Intro to Antimicrobials

Question 1

Antimicrobial Hx

Answer 1

1. Antibiotic: cmpd produces by living microorganism w/ antimicrobial activity
2. Synthetic cmpds
   A. Not true antibiotics
   B. Rational drug design, cmpd screening, serendipity

Question 2

Factors influencing MIC/MBC

Answer 2

1. MIC/MBC not best indicator of clinical efficiency
2. Antimicrobials must reach MIC/MBC at site to cause infection
3. Challenge
   A. Absorption and distribution
   B. Bone, CNS, adipose

Question 3

Effective dose must balance toxicity

Answer 3

1. Mechanism targeted has similar mammalian counterpart
   A. Mitochondria, protein synthesis
2. Off-target effects

Question 4

Non-dose dependent toxicity

Answer 4

1. Allergic rxns

2. Idiosyncratic - pharmacogenomic

Question 5

Bacteriocidal

Answer 5

Kills microbe

Question 6

Basteriostatic

Answer 6

Stops growth

1. Can -> resistance in immunocompromised pts.

Question 7

Chemotherapeutic spectrum

Answer 7

Range of organisms antimicrobial can fight

Question 8

Broad spectrum

Answer 8

Wide range

1. Gram (+) and (-) and some parasites

Question 9

Narrow spectrum

Answer 9

Few organisms

Question 10

Extended spectrum

Answer 10

Intermediate range

1. Usually narrow modified to include more

Question 11

Protein synthesis inhibitors

Answer 11

1. 30S subunit
  A. Tetracycline
  B. Aminoglycosides
2. 50S subunit
  A. Macrolides
  B. Clindamycin
  C. Linezolid
  D. Chloramphenicol
  E. Streptogramins
3. Bacteriostatic

Question 12

Resistance mech to protein synthesis inhibitors

Answer 12

1. Dec. porins 
  A. Gram (-)
2. Inc. export of drug by efflux pumps
3. Microbial enzymes alter/destroy drug
4. Alter target proteins
5. Alter targeted pathways

Question 13

Ways translation is inhibited by antimicrobials

Answer 13

1. Drugs bind ribosomes
   A. Prevent translocation (erythromycin)
   B. Disrupt tRNA interaction (tetracycline)
2. Prevent peptide chain formation
   A. Chloramphenicol

Question 14

Cell wall synthesis inhibitors

Answer 14

1. Mech: prevent peptidoglycan formation
  A. Prevent cross-linking 
    1. Transpeptidase links D-alanine on Muriel monomers
2. Destabilization = bactericidal
  A. H2O in -> cell bursts
  B. Most effective in growing pop
3. Beta lactams
4. Glycopeptides
5. Lipopeptides
6. Bacitracin
7. Polymyxins

Question 15

Beta lactams

Answer 15

Largest class

1. Penicillins
2. Cephalosporins (biggest subclass)
3. Carbapenems
4. Monobactams

Question 16

Penicillins

Answer 16

Beta lactam
1. Natural: gram (+) and syphilis
2. Extended: gram (+) and (-)
  A. Aminopenicillins
  B. Amoxicillin
  C. Ampicillin

Question 17

Cephalosporins

Answer 17

Beta lactam, biggest subclass

1. 5 generations: altered spectra and resistance to degradation by some bacteria
2. Ceph or cef in name

Question 18

Carbapenems

Answer 18

Beta lactam

1. Combo therapy common
2. Potent
3. Broad spectrum

Question 19

Monobactams

Answer 19

1. Not true beta lactams (missing a ring)

2. Narrow spectrum: gram (-)

Question 20

Allergic response to beta lactams

Answer 20

1. Beta lactams + human protein -> allergic response
   A. Anaphylaxis
   B. Cytolytic anemia
2. Allergy = contradiction for using any beta lactam
   A. Exception: monobactams usually safe

Question 21

Bacterial resistance to beta lactams

Answer 21

1. Open ring -> inactive
2. Strategies to combat lactamases
   A. Combo therapy: stronger given w/ weaker one
   
   1. Weak competitively inhibits lactamases
   2. Strong allowed to work
   3. Ex: amoxicillin/clavulanate
      B. Chem mod of antibiotic to change enzyme affinity to access to ring
   4. Steric hinderance
   5. Ex: methicillin

Question 22

Glycopeptides

Answer 22

1. Bind D-alanine needed for peptidoglycan crossing
2. One of last effective drugs against MRSA infections
3. Vancomycin
   A. Only gram (+)
   B. Resistant organisms don’t use D-alanine

Question 23

Lipopeptides

Answer 23

Daptomycin
1. Insert into plasma membrane -> disrupt wall
  A. Gram (+)
  B. Vancomycin-resistant strains
  C. Bactericidal

Question 24

Bacitracin

Answer 24

1. Prevents peptidoglycan subunits transfer to cell surface

2. Bactericidal

Question 25

Polymyxins

Answer 25

Small, (+) peptides 1. Disrupt membrane structures 2. Bactericidal 3. Gram (-)

Question 26

DNA/RNA stability and synthesis inhibitors

Answer 26

1. Direct= bactericidal A. Target polymerase B. Target stability/structure of DNA C. Resistance 1. Antibiotic modification 2. Altered protein targets 3. Protective proteins 2. Indirect = bacteriostatic A. Competitive folate synthesis inhibitors B. Act syngergistically 1. Sulfonamide: inhibit dihydropteroate synthesis 2. Trimethoprim: inhibit dihydrofolate reductase C. Resistance: inc. bioavailability of precursors 3. Broad spectrum

Question 27

Reasons to use combo therapy

Answer 27

1. Broad spectrum therapy in seriously ill pts 2. Treat polymicrobial infection 3. Dec. emergence of resistant and multi-drug resistant strains 4. Dec dose-related toxicity 5. Inc inhibition/killing

Question 28

Additive effects

Answer 28

1. Beta-lactamase inhibitors + beta-lactam drugs | A. Amoxicillin/clavulanate

Question 29

Antagonistic effects

Answer 29

1. Bacteriostatic + cell way synth inhibitors | A. Tetracycline dec efficiency of penicillins