Inhibitors of Nucleic Acid Synthesis (Week 4)

Question 1

Rifamycin- Rifampin

Answer 1

• bactericidal
• binds bacterial RNA polymerase, blocks mRNA elongation
• Gram positive and Gram negative (Mycobacteria tuberculosis)
• turns body fluids orange-red

Question 2

Fidaxomicin

Answer 2

• bactericidal
• inhibits RNA polymerase by binding to sigma subunit
• narrow spectrum to spare gut flora
• Gram positive anaerobes (C. difficile)

Question 3

Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)

Answer 3

• bactericidal
• inhibits DNA replication by binding bacterial DNA topoisomerase
• broad spectrum Gram positive and Gram negative atypical organisms (Mycoplasma)
• don’t take with calcium, iron, aluminum, or zinc = chelate cations

Question 4

Sulfonamides (Sulfamethoxalzole, sulfisoxazole, sulfadiazine)

Answer 4

• bacteriostatic
• PABA analog, competitive inhibitor of Dihydropteroate synthesis
• indirect inhibition of DNA synthesis

Question 5

Trimethoprim

Answer 5

• bacteriostatic
• inhibits dihydrofolate reductase
• indirect inhibition of DNA synthesis

Question 6

Trimethoprim + sulfamethoxazole (Bactrim)

Answer 6

• sequential blockade is bactericidal
• sequential blockage of the folate synthesis pathway
• broad treatment of UTIs (Shigella, Salmonella, Pneumocystis)

Question 7

Metronidazole, Tinidazole

Answer 7

• bactericidal
• metronidazole reduced (electron sink)
• activated form generates free radicals leading to DNA strand breaks and cell death
• Spectrum: protozoa, Anaerobic bacteria including C. difficile

Question 8

Nitrofurantoin

Answer 8

• bactericidal
• reduced by bacteria flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other macromolecules
• leads to inhibition of synthesis of DNA, RNA, cell wall, and protein
• Broad spectrum- rapidly excreted in urine in active form (ineffective for infections outside of lower urinary tract)

Question 9

aminoglycosides and tetracycline

Answer 9

-inhibit 30S subunit of prokaryotic ribosome

Question 10

linezolid, macrolides, chloramphenicol, clindamycin, quinupristin/dalfopristin

Answer 10

-inhibit 50S subunit of prokaryotic ribosome

Question 11

Linezolid

Answer 11

• inhibits protein synthesis by binding to the 23S ribosomal RNA on the 50S subunit
• prevents formation of initiation complex
• Spectrum: reserved for drug resistant Gram positive (MRSA, Vancomycin Resistant Enterococci)

Question 12

Aminoglycosides- gentamicin, neomycin, amikacin, tobramycin, streptomycin

Answer 12

-bactericidal
-prevents formation of initiation complex, causes misreading of mRNA and induces early termination
-Spectrum: gram negative aerobic
Amikacin is less susceptible to enzyme inactivation and broader spectrum including Pseudomas
-administered as single large dose

Question 13

Tetracyclines- tetracycline, doxycycline, minocycline

Answer 13

• interferes with aminoacyl tRNA insertion into acceptor site during chain elongation
• bacteriostatic
• bind 30S preventing attachment of aminoacyl-tRNA
• Spectrum: broad initially but resistance (B. burgdorferi, H. pylori, Mycolasma pneumonia)

Question 14

Chloramphenicol

Answer 14

• bacteriostatic
• binds 50S ribosomal subunit preventing peptide bind formation (peptidyltransferase can’t associate with amino acid substrate)
• Spectrum: extended but use is limited due to sever side effects (bone marrow depression and aplastic anemia)

Question 15

Macrolides- erythromycin, azithromycin, clarithromycin

Answer 15

• bacteriostatic
• inhibits translocation by binding 23S rRNA of the 50S subunit (translocation = dipeptide tRNA moves from A to the P site and ribosome moves 1 codon along the mRNA
• Spectrum: broad coverage of respiratory pathogens, Chlamydia

Question 16

Lincosamide: Clindamycin

Answer 16

• bacteriostatic
• blocks translocation at 50S ribosomal subunit
• Spectrum: Gram positive including anaerobic. treat acne

Question 17

Stretogramins: Quinupristin/ Dalfopristin

Answer 17

• bactericidal for some when used together
• binds 50S to inhibit translocation
• Spectrum: reserved for infections caused by multiple drug resistant Gram positive bacteria

Question 18

Aminoglycoside + Penicillin

Answer 18

• combined drug therapy

- increases permeability of cell membranes increasing the ability of aminoglycosides to enter cell