Antimicrobials

Question 1

Pre-antibiotic era

Answer 1

-We were powerless against infections. Wounds=death; TB in urban areas; Sexually transmitted infections
-used vials of mercury injected into blood or urethra
-Antibiotics not used until 1940s

Question 2

Fleming’s Observation

Answer 2

-found that mould on petri dish was preventing the growth of staphylococcus colonies (lysis)

Question 3

When was drug discovery at its peak?

Answer 3

From 1940s-1960s… then few drugs developed.

Been a few more developed since 2010

Question 4

How do antibiotics work?

Answer 4

-They attack physiological processes or structures unique to bacteria

Structures include:
-cell wall
-cell membrane
-nucleic acid synthesis, metabolism, organization
-protein synthesis

Question 5

How do bacteria resist antibiotics?

Answer 5

1. Prevent entry (decreased permeability)
2. Pump out (active efflux)
3. Destroy (enzymes)
4. Disguise (target modification)
5. Use alternative pathways

6.Lack target (remove target receptors to allow for resistance)

Question 6

Minimum inhibitory concentration

Answer 6

-minimum drug concentration that will inhibit an organism’s growth

**reported on log scale

Question 7

Minimum bactericidal concentration

Answer 7

-minimum drug concentration that will kill an organism

Question 8

Bacteriostatic vs. bactericidal

Answer 8

Bacteriostatic: When MBC> 4x MIC

Bactericidal: When MBC less than or equal to 4x MIC

Question 9

Concentration dependent drugs

Answer 9

-activity relies on maximally exceeding organism MIC at site of infection

Question 10

Time dependent drugs

Answer 10

Activity relies on how long drug concentrations exceeding organisms MIC are maintained at site of infection

Question 11

Beta-lactams

Answer 11

Antimicrobials that are cell wall synthesis inhibitors by binding to the penicillin binding proteins within the wall.
**prevents final stage of peptidoglycan synthesis

Super family of antimicrobials

Question 12

Types of beta-lactams

Answer 12

-penicillins

-cephalosporins

-Carbapenems

-beta-lactamase inhibitors

Question 13

Beta-lactams basica structures

Answer 13

-All have a 4 membered ring (beta lactam ring)

**common structure that bacteria can try and avoid

Question 14

beta-lactam/inhibitor combinations

Answer 14

Act by irreversibly binding to the serine catalytic site of certain (NOT ALL) bacterial beta-lactamases
>only active against class A enzymes

Question 15

beta-lactam/inhibitor combinations that are available

Answer 15

1. Clavulanic acid (amoxicillin and clavulanic acid)
2. Sulbactam (ampicillin + sulbactam)
3. Tazobactam (piperacillin +tazobactam)

Question 16

Increasing generations of cephalosporin

Answer 16

As generations increase, get improved activity against gram negatives and increasing resilience to beta-lactamases

Question 17

Carbapenems

Answer 17

-reserved for human medicine to prevent any resistance selection in animals

-very broad spectrum, most gram positive, gram negative, and anaerobes

Question 18

Tetracyclines

Answer 18

-bind to 30S ribosomal subunit reversibly- bacteriostatic
prevents protein synthesis

-Increasing lipophilicity from tetra, to doxy, to minocycline. Means they are better able to cross cell membranes

Question 19

Fluoroquinolones

Answer 19

Inhibits DNA gyrase and topoisomerase IV, preventing replication and organization (supercoiling)= bactericidal

Question 20

Fluoroquinolones drug concentration

Answer 20

Too low and too high concentrations of these drugs results in poor drug activity because these drugs will interfere with DNA and prevent transcription

Question 21

Aminoglycosides

Answer 21

-bind to 30S ribosomal subunit but also effects ETC, DNA metabolism, and cell membranes
**bactericidal

Question 22

MLSBK

Answer 22

-reversible binding to 50S ribosomal subunit
*bacteriostatic

Question 23

Phenicols

Answer 23

-reversible binding to the 50S ribosomal subunit
**bacteriostatic

-banned in food animals, rare idiosyncratic aplastic anemia in people (destruction of bone marrow)

Question 24

Folate synthesis inhibitors

Answer 24

1. Sulfa
   - competitive inhibition of PABA in folate pathway
2. trimethoprim AND Sulfamethoxazole
   -target gram positive, gram negative, MRSA/MRSP, parasites (some protozoas and toxoplasma)

Question 25

Nitroimidazoles (Metronidazole)

Answer 25

-low molecular weight molecule (171.16 Da)
-readily enters cells, is reduced and forms unstable free radicles which bind to DNA and prevent synthesis
-very overused antibiotic
-used to fight anaerobes
-bactericidal
-banned in food animals

Question 26

Antimicrobial resistance

Answer 26

-resistance is natural
-we select for resistance with antimicrobial usage, we dont create it

Question 27

Pharmacodynamics

Answer 27

The interactions of a drug or substance with its target, mechanisms of action and correlation of actions with effects

“drug-bug interactions”

Question 28

Pharmacokinetics

Answer 28

The processes of absorption, distribution, metabolism, and excretion of a drug or substance.

“host-drug interactions”