Antibiotic Agents Against Bacterial Synthesis

Question 1

Identify the major classes of antibiotics that target the 30S ribosomal subunit (2). Briefly describe each.

Answer 1

Aminoglycosides - block initiation step, ribosomal translation step and cause mistranslation
Tetracyclines - block peptide elongation step @ 30S subunit

Question 2

Identify the major classes of antibiotics that inhibit the 50S ribosomal subunit (4). Briefly describe each

Answer 2

1. Macrolides - blocks ribosomal translocation step; bacteriostatic
2. Clindamycin - blocks translocation step; bacteriostatic
3. Streptogramins - block translocation and inhibit peptide elongation; bacteriocidal vs strept and most staph
   4, Linezolid - blocks initiation step; bacteriocidal vs strept

Question 3

Identify the major classes of antifolates that inhibit DNA biosynthesis (2).

Answer 3

1. Sulfonamides - competitive antagonists of dihydropteroate synthase
2. Trimethoprim - competitive antagonist of dihydrofolate reductase

Question 4

Identify the major classes of DNA gyrase and Topo IV inhibitors (5)

Answer 4

Fluoroquinolones - inhibit topoisomerase II in Gram-negative bacteria and topoisomerase IV in Gram-positive bacteria.

Question 5

Describe the spectra of antibacterial activity, clinical uses and common adverse reactions of: Aminoglycosides.

Answer 5

Spectra of activity - only bactericidal protein synthesis inhibitor;
Clinical uses - streptomycin = 2nd line Rx for TB + used in combination; Tobramycin and Gentamicin = used against Gram negative + combo with B-lactams;
Adverse effects - Ototoxic, Nephrotoxic

Question 6

These aminoglycosides works great against Gram-negative bacteria and is used in combination with beta-lactams for synergistic effects.

Answer 6

Tobramycin and Gentamicin

Question 7

This aminoglycoside is not as potent as Gentamicin but is resistant to enzymes that block it.

Answer 7

Amikacin - used if Gentamicin and Tobramycin fails

Question 8

These drugs are used topically (have no effect systemically) and found in eyedrops.

Answer 8

Neomycin and Kanamycin

Question 9

Describe the toxic effects of aminoglycosides.

Answer 9

Nephrotoxic - reversible damage of kidneys upon discontinuation of therapy
Ototoxicity - irreversible auditory/ vestibular damage; tinnitus
toxicity that can occur at >5 days

Question 10

Describe the spectra of antibacterial activity, clinical uses and common adverse reactions of: Tetracyclines.

Answer 10

Spectra - bacteriostatic + BROAD spectrum (aerobic, anaerobic, Gram +/-), blocks elongation @ 30S;
Clinical uses - Rickettsial infections, typhus, Q fever, Chlamydia, respiratory tract infections, community-acquired staph, acne, Lyme disease
Adverse reactions - GI disturbances, binds calcium to stain teeth in children, photosensitization, liver disturbances

Question 11

This type of tetracycline is taken oral/IV with LONG half-life to treat anthrax, malaria and Lyme Disease

Answer 11

Doxycycline

Question 12

These drugs are reserved to treat multidrug resistant bacteria such as MRSA, VRE and penicillin-resistant strept

Answer 12

Tigecycline and Eravacycline

Question 13

List at least 3 adverse effects of using Tetracyclines.

Answer 13

1. Binds calcium to deform developing teeth and bony structures
2. Photosensitization
3. Hepatotoxic effects

Question 14

Describe the spectra of antibacterial activity, clinical uses and common adverse reactions of: Macrolides.

Answer 14

Spectra - bacteriostatic, great for aerobic Gram-positive;
Clinical Uses - respiratory infections, community-acquired ammonia, bronchitis
Adverse effects - GI effects and Liver toxicity (better than tetracyclines)

Question 15

This 50S inhibitor bacteriostatic drug is a new antibiotic used to treat MRSA, VRE and penicillin-resistant streptococci.

Answer 15

Linezolid

Question 16

How do antifolate drugs differ from that of DNA Gyrase and Topo IV inhibitors?

Answer 16

Antifolate drugs inhibit biosynthesis of purines (block enzyme that works with folate to make DNA); whereas DNA gyrase inhibitors block bacterial DNA replication.

Question 17

Describe the spectra of antibacterial activity, clinical uses and common adverse reactions of: Sulfonamides.

Answer 17

Spectra - bacteriostatic against Gram-negative and some Gram-positives;
Clinical uses - treat UTIs, IBDs (ulcerative colitis and Chron’s)
Adverse reactions - strongly HYPER-allergenic, hives, dermatitis, poorly soluble (crystalluria = painful obstruction)

Question 18

Describe the spectra of antibacterial activity, clinical uses and common adverse reactions of: Trimethroprim.

Answer 18

Spectra - bacteriostatic against Gram-negatives and some Gram-positives OR bactericidal when combined as TMP-SMX;
Clinical uses - UTIs (E. Coli), salmonella, pneumocystis jiroveci pneumonia;
Adverse effects - rash, fever, urticaria, photosensitivity, GI effects

Question 19

A combination therapy of these drugs results in primary adverse reactions of megaloblastic anemia and leukopenia if used >5 days.

Answer 19

TMP-SMX

Question 20

Inhibition of _____ interferes with separation of replicated chromosomal DNA into daughter cells. Whereas, inhibition of ________ prevents the relaxation of supercoils of DNA needed for DNA replication.

Answer 20

Topoisomerase IV;

DNA Gyrase

Question 21

Describe the spectra of antibacterial activity, clinical uses and common adverse reactions of: Fluoroquinolones.

Answer 21

Spectra - bacteriocidal, blocks Gyrase in Gram-negative and blocks Topo IV in Gram-positive;
Clinical uses - UTIs, diarrhea, Shigella, Salmonella, Toxigenic E. coli; Ciprofloxacin used to treat anthrax (by Bacillus anthracis);
Adverse reactions - GI disturbances (nausea, vomiting + diarrhea), can damage growing cartilage and cause arthropathy.

Question 22

This fluoroquinolone is used to treat anthrax caused by…

Answer 22

Ciprofloxacin is prophylactic drug used to treat anthrax caused by Bacillus anthracis.

Question 23

Levofloxacin, Gemifloxacin and moxifloxacin are aka __________ fluoroquines. Describe what they treat.

Answer 23

Respiratory fluoroquinolones (FQs) used to treat upper and lower respiratory tract infections.

Question 24

Respiratory FQs can be used to treat _______ which is an opportunistic bacteria known to infect the lungs of patients with Cystic Fibrosis.

Answer 24

Pseudomonas aeroginosa

Question 25

What antimicrobial, when overused can lead to C. difficile colitis? Define the function.

Answer 25

Clindamycin = 50S ribosomal inhibitor; It’s used to treat infections by aerobic and anaerobic Gram-positive bacteria. These include Clostridium perfringens, inflammatory acne and

Question 26

What drug is main choice to treat anthrax (by Bacillus anthracis)? How does it work?

Answer 26

Ciprofloxacin (a fluoroquinolone) inhibits DNA Gyrase and Topoisomerase IV.

Question 27

Define the selective toxicity. Provide a few targets.

Answer 27

Describes the properties that certain cell types make that make them targets for antimicrobial therapy. Some targets include the cell wall, fungal membranes, bacterial ribosomes and DHF reductase.