LOs: 5 Flashcards Preview

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Flashcards in LOs: 5 Deck (21):
1

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

2

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)

3

5 Pharmacokinetics:
Metabolism

Minimally ex

Heavily ex

Aminoglycosides: minimal

Moxifloxacin: heavily

4

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

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

6

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

7

5 Bacteristatic

Drugs

Antibiotics that inhibit growth (most infections)

Tetracyclines
Macrolides (azithromycin, erythromycin)
Clindamycin
Linezolid
Tigecycline

8

5 Bactericidal

Drugs

Antibiotics that kill organisms (for life-threatening infections like meningitis & endocarditis)

Penicillins
Cephalosporins
Aminoglycosides
Vancomycin
Fluoroquinolones
Monobactams
Daptomycin

9

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)

10

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

11

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

12

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

13

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

14

5 Inhibitors of DNA/RNA synthesis:
Drugs

TMP/SMX
Rifamycins (rifampin)
Fluoroquinolones
Fidaxomicin

15

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

16

5 DNA damaging agents:
Drugs

Nitrofurantoin
Metronidazole

17

5 DNA damaging agents:
Nitrofurantoin

Mechanism of action

Mechanism of resistance

Reduce parent compound to form DNA damaging oxygen radicals

Inhibition of reductase activity

18

5 DNA damaging agents:
Metronidazole

Mechanism of action

Mechanism of resistance

Reduction to radical metabolites that perturb DNA function

Rare

19

5 Cell membrane damaging agents:
Drugs

Daptomycin
Polymyxins

20

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

21

5 Cell membrane damaging agents:
Polymyxins

Mechanism of action

Mechanism of resistance

Interacts w/ phospholipids, acts as cationic detergent

Altered binding site