2.3.3 Antibacterial Chemotherapy I

Question 1

Describe the structure and function of the bacterial cell wall

Answer 1

Question 2

Describe the multiple sites of inhibition by antibacterial agents

Answer 2

1. Cell wall synthesis (ICWS)
2. Membrane integrity
3. Protein synthesis
4. Nucleic acid synthesis
5. Nucleic acid integrity

Question 3

Explain the mechanisms of resistance to ICWS

Answer 3

1. No cell wall, no activation of murein hydrolases, metabollically inactive
2. Inaccessible PBPs - Gram neg or MRSA (structural change of PBP)
3. B-lactamase production (major mechanism of resistance, plasmid-mediated)

Question 4

Explain the role of the ß-lactam ring in the pharmacokinetics and pharmacodynamics of ICWS

Answer 4

The beta-lactam ring allows the antibiotic to mimic D-ala-D-ala structure of the peptidoglycan cell wall. This mimicry allows for covalent binding of PBPs which ultimately disrupts transpeptidation necessary for constructing the peptidoglycan cell wall

Question 5

Describe the role of transpeptidases/penicillin binding proteins (PBP) and murein hydrolases (autolysins)

Answer 5

PBP allows for the transpeptidation reaction necessary for construction the peptidoglycan cell wall

Question 6

Describe the chemotherapeutic spectrum of penicillins

Answer 6

Primarily gram +

Question 7

Describe the unique properties and indications for use of other ß-lactams

Answer 7

Question 8

Name the anti-pseudomonal penicillins

Answer 8

Ticarcillin, piperacillin, mezlocillin

Question 9

Name the extended spectrum penicillins

Answer 9

Ampicillin, amoxacillin, ticarcillin, piperacillin, mezlocillin

(increased gram - activity)

Question 10

What are the 2 main types of penicilin?

Answer 10

Pen G and Pen V

Question 11

Name the anti-staphylococcal penicillins

Answer 11

Nafcillin, isoxazolyl penicillins (ox-,clox-)

(beta-lactamase resistant)

Question 12

What are the two adverse effects of penicillin?

Answer 12

Question 13

What is true about cephalosporins in comparison to penicillins?

Answer 13

Poor oral absorption

More renal toxicity

Question 14

What are the general trends b/t the cephalosporin generations?

Answer 14

Question 15

Which cephalosporins belong to each of the four generations?

Answer 15

Question 16

What are the adverse effects of cephalosporin?

Answer 16

Local irritation

Renal toxicity - enhanced by aminoglycosides

Cefotetan – disulfrim effect -> bleeding and platelet disorders

Question 17

What are the monobactams and carbapenems? Give some characteristics.

Answer 17

Question 18

How does vancomycin differ from penicillin in its MOA?

Answer 18

Vancomycin inhibits transglycosylation by binding directly to the D-ala-D-ala of cell walls being synthesized

Penicillin - inhibits PBPs blocking transpeptidation

Question 19

What is the MOA of fosfomycin?

Answer 19

Inhibits cytoplasmic step in cell well precursor synthesis

Question 20

Know this chart

Question 21

What is the target of bacterial protein synthesis?

Answer 21

Targeting of 70S ribosome of bacteria (either the 30S or 50S subunit)

Question 22

What is the target of tetracycline?

Answer 22

Reversible binding of 30S ribosome

Question 23

What are the adverse effects of tetracyclines?

Answer 23

GI irritation, superinfections, impaired liver function, photosensitization, and calcium chelation

Question 24

What is the major mechanism of resistance to tetracyclines?

Answer 24

Efflux pumps

Another mechanism: altered ribosomal proteins or RNA are secondary mechanisms

Question 25

What is unique about tigecycline?

Answer 25

Not effected by the efflux pump (effective in bugs that have developed resistance to tetracyclines through efflux pumps)

Question 26

Name the macrolide antibiotics

Answer 26

Erythromycin, clarithromycin, azithromycin

Question 27

What is the target of the protein synthesis inhibitors?

Answer 27

Question 28

What are some pharmacokinetic characteristics of macrolides?

Answer 28

Question 29

What are the clinical uses and adverse effects of macrolide abx?

Answer 29

Question 30

What are the mechanisms of resistance to macrolide abx?

Answer 30

**Altered (methylated) rRNA** **Efflux pump** Esterase which hydrolyzes erythromycins (enterovacteriaceae)

Question 31

What is unique about azithromycin in comparison to other macrolides?

Answer 31

Extended half-life (2-4 days)

Question 32

What is unique about telithromycin?

Answer 32

Question 33

What is the MOA of aminoglycosides and their pharmacokinetics?

Answer 33

Question 34

What type of cell killing model is demonstrated by aminoglycosides?

Answer 34

Concentration-dependent (size of punch)

Question 35

What is the clinical usage of aminoglycosides?

Answer 35

non-resistant gram neg infections (E. coli, proteus, Pseudomonas)

Question 36

What are the main adverse effects of aminoglycosides?

Answer 36

Nephrotoxicity, ototoxicity, neuromuscular blockade

Question 37

What happens when aminoglycosides are administered alone?

Answer 37

Resistance emerges rapidly

Question 38

What is a good mneumonic for AGs?

Answer 38

"Mean" (a**min**oglycoside) GNATS caNNOT kill anaerobes. Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin Nephrotoxicity, Neuromuscular blockade, Ototoxicity, Teratogen