Antimicrobial Pharm

Question 1

Cell wall synthesis inhibitors

Answer 1

Beta-lactam

Question 2

Folate synthesis inhibitors

Answer 2

Sulfonamides

Trimethroprim

Question 3

DNA gyrase inhibitors

Answer 3

Fluoroquionlones

Question 4

RNA polymerase inhibitors

Answer 4

Rifampin

Question 5

Protein synthesis inhibitors

Answer 5

Tetracyclines
Aminoglycosides
Macrolides

Question 6

Bacteriostatic

Answer 6

Inhibit/stop growth and reproduction of bacteria - works with your own immune system to remove microorganisms from the body

Question 7

Bactericidal

Answer 7

Kill bacteria by interfering with a process essential for life (concentration-dependent or time-dependent)

Question 8

Time-dependent

Answer 8

Killing effect is directly proportional to the amount of TIME the drug concentration at the site of infection is ABOVE the MIC of the organism

Question 9

MIC

Answer 9

Lowest concentration of a drug that inhibits bacterial growth

Question 10

Concentration-dependent

Answer 10

Bacterial kill increases with increasing levels of drug; have to avoid toxicity

Question 11

Which type (static vs. cidal) should be used in patients with impaired immune defense mechanisms?

Answer 11

Bactericidal (required for endocarditis, meningitis, and neutropenic cancer pt)

Question 12

Five principle MOAs in antimicrobial classification

Answer 12

1. ) Inhibition of cell wall synthesis
2. ) Disruption of cell membrane function
3. ) Inhibition of protein synthesis
4. ) Inhibition of nucleic acid synthesis
5. ) Action as antimetabolites

Question 13

Common target for agents that inhibit cell wall synthesis

Answer 13

Peptidoglycan synthesis and incorporation into bacterial cell wall

Question 14

How do beta-lactam antibiotics work?

Answer 14

• They bind to PBPs (transpeptidase enzymes)
• PBP is unable to crosslink peptidoglycan chains
• Bacteria unable to synthesize a stable cell wall
• Weakened cell wall leads to lysis of bacteria from osmotic pressure

Question 15

What is the key chemical structure found in every beta-lactam antibiotic?

Answer 15

Beta-lactam ring with beta-lactam bond (N-C=O)

Question 16

Beta-lactamases

Answer 16

Bacteria can encode this enzyme that can cleave the beta-lactam bond; drug resistance

Question 17

MRSA

Answer 17

Beta-lactam antibiotics WON’T WORK!!

-PBP is mutated in MRSA so no beta-lactam antibiotics can bind since the target site is altered

Question 18

Beta-lactam antibiotics groups and characteristics

Answer 18

• Natural penicillins, Cephalosporins, Carbapenems, and Monobactams
• Beta-lactams are bactericidal and time-dependent killers

Question 19

Penicillin groups and drugs

Answer 19

• Natural penicillins (penicillin G)
• Penicillinase-resistant penicillins or Antistaphylococcal penicillins (nafcillin)
• Extended-spectrum penicillins (amoxicillin)
• Antipseudomonal penicillins (ticarcillin)

Question 20

Penicillin G active against…

Answer 20

Gram+ bac

Question 21

Cephalosporins groups and drugs

Answer 21

First gen (cephalexin)
Second gen (cefoxitin)
Third gen (ceftriaxone)
Fourth gen (Cefepime)

Question 22

First gen mainly active against…

Answer 22

Gram+ cocci

Question 23

With each generation of cephalosporins there is increasing…

Answer 23

• Activity against g- bac and less activity against g+
• Resistance to beta-lactamases
• Ability to cross BBB

Question 24

Carbapenem drug

Answer 24

Imipenem

Question 25

Monobactam drug

Answer 25

Aztreonam

Question 26

Vancomycin action and characteristics

Answer 26

- Inhibits transglycosylase (prevents building block bound to phospholipid carrier from binding to growing peptidylglycan chain) - Does not cross lipid membrane of g- - Acquired resistance most often due to amino-acid alterations in side chain peptidoglycan building blocks (mutates binding site so Vanco can't bind)

Question 27

Bacitracin action and characteristics

Answer 27

- Interferes with transport of peptidoglycan precursors across cytoplasmic membrane (cell wall synthesis inhibited) - Toxicity limits use to topical apps - Common ingredient in non-prescription in first-aid ointments (Neosporin)

Question 28

Agents that act directly on the cell membrane...

Answer 28

- Disrupt the integrity of the cell membrane (increase permeability leading to leakage of intracellular components) - polymyxin and daptomycin - Bactericidal and concentration-dependent killers

Question 29

Colistin (polymyxin E)

Answer 29

- Binds to LPSs and phospholipids on outer cell membrane of gram- - competitvely displaces Ca and Mg from PO4 groups of membrane lipid - Leads to disruption of outer cell membrane, leakage of intracellular contents, bacterial death

Question 30

MOA of daptomycin

Answer 30

- daptomycin binds to the membrane - Ca allows many daptomycin to recruit and "poke a hole" in the membrane - Leakage of K>>depolarization>>arrest of cell processes>>cell death

Question 31

Agents that inhibit bacterial protein synthesis....

Answer 31

- Translation inhibitors that target either 30S or 50S bacterial ribosome subunits - Typically reversible inhibitors - Generally bacteriostatic

Question 32

Classes of antibiotics that inhibit bacterial protein synthesis and their drugs

Answer 32

- Tetracyclines (doxycycline) - Macrolides (erythromycin) - Aminoglycosides (gentamycin - exception to rule: AGs irreversibly inhibit protein synthesis and are generally bactericidal)

Question 33

Inhibition of DNA gyrase (affect nucleic acid metabolism)

Answer 33

- Bacterial DNA is negatively supercoiled - Supercoiling maintained by gyrase (topoisomerase) - Inhibition of gyrase and type IV topoisomerase interferes with DNA replication, causes cell death - Eukaryotic topoisomerases differ in structure

Question 34

Drug that inhibits RNA polymerase

Answer 34

Rifampin

Question 35

Drug class and drug that inhibits DNA replication

Answer 35

Fluoroquinolones; ciprofloxacin

Question 36

Classes that target folic acid synthesis and their drugs

Answer 36

Sulfonamides (sulfamethoxazole) and drug: trimethoprim

Question 37

Inhibition of folate synthesis

Answer 37

Folic acid is a cofactor needed for synthesizing the building blocks of DNA; metabolic inhibitors that target folic acid synthesis are selectively toxic to bacteria because bacteria have to synthesize a large proportion of cofactors (2-step process so you need to have both drugs to stop the pathway)