Micro Chapter 5

Front 1

First Antibiotic?

First true antibiotic?

Back 1

"antimetabolite" sulfonamide by Domagk in 1934

Penicillin, Fleming 1928

Front 2

Describe the relationship between early Sulfonamide and PAB

PAB and Folic Acid?

Back 2

PAB was structurally similar and when administered competitively inhibited Sulfonamide

Non-competitively, if adequate folic acid was available drug would have no effect

Front 3

Why do sulfonamides work?

Back 3

Humans require presynthesized folic acid while Bacteria must make their own and cannot absorb Folic Acid itself. Therefore inhibition of the synthesis only targets bacterias

Front 4

Limitations of drug efficacy?

Back 4

speed of work, sensitivity of microbe, side effects of host

Front 5

-Cidal vs -Static

Back 5

cidals better when bodies defenses are low

static give time for body to get rid of organisms

two definitions not absolute

Front 6

What is Trimethoprim's mechanism of action?

Why isn't this dangerous for humans?

Back 6

Halts the function of folic acid by inhibiting dihydrofolate reductase, preventing conversion to tetrahydrofolate

The amount needed for 50% inhibition of bacteria is extremely lower than in mammals

Front 7

Why is tetracycline not damaging to humans?

Back 7

Despite requiring the same dose for efficacy, bacteria concentrate it in their cells while mammals do not

Front 8

Penicillins/Cephalosporins
Resistance Mechanism

Back 8

Hydrolysis of B-lactam ring by B-lactamase

Front 9

Methicillin
Resistance Mechanism

Back 9

Change in Penicillin-Binding Protein (PBP)

Front 10

Tetracyclines
Resistance Mechanism

Back 10

Efflux pump pushes drug out of cell

Front 11

First Antibiotic?

First true antibiotic?

Back 11

"antimetabolite" sulfonamide by Domagk in 1934

Penicillin, Fleming 1928

Front 12

Describe the relationship between early Sulfonamide and PAB

PAB and Folic Acid?

Back 12

PAB was structurally similar and when administered competitively inhibited Sulfonamide

Non-competitively, if adequate folic acid was available drug would have no effect

Front 13

Why do sulfonamides work?

Back 13

Humans require presynthesized folic acid while Bacteria must make their own and cannot absorb Folic Acid itself. Therefore inhibition of the synthesis only targets bacterias

Front 14

Limitations of drug efficacy?

Back 14

speed of work, sensitivity of microbe, side effects of host

Front 15

-Cidal vs -Static

Back 15

cidals better when bodies defenses are low

static give time for body to get rid of organisms

two definitions not absolute

Front 16

What is Trimethoprim's mechanism of action?

Why isn't this dangerous for humans?

Back 16

Halts the function of folic acid by inhibiting dihydrofolate reductase, preventing conversion to tetrahydrofolate

The amount needed for 50% inhibition of bacteria is extremely lower than in mammals

Front 17

Why is tetracycline not damaging to humans?

Back 17

Despite requiring the same dose for efficacy, bacteria concentrate it in their cells while mammals do not

Front 18

Penicillins/Cephalosporins
Resistance Mechanism

Back 18

Hydrolysis of B-lactam ring by B-lactamase

Front 19

Methicillin
Resistance Mechanism

Back 19

Change in Penicillin-Binding Protein (PBP)

Front 20

Tetracyclines
Resistance Mechanism

Back 20

Efflux pump pushes drug out of cell

Front 21

Penicillins/Cephalosporins
Resistance Mechanism

Back 21

Hydrolysis of b-lactam ring by b-lactamase

Front 22

Methicillin
Resistance Mechanism

Back 22

change in PBP

Front 23

Tetracyclines

Back 23

Efflux pump pushes out of cell

Front 24

Aminoglycosides (gentamicin, tobramycin, streptomycin)

Back 24

enzymatic modification by Rplasmid, reduces ribosome affinity and decreases xport into cell

Front 25

Sulfonamides

Back 25

sulf resistant dihydropteroate synthase

Front 26

Trimethoprim
Resistance Mechanism

Back 26

" resistant dihydrofolate reductase

Front 27

Erythromycin
Resistance Mechanism

Back 27

Methylation of 23S rRNA

Front 28

Chloramphenicol

Back 28

Acetylation of OH groups, interference of cell transport

Front 29

Oxazolidinones - Linezolid

Back 29

23S rRNA mutation

Front 30

Quinolones (ciprofloxacin)

Back 30

mutation of genes for DNAgyrase(G+) + topoisomeraseIV(G-)

Front 31

Vancomycin

Back 31

Change in binding site in peptidoglycan target (daladala to daladlac)

Front 32

How do B-lactams become broad spectrum

Back 32

They are able to target gram(-)s by modification of the lactam ring

Front 33

Modification of second generation B-lactams? Third?

Back 33

2nd - Gram(-)
3rd - CNS entry

Front 34

Difference between B-lactamases of Gram(+) and Gram(-)?

Back 34

Gram(+)s release a drug-dose dependent amount into the medium, cannot be overcome by high doses

Gram(-)s produce a set amount and retain it in their periplasm, can be overcome with high doses

Front 35

Non-B-lactamase defenses (+/-)

ex of seriousness

Back 35

+s have modified the PBP
-s have mutations in their porins

PRSP and MRSA

Front 36

Biggest risk in ABs currently?

Back 36

Superstrain of S.Aureus which has gained the vancomycin resistance from enterococci

MRSA + VRE --> VRSA

Front 37

Secondary mechanism of resistance to Fluoroquinolones? (not gyrase/topo mutation)

Back 37

Efflux pump development in gram(+) S.aureus and gram(-)P.Aeruginosa

Front 38

Toxicity of Tetracycline?

Back 38

Chelation of Magnesium with bone/teeth malformation in children

Front 39

Aminoglycosides
1 - Mechanism (3 step vers)
2 - Two forms of resistance + microbes

Back 39

1 - (A) traverse of Gram(-) Outer membrane
(B) Entrance/Use of bi-directly active transport system into cell
(C)Binding to 30S ribosome and stopping of transcription at initiation step

Resistance 1 is inactivation of transport by Obligate Anaerobics

Resistance 2 is by acetyl/phosphoryl/adenyl-ation of Aminoglycosies, inactivating them

Front 40

What is special about the macrolide Telithromycin?

Back 40

It binds to two places on the 23S ribosome, avoiding the effects of the methylation.

It also is not effected by the efflux pumps

Front 41

Macrolide resistance?

Back 41

By methylation of the 23S ribosome within the 50S by methylase

methylase activity low until macrolides administered

Front 42

Linezolid Resistance? (Why is Linezolid special)

Back 42

Resistance is formed by mutation of the 23S ribosome

being completely synthetic, linezolid avoids all preexisting resistance strategies

Front 43

Antifungal agents + Mechanism
1 - Polyenes
2 - Imidazoles
3 - echinocandins

Back 43

1 - Polyenes attack ergosterol rather than cholesterol. Is toxic to RBCs and Kidney
2 - imidazoles attack cytochrome P450 demethylase
3 - echinocandins - target is B-Glucan, not present in human cells

Front 44

Synergism? Example

Back 44

Greater effect seen with combo

penicillin + gentamicin on enterococci

normally gentamicin cannot enter cells, penicillin allows entry of gentamicin

Front 45

Antagonism? Example

Back 45

One drug negates the other

Penicillin + Tetracycline

Tetracycline stops the growth which is essential for the -cidal effects of penicillin, results in only bacteriostatic fx