceptible to ß-lactamase

Question 46

can extended spectrum pens be given orally?

Answer 46

acid resitant--so oral

Question 47

how are extended spectrum pens excreted?

Answer 47

urinary excretion

Question 48

what are extended spectrum pens DOC for?

Answer 48

Lysteria infection

Question 49

Rash due to what abx is not hypersensitivity?

Answer 49

ampicillin

Question 50

what is the major use of antipseudomonal pens?

Answer 50

major use: pseudomonas aeruginosa and acinetobacter

Question 51

are antipseudomonal pens susceptible to ß-lactamase?

Answer 51

yes. susceptible to ß-lactamase

Question 52

can antipseudomonal pens be given orally?

Answer 52

NOPE! acid sensitive

Question 53

how are antipseudomonal pens excreted?

Answer 53

renal excretion

Question 54

how should we use antipseudomonal pens to prevent resistance?

Answer 54

must be used in combination w/aminoglycosides to prevent resistance.

Question 55

what is the purpose of ß-lactamase inhibitors?

Answer 55

b/c most of pens are susceptible to ß-lactamase, addition of ß-lactamase inhibitors extends the spectrum of these agents

Question 56

what are the down sides of ß-lactamase inhibitors?

Answer 56

however not all ß-lactamases are inhibited by these products and bacteria may develop resistance independent upon ß-lactamase production such altered PBP production, MRSA

Question 57

what are some of ß-lactamase inhibitors?

Answer 57

clauvulanic acid, sulbactam, tazobactam

Question 58

what are some of the pens that ß-lactamase inhibitors are added to?

Answer 58

ampicilin, amoxicillin, ticarcillin or piperacillin

Question 59

what are some mechanisms of bacterial resistance for pens?

Answer 59

1. inactivation by bacterial ß-lactamase 2. decreased permeabilty in G- 3. alterations in PBPs so pens cannot bind like in MRSA 4. autolytic enzymes not being activated so forming tolerant such Listeria and staph. 5. lack of cell wall

Question 60

what are some toxicity of pens?

Answer 60

allergy all form---remember ampicillin rash is not an allergy electrolyte imbalance GI problems superinfections

Question 61

penicilins pharmacokinetic summary:

Answer 61

``` good tissue penetration poor CNS penetration mostly renal elimination filtration and tubular excretion probenecid inhibits renal elimination ```