Antimicrobial Therapy 3 Flashcards
Which antibiotics act on 30S Ribosomal Subunit?
- Tetracyclines
2. Aminoglycosides
What is the MOA for Tetracyclines?
Inhibit bacterial protein synthesis by binding to 30S ribosome; Causes misreading of genetic code
What are the Pharmacokinetics of Tetracyclines?
- Bacteriostatic
- Broad Spectrum
- Requires Active and passive transport to cross cell wall
When do you not use Tetracyclines?
Don’t use in pregnancy and when breastfeeding; Chelates with calcium inhibits bone and teeth formation in fetus. Avoid until eruption of permanent teeth
What are the mechanisms of resistance for Tetracyclines?
- Enzymatic inactivation
- Impaired influx by protein pump
- Proteins protecting binding site Tet(M) mutation
What are the side effects of Tetracycline?
- NVD
- Photosensitivity
- Teeth discoloration
- Bone deformities
- Liver toxicity
Discuss Tigecycline
Withstands resistance that affects other tetracyclines.
- Broad spectrum
- Great tissue penetration
What is the MOA for Aminoglycosides?
Used for Aerobic Gram-
- Inteferes with initiations complex
- Induces misreading of mRNA
- Breaks up polymers into nonfunctional monomers
What are the pharmacokinetics of Aminoglycosides?
- Bactericidal
- Concentration depedent killing
- Small Volume of distribution; cant cross BBB
- Post antibiotic effect
What are the mechanisms of resistance for Aminoglycosides?
- Enzymatic inactivation
- Impaired entry into cell
- Ribosome mutation
How do aminoglycosides get into bacterial cell?
- Passive diffusion across Gram- OM
2. Active transport across CM via oxygen dependent process
What are the side effects of Aminoglycosides?
- Neuromuscular blockade
- Ototoxicity
- Nephrotoxicity
Which drugs act on the 50s Ribosomal subunit?
- Macrolides
- Clindamycin
- Streptogramins
- Oxazolidinones
What is the MOA of Macrolides?
Binds to 50S ribosome by blocking transpeptidation and translocation reaction.
What are the pharmacokinetics of Macrolides?
- Bacteriostatic
2. Good distribution
What is the resistance of Macrolides?
- Reduced permeability
- Esterases hydrolyze macrolides
- Production of methylase that modifies ribosome.
What are the side effects of Macrolides?
- Abdominal pain
- Cholestatic hepatitis
- Prolonged Qtc interval
- Skin rash
Discuss Fidaxomicin
- Used for C. difficile diarrhea
- Bacteriocidal
- Large MW
What is the MOA of Clindamycin?
Inhibits translocation reactions on 50s ribosomes
What are the pharmacokinetics of Clindamycin?
- Bacteriostatic
- Good distribution
- Treats abscesses
What are the side effects of Clindamycin?
- Skin rash
- Nausea
- Diarrhea
What is the MOA for Streptogramins?
Dalfopristin- Causes conformational change in ribosome preventing peptide chain formation.
Quinupristin: Blocks elongation of peptide; Binds 50s
What are the pharmacokinetics of Streptogramins?
- Bactericidal
- Inhibits Cyp450
- Synergistic combination
What are the side effects of Streptogramins?
- Thrombocytopenia
- Hyperbilirubinemia
- Arthralgia-Myalgia Syndrome
What is the MOA for Oxazolidinones?
Linezolid: Binds 23s ribosome subunit preventing formation of ribosome complex
Tedizolid: Binds P site of 50s subunit of bacterial ribosome; Prevents protein synthesis
Are Oxazolidinones Bacteriostatic?
YES
What are the side effects of Oxazolidinones?
- Thrombocytopenia
- Neutropenia
- Serotonin Syndrome
What is the MOA of Fluroquinolones?
Inhibit bacterial topoisomerases
What are the pharamcokinetics of Fluroquinolones?
- Bactericidal
- Time and concentration dependent killing
- Renally cleared except Moxifloxacin
Which drugs inhibit DNA replication?
Fluoroquinolones, Metronidazole, and Rifampin
What are the mechanisms of resistance of Fluoroquinolones?
- Altered target sites
- Altered Cell wall permeability
- Active efflux pump
What are the side effects of Fluoroquinolones?
- Photosensitivity
- QT prolongation
- May damage cartilage; Avoid in pregnancy
What is the MOA for Metronidazole?
Disrupts DNA and inhibits nucleic acid synthesis in anaerobic bacteria
What are the pharmacokinetics of Metronidazole?
- Bactericidal
2. Good for anaerobic infections
What are the side effects of Metronidazole?
- Dry mouth
- Pancreatitis
- Nausea
What is the MOA of Rifampin?
Binds beta-subunit of DNA-dependent RNA polymerase; Inhibits RNA synthesis (No effect on elongation)
What are the pharmacokinetics of Rifampin?
- Bactericidal
- Good bioavailibility
- CYP450 inducer
What is the resistance to Rifampin?
Point mutation to beta subunit of RNA polymerase
What are the side effects of Rifampin?
- Orange body fluid
- Rash
- Thrombocytopenia
- Cholestatic jaundice
What is the MOA of Nitrofurantoin?
Interferes with metabolism, protein and cell wall synthesis
What are the side effects of Nitrofurantoin?
- Nausea
- Vomiting
- Neuropathies and hemolytic anemia in G6PD deficiency.
