LOs: 5 Flashcards
5 Pharmacokinetics:
Absorption
Bioavailability
Good ex
Poor ex
Bioavailability: level of drug in blood when given orally / given IV X 100%
FQ: very bioavailable
Vancomycin: poorly bioavailable
5 Pharmacokinetics:
Distribution
Volume of Distribution
Good ex
Poor ex
Volume of Distribution: assess concentrations in sequestered sites
- Small VD: contained within central compartments (bloodstream)
- Large VD: distribute to most sequestered sites (adipose tissues, CNS, etc.)
Rifampin: good CNS distribution (high VD)
Tobramycin: poor CNS distribution (low VD)
5 Pharmacokinetics:
Metabolism
Minimally ex
Heavily ex
Aminoglycosides: minimal
Moxifloxacin: heavily
5 Pharmacokinetics:
Excretion
Renally eliminated
Renal ex
Non-renal ex
Renally eliminated drugs require dosage adjustment in renal failure
Penicillin: renal
Moxifloxacin: non-renal
5 Concentration-dependent killing
Drugs
Rate of cell killing increases with each increase in peak concentration of antibiotic
Better to give a larger dose less frequently
Aminoglycosides
Daptomycin
Metronidazole
Fluoroquinolones
5 Time-dependent killing
Drugs
Rate of cell killing increases with increasing
amount of time that the concentration of antibiotic remains above a certain threshold (the MIC )
Beta-lactams
Linezolid
TMP/SMX
5 Bacteristatic
Drugs
Antibiotics that inhibit growth (most infections)
Tetracyclines Macrolides (azithromycin, erythromycin) Clindamycin Linezolid Tigecycline
5 Bactericidal
Drugs
Antibiotics that kill organisms (for life-threatening infections like meningitis & endocarditis)
Penicillins Cephalosporins Aminoglycosides Vancomycin Fluoroquinolones Monobactams Daptomycin
5 Inhibitors of cell wall synthesis:
Beta-lactam antibiotics
Drugs
Mechanism of Action
Mechanisms of Resistance
Penicillins
Cephalosporins
Carbapenems
Monobactams
Bind to & inhibit PBPs
Gram+: altered PBPs, beta-lactamases (outside cell wall)
Gram-: overexpression of efflux pumps, loss/alteration of porins, beta-lactamases (periplasmic space)
5 Inhibitors of cell wall synthesis:
Vancomycin
Mechanism of Action
Mechanisms of Resistance
Binds to D-Ala to interrupt peptidoglycan synthesis
Altered binding site & thickened cell wall
5 Inhibitors of cell wall synthesis:
Fosfomycin
Mechanism of Action
Mechanisms of Resistance
Binds to enzyme catalyzing N-acetylmuramic acid to inhibit peptidoglycan synthesis
Decreased drug uptake, target site modification, & enzymatic inactivation
5 Inhibitors of protein synthesis:
Drugs
Mechanism of action
2 types
Mechanisms of resistance
Aminoglycosides Macrolides Tetracyclines Linezolid Clindamycin Tigecycline
Inhibit ribosomal function to impair protein synthesis
50S inhibitors
30S inhibitors
Ribosomal mutation, overexpression of efflux pumps, & antibiotic-modifying enzymes
5 Inhibitors of protein synthesis:
Mechanisms of action
Linezolid
Macrolides, Clindamycin
Tetracyclines, Tigecycline
Aminoglycosides
50S inhibitor blocks initiaiton of protein translation
50S inhibitor blocks translocation of peptidyl rRNAs to inhibit elongation of peptide
30S inhibitor blocks access of tRNAs to ribosome
30S inhibitor binds 16S rRNA to mistranslate protein
5 Inhibitors of DNA/RNA synthesis:
Drugs
TMP/SMX
Rifamycins (rifampin)
Fluoroquinolones
Fidaxomicin
5 Inhibitors of DNA/RNA synthesis:
TMP/SMX: action & resistance
Rifamycins (rifampin): action & resistance
Fluoroquinolones: action
Fidaxomicin: action
Action: inhibits nucleic acid synthesis
Resistance: structural changes in target enzymes
Action: inhibits DNA-dependent RNA polymerase (RNA synthesis)
Resistance: target site mutaiton
Action: inhibits topoisomerases for DNA replication, transcription, recombination, & repair
Action: inhibits transcription of RNA polymerase
5 DNA damaging agents:
Drugs
Nitrofurantoin
Metronidazole
5 DNA damaging agents:
Nitrofurantoin
Mechanism of action
Mechanism of resistance
Reduce parent compound to form DNA damaging oxygen radicals
Inhibition of reductase activity
5 DNA damaging agents:
Metronidazole
Mechanism of action
Mechanism of resistance
Reduction to radical metabolites that perturb DNA function
Rare
5 Cell membrane damaging agents:
Drugs
Daptomycin
Polymyxins
5 Cell membrane damaging agents:
Daptomycin
Mechanism of action
Mechanism of resistance
Depolarizes cytoplasmic membrane, loss of intracellular components
Thickened clel wall, altered binding site
5 Cell membrane damaging agents:
Polymyxins
Mechanism of action
Mechanism of resistance
Interacts w/ phospholipids, acts as cationic detergent
Altered binding site
