Antibiotic drug classes & mechanisms

Question 1

What are the possible reasons for adverse reactions to antibiotics?

Answer 1

Membrane interacting antibiotics may interact with patient membranes at high concentrations

Breakdown and release of bacterial components can cause a reaction

Question 2

What are narrow vs broad spectrum antibiotics?

Answer 2

Narrow spectrum
- Targets narrow group of bacteria (i.e. either Gram positive or Gram negative)

Broad spectrum
- Targets Gram +ve & –ve bacteria

Question 3

What is a bacteriocidal antibiotic?

Answer 3

Kills the organism

Example penicillin’s, cephalosporin’s

Question 4

What is a bacteriostatic antibiotic?

Answer 4

Drugs that temporarily inhibit the growth of an organism (i.e. reversible if removed).

E.g. Tetracycline’s, Chloramphenicol

rely on host systems to reduce & remove bacteria that are not growing
- not very effective in immuno-compromised patients

Question 5

What is the MIC of an antibiotic?

Answer 5

(minimum inhibitory concentration):
concentration required at site of infection to achieve bacterial inhibition.

Question 6

What is the MBC of an antibiotic?

Answer 6

(minimum bactericidal concentration):
concentration required at site of infection to kill the bacteria

Question 7

What is concentration dependant killing?

Answer 7

where drug has to be at or above critical concentration to have an impact. It relates to getting enough of the drug bound to enough to the targets in the bacteria to have an effect.

Question 8

What are the main antibiotic targets of action?

Answer 8

Inhibition of protein synthesis

Inhibition of cell membrane function

Inhibition of cell wall synthesis

Interference with other pathways

Inhibition of DNA dependent RNA polymerase

Disruption of DNA structure

Question 9

Give examples of antibiotics that inhibit protein synthesis

Answer 9

Chloramphenicol
Lincosamides
Macrolides
Amino glycosides
Pleuromutilin
Tetracyclines
Nitrofurans

Question 10

Give examples of antibiotics that inhibit cell membrane function

Answer 10

Polypeptides
Antimicrobial peptides

Question 11

Give examples of antibiotics that inhibit cell wall synthesis

Answer 11

B-lactam antibiotics
Vancomycin
Bacitracin

Question 12

Give examples of antibiotics that inhibit DNA dependant RNA polymerase

Answer 12

Rifampicins

Question 13

Give examples of antibiotics that disrupt DNA structure

Answer 13

Nitroimidazoles
Metronidazole

Question 14

What is peptidoglycan

Answer 14

unique to bacteria (good target)

polymer of sugars & amino acids that forms mesh-like cell wall

The polysaccharide chains cross linked by interlinking peptides

Question 15

How do beta-lactam antibiotics target the bacterial cell wall (peptidoglycan)?

Answer 15

Inhibit transpeptidase (Penicillin-Binding Protein), preventing peptide cross-link formation in peptidoglycan

Result: Weakened cell wall & bacterial lysis due to osmotic pressure.

Question 16

How does penicillin resistance develop in bacteria?

Answer 16

Production of beta-lactamase enzymes that break beta-lactam ring

Methicillin-resistant strains have altered PBP due to mec gene, making them resistant to beta-lactams

Question 17

What are cephalosporins, and how are they classified?

Answer 17

Cephalosporins are beta-lactam antibiotics divided into 5 generations based on their spectrum of activity:

1st Gen: Effective against Gram-+ve bacteria, moderate against Gram- -ve

2nd Gen: Targets both Gram-+ve (less effective) & Gram- -ve

3rd Gen: Broad-spectrum, reserved for critical cases.

4th Gen: Even broader spectrum, used sparingly due to resistance concerns.

5th Gen: Effective against MRSA, used only in critical human cases.

Question 18

What is the role of methicillin in combating beta-lactamase-producing bacteria?

Answer 18

Methicillin is resistant to beta-lactamase enzymes, but resistance can develop due to altered PBPs

Question 19

What are examples of antibiotics that inhibit protein synthesis?

Answer 19

30S subunit inhibitors:
- Tetracyclines: Block tRNA attachment.
- Aminoglycosides: Cause irreversible inhibition of protein synthesis.

50S subunit inhibitors:
- Macrolides: Block translocation
- Chloramphenicol: Prevent peptide bond formation.
- Lincosamides: Similar to macrolides but with a different spectrum.

Question 20

What is the mechanism of action for ribosome-targeting antibiotics?

Answer 20

These antibiotics bind to specific sites on ribosomal RNA or ribosomal proteins within 30S or 50S subunits, physically blocking ribosome’s function & inhibiting protein synthesis.

Question 21

How can bacteria develop resistance to ribosome-targeting antibiotics?

Answer 21

Mutations in ribosomal RNA or ribosomal proteins alter binding sites, reducing antibiotic efficacy

These modifications increase MIC required for effectiveness, leading to resistance.

Question 22

How do Quinolones work?

Answer 22

Inhibit DNA gyrase & topoisomerase, disrupting DNA supercoiling & replication

Spectrum: Broad, effective against Gram- -ve & some Gram- +ve bacteria.

Question 23

What is the mechanism and common use of TMPS (sulphonamides and trimethoprim)?

Answer 23

TMPS is synergistic combination targeting 2 points in same metabolic pathway, inhibiting folic acid synthesis in bacteria.

Competitive inhibitors

It is effective due to its dual mechanism of action.

Question 24

What is the mechanism of action for nitroimidazoles?

Answer 24

produce reactive reduction products that interact with & damage bacterial DNA, leading to bacterial death.

Question 25

How does Rifampicin work?

Answer 25

Inhibits DNA dependent RNA polymerase => blocks initiation of protein synthesis

Question 26

What are cationic antimicrobial peptides, and how do they work?

Answer 26

Disrupt bacterial membranes by interacting with lipids.

Often used topically in dermatology (e.g., ear infections).

Question 27

Why do antimicrobial peptides (AMPs) not harm eukaryotic cells?

Answer 27

Eukaryotic cell membranes contain zwitterionic phospholipids & cholesterol, which are absent in bacteria.

These components provide intrinsic resistance to AMPs.

Question 28

How does the site of infection influence antibiotic activity?

Answer 28

Anaerobic conditions: Nitroimidazoles are activated.

Aerobic conditions: Aminoglycosides require oxygen for uptake.

Question 29

Why are nitroimidazoles effective under anaerobic conditions?

Answer 29

Nitroimidazoles require anaerobic conditions to be reduced to their active form by anaerobic bacteria

Once activated, they interact with and damage bacterial DNA.

Question 30

Why are aminoglycosides less effective under anaerobic conditions?

Answer 30

Aminoglycosides rely on aerobic electron transport chain to enter bacterial cells

In anaerobic conditions, bacteria downregulate part of transport chain, reducing aminoglycoside uptake.

Question 31

What is the key factor for time-dependent antibiotics?

Answer 31

most important factor is time serum concentration remains above Minimum Inhibitory Concentration (MIC)

Increasing concentrations above MIC doesn’t enhance killing

e.g. Beta-lactams, macrolides

Question 32

What is the key factor for concentration-dependent antibiotics?

Answer 32

most significant factor is achieving high peak concentration at binding site

Killing increases with higher concentrations

e.g. Aminoglycosides, fluoroquinolones