5 – Antimicrobials

Question 1

How do antibiotics work?

Answer 1

• Attack physiological processes or structures unique to bacteria
  o Cell wall
  o Cell membrane
  o Nucleic acid synthesis, metabolism and organization
  o Protein synthesis

Question 2

How do bacteria resist antibiotics?

Answer 2

• Decreased permeability (prevent entry)
• Active efflux (pump out)
• Enzymatic degradation/alteration (destroy)
• Target modification (disguise)
• Alternate pathways (do something else)
• Resistance by absence (lacking target)
• *INTRINSIC or GAIN GENETIC COMPETENCE

Question 3

Minimum inhibitory concentration (MIC)

Answer 3

• Minimum drug concentration that will INHIBIT an organism’s growth

Question 4

Minimum bactericidal concentration (MBC)

Answer 4

• Minimum drug concentration that will KILL an organism

Question 5

Bacteriostatic

Answer 5

• When MBC > 4x MIC

Question 6

Bactericidal

Answer 6

• When MBC <(=) 4x MIC

Question 7

Concentration dependent drugs

Answer 7

• Relies on maximally exceeding organism MIC at site of infection
  o may be able to give 1 or 2 big doses/day

Question 8

Time dependent drugs

Answer 8

• relies on how long (% of day) drug concentrations exceeding organism MIC are maintain at site of infection
  o may require multiple doses/day

Question 9

Beta-lactams

Answer 9

• cell wall synthesis INHIBITORS
  o transpeptidases and carboxypeptidases
• superfamily of antimicrobials
• Beta-lactam/inhibitors combinations
  o Act by irreversibly binding to the serine catalytic site of certain bacterial beta-lactamases (NOT all beta-lactamases can be INHIBITED)

Question 10

CEPHALOSPORINS

Answer 10

*as increase generation, improvement against Gram-negatives and increasing resilience to beta-lactamases

Question 11

Other beta-lactams

Answer 11

• Very broad spectrum
• Most Gram-positive, negative and anaerobes
• Example
  o Ertapenem
   No activity against enterococci or Pseudomonas
  o Monobactams
   Only gram-neg activity
• Including against Pseudomonas aeruginosa
  o Carbapenems

Question 12

TETRACYCLINES

Answer 12

• Broad spectrum agents
  o Gram-positive activity more limited than Gram-negative
  o Resistance is common (susceptibility testing is essential)
• *increase in lipophilicity
  o Better cross the membrane
   Higher concentrations intracellularly and sequestered sites

Question 13

(FLURO) QUINOLONES

Answer 13

• Inhibits DNA gyrase and topoisomerase IV
• Prevents replication and organization (supercoiling) – bactericidal
• *at very high drug concentrations, the drugs can prevent the transcription of important activities=decreased drug activity

Question 14

AMINOGLYCOSIDES

Answer 14

• Bind to 30S ribosomal subunit
• Also effects ETC, DNA metabolism and cell membrane
• BACTERICIDAL
• *only aerobic bacteria
• Often paired with beta-lactams which will break down the cell wall so they can enter

Question 15

MLSBK

Answer 15

• Reversible binding to 50S ribosomal subunit
• *BACTERIOSTATIC

Question 16

PHENICOLS

Answer 16

• *reversible binding to 50S ribosomal subunit
• BACTERIOSTATIC

Question 17

Folate synthesis inhibitors

Answer 17

• PABA to go into cycle and becomes an INACTIVE intermediate=pathway shuts down
  o Competitive inhibition
• Diaminopyrimidines
  o Directly inhibits the enzymes

Question 18

Nitroimidazoles (Metronidazole)

Answer 18

• Low molecular weight
• Readily enters cells
• ONLY KILLS ANAROBES: Under anaerobic conditions: metronidazole is reduced
  o Intermediate compounds include unstable free radicals
   Radicles bind to DNA and prevent synthesis
• BACTERICIDAL
• Banned in food animals

Question 19

Pharmacodynamics

Answer 19

• Interactions of a drug with its target, mechanisms of action and correlation of actions with effects
  o Ex. Drug-Bug interactions

Question 20

Pharmacokinetics

Answer 20

• Process of absorption, distribution, metabolism and excretion of a drug.
  o How the compound moves through the body
  o Ex. Host-Drug interactions