Antibiotics: Inhibitors of DNA replication

Question 1

T/F: Use sulfonamides in combination with dihydrofolate reductase inhibitors

Answer 1

Yes, this is because there is tons of resistance if used alone

Question 2

What is the MOA of sulfamethoxazole (sulfonamide) and trimethoprim ?

Answer 2

1. SMX inhibits folic acid synthesis through competitive antagonism of dihydropteroate synthase
2. TMP is a competitive inhibitor of dihydrofolate reductase (DHFR)
   - Both inhibit folic acid synthesis and these are bactericidal

Question 3

What are indications for SMX/TMP or bactrim?

Answer 3

(+)= S. aureus (MRSA)
(-)= Haemophilus influenza, proteus mirabilis, escherichia coli, klebsiella (HPEK)
- Covers pneumocystis jiroveci that can cause PCP

Question 4

What are side effects for inhibitors of folic acid synthesis (SMX/TMP)?

Answer 4

1. GI distress (N/V/D)
2. Hypersensitivity (rash, SJS, interstitial nephritis, photodermatitis)

Question 5

What are side effects of SMX/TMP?

Answer 5

1. Hematologic like leukopenia (TMP), hemolytic anemia (in G6PD deficiency), kernicterus that can cause encephalopathy
2. Hyperkalemia
   - Can increase toxicity w warfarin and caution in using ACE inhibitors or diuretics like spironolactone
   - CI in pregnancy and infants

Question 6

What drugs are fluoroquinolones?

Answer 6

Ciprofloxacin, levofloxacin, and moxifloxacin

Question 7

What is the MOA of fluoroquinolones

Answer 7

• Direct inhibitors of bacterial DNA synthesis d/t inhibiting topo II (DNA gyrase) which allows excess supercoils= death so this is bactericidal

Question 8

Which quinolones are the respiratory quinolones?

Answer 8

Levo and moxi (this one also has anaerobic coverage)

Question 9

What are indications of fluoroquinolones?

Answer 9

“HNPEK, CAPES + intestinal pathogens + gram-positive
(+)= cipro covers bacillus anthracis
(-)= HNPEK, CAPES + intestinal (shigella, campylobacter jejuni, salmonella)
- Moxi has no pseudomonas coverage but covers B fragilis
- Levo and moxi cover staph and strep , atypicals

Question 10

What are side effects of fluoroquinolones?

Answer 10

1. GI distress (N/V/D)
2. Neurotoxicity (peripheral neuropathy, dizziness, insomnia, seizures)
   - BBW for peripheral neuropathy
3. Dermatologic (phototoxicity and rashes)
4. Musculoskeletal (tendonitis and tendon rupture)
   - BBW for both
5. QT prolongation (Tdp)
   - CI in pregnancy, tendonitis, and children
   - Interacts w antacids

Question 11

What is the MOA of metronidazole?

Answer 11

It is a prodrug that requires reduction of the nitro group (anaerobic) –> free radicals –> bacterial cell death
- Bactericidal

Question 12

What are indications for metronidazole?

Answer 12

(+ anaerobes)= DOC for C diff
(- anaerobes)= bacteroides, fusobacterium, prevotella
- Protozoa like giardia, trichomonas, entamoeba

Question 13

What are side effects of metronidazole?

Answer 13

1. GI distress (n/v/d, metallic taste, furry tongue)
2. Disulfiram reaction so caution w EtOH
3. Peripheral neuropathy
   - CIs are pregnancy, new primary malignancy (BBW), seizures, and alcoholism

Question 14

What is the MOA of rifampin?

Answer 14

Inhibits bacterial DNA dependent RNA polymerase–> inhibition of RNA synthesis

Question 15

What are indications for rifampin?

Answer 15

• Mycobacterium tuberculosis and other mycobacteria (leprosy)
• Meningococcal prophylaxis
• Haemophilus influenzae prophylaxis

Question 16

What are side effects of rifampin?

Answer 16

1. Hepatotoxicity
2. Red/orange body fluids
   - CYP450 inducer