Antibiotics - RNA Synth Inhibitors

Question 1

For the class Rifamycins:
What is the...
1.)Name of it's drugs
2.) Spectrum and specific microbes?
3.) Mechanism of action?
4.)Mechanism of resistance by microbes?

Answer 1

1.) Rifampin (and fidaxomicin but this info is specific for Rifampin)
2.) Broad (Gram +/-), Mycobateri tuberculosis
3.) Binds to RNA pol stopping elongation of RNA
4.) Intrinsic: Different beta-sub unit of RNA pol so that riafmpin can’t bind
Acquired: mutation in rpoB gene –> no binding

Question 2

For Rifamycin:
What are the adverse effects?
Other notes?

Answer 2

AE:

• Hypersensitivity (fever, urticaria, edema, etc.)
• Hepatotoxic: It can induce Cytochrome P450 –> increased metabolism and damage to the liver
• Inhibition of RNA synth in mitochondria

Other notes:

• Turns body fluids orange-red
• No cross resistance w/other drugs

Question 3

For Fidaxomyicin (part of Rifamycin class)
what is the..
1.) Spectrum and specific microbes?
2.) Mechanism of action?
3.)Mechanism of resistance by microbes?

Answer 3

1. ) Narrow? Gram + aerobes & anaerobes
   - C. Diff (prevents recurrent infections so use over vancomycin and metronidazole)
2. ) Binds to sigma subunit of RNA pol
   - No cross reaction with Rifampin
3. ) None yet because it’s fairly new, but just wait

Question 4

For Fidaxomicin:
What are the adverse effects?
Other notes?

Answer 4

AE:

• Low bioavailability
• Nausea/vomiting

Question 5

For the class Fluoroquinolones:
What is the...
1.)Name of it's drugs
2.) Spectrum and specific microbes?
3.) Mechanism of action?
4.)Mechanism of resistance by microbes?

Answer 5

1. )
   a. Ciprofloxacin
   b. Levofloxacin
   c. Moxifloxacin
2. ) Broad (Gram +/-), Mycobateria
3. ) Binds to topoisomerase II and IV to prevent DNA synthesis
   
   • Topo II works on Gram -
   • Topo IV works on Gram +

4.) Active efflux mutations in topoisomerase

Question 6

For fluoroquinolones:
What are the adverse effects?
Other notes?

Answer 6

AE:

• Superinfections (C. diff)
• Problems with tendons and joints
• Pregnancy problems
• Prolonged QT interval
• GI problems
• Photosensitivity

Other:

• This can form chelate cations so don’t drink with dairy, Ca++, or juice
• Adjust for renal dysfunction

Question 7

For the class Sulfonamides:
What is the...
1.)Name of it's drugs
2.) Spectrum and specific microbes? Bacteriostatic or cidal?
3.) Mechanism of action?
4.)Mechanism of resistance by microbes?

Answer 7

1.) -Sulfamethoxazole* (paired with Trimethoprim to make Bactrim)
- Sulfisoxazole
-Sulfadiazine
2.) Bacteriostatic
Spectrum = UTI’s, pneumocystis, shigella, salmonella
3.) Mechanism = inhibition of folate synthesis by binding to Dihydropteroate synthetase. (It acts as a PABA analog making it a competitive inhibitor)
4.) - Increase the production of PABA
- Modify dihydropteroate synthetase so that it can’t be bound
- Increased drug efflux

Question 8

For Sulfonamides
What are the adverse effects?
Other notes?

Answer 8

AE:

• Cross reaction with drugs that have sulfonamide moieties
• Hypersensitivity (TEN, Stevens Johnson Syndrome, Rash, etc.)
• Crystalluria –> acute renal failure

Question 9

For Trimethoprim

1. ) Spectrum and specific microbes? Bacteriostatic or cidal?
2. ) Mechanism of action?
3. ) Mechanism of resistance by microbes?

Answer 9

1.) Bacteriostatic! But when paired with Sulfamethoxazole, it becomes bactericidal (they make bactrim)
Specturm: UTIs, pneumocystis, shigella, salmonella
2.) Mechanism = Blocks folate synthesis by inhibiting dihydrofolate reductase.
3.) -Increase production of dihydrofolate reductase.
-Alter the structure of dihydrofolate reductase so that it cannot be bound by the drug.

Question 10

For Trimethoprim:
AE?
Other Notes?

Answer 10

AE: Hyperkalemia (increased K+, bad for cell resting membrane potential)
Other Notes: none

Question 11

For Metronidazole:

1. ) Spectrum and specific microbes? Bacteriostatic or cidal?
2. ) Mechanism of action?
3. ) Mechanism of resistance by microbes?

Answer 11

1.) Bactericidal
Spectrum: Parasites, Anaerobic bacteria, C. diff
2.) It basically becomes reduced by ferrodoxin creating an electron sink and can form unstable metabolites in anaerobic bacteria that interfere with RNA synthesis.
3.) - Decreased uptake of metronidazole by bacteria
- Decrease in the enzyme that reduces metronidazole (ferrodoxin)

Question 12

For Metronidazole
AE?
Other notes?

Answer 12

AE: - Disulfam reaction: Creates crazy hangover if used with alcohol

• Nausea
• Diarrhea
• Headache
• Metallic Taste in mouth

Question 13

For Nitrofurantoin…

1. ) Spectrum and specific microbes? Bacteriostatic or cidal?
2. ) Mechanism of action?
3. ) Mechanism of resistance by microbes?

Answer 13

1. ) Bactericidal, Broad spectrum (Urinary Tract pathogens, E. coli, Staph)
2. ) It is reduced by bacterial flavoproteins to make really unstable intermediates that disrupt ribosomal and macro proteins in bacteria.

• This can only be used for UTIs since it is only activated in the urine!
  3. ) No real bacterial resistance just yet as it affects so many different systems in bacteria.

Question 14

For Nitrofurantoin…
AE?
Other notes?

Answer 14

AE: Vomiting
- Pulmonary toxicity

Other: Can’t be used outside the urinary tract system