Antibiotics

Question 1

What is the biochemical basis of antimicrobial action (broadly)?

Answer 1

Since organisms need to take up many types of biomolecules to grow and divide, antimicrobial agents interfere with specific processes that are essential for growth and/or division.

Question 2

What are bacteriocidal antimicrobial agents?

Answer 2

Chemotherapeutic agents capable of causing irreversible damage or death to the organism. The agents are independent of the host’s immune system in their action on the organism. May harm host at high level.

Question 3

Bacteriostatic

Answer 3

Agents that inhibit the growth and/or reproduction of the infecting agent. These agents are dependent on the host’s immune system for elimination of the microorganism.

Question 4

MIC

Answer 4

minimal inhibitory concentration - represents the lowest concentration of the antibiotic which prevents the organism from multiplying - not necessarily killing the organism - want trough to be above the MIC

Question 5

MBC

Answer 5

minimal bacteriocidal concentration - represents the lowest concentration which kills the organism - not relevant with bacteriostatic agents - there are certain conditions where you want the cidal concentration - bone and heart stuff

Question 6

What are the 5 modes of action of antibiotic drugs?

Answer 6

1. Inhibition of cell wall synthesis (most common mechanism - largest class of antibiotics)
2. Inhibition of protein synthesis, ribosomal function (second largest class)
3. Alteration of cell membranes (antifungal)
4. inhibition of nucleic acid synthesis
5. Antimetabolite activity, folate synthesis

Question 7

What are some ideal attributes of antibacterials?

Answer 7

selective target; bactericidal; narrow spectrum (does not kill normal flora); high therapeutic index (ratio of toxic level to therapeutic level); few adverse reactions - toxicity, allergy; various routes of administration - IV, IM, oral; good absorption (cytochrome 450) come are able to absorb things better - absorption and distribution different between children and adults; emergence of resistance is slow

Question 8

Cell wall synthesis antibiotics - inhibit the linking of NAG and NAM so that the bacteria explode

Answer 8

Glycopeptides: vancomycin, BETA LACTAMS: penicillins, cephalosporins, monobactams, carbapenems

Question 9

Folic acid metabolism antibiotics

Answer 9

trimethoprim, sulfanamides

Question 10

Cell membrane antibiotics

Answer 10

polymyxins

Question 11

DNA, nucleic acid antibiotics

Answer 11

quinolones, rifampin

Question 12

What are the four antibiotics (inhibitors of cell wall synthesis) that are beta lactams?

Answer 12

Penicillin, cephalosporin, monobactam, carbapenems

Question 13

Why are the beta-lactams grouped together?
Cidal or Static?
Are they toxic? Expensive? Soluble?

Answer 13

1. Share a structural feature; the beta lactam ring
2. cidal
3. non-toxic, inexpensive, soluble

Question 14

What to penicillin binding proteins do?

Answer 14

Are a set of transpeptidases that catalyze the final cross-linking reactions of peptidoglycan synthesis - bind to penicillin - b lactam ring inhibits transpeptidease - B lactams are structurally analogous to D- Ala - D- Ala so PBPs react with these antibiotics by cleaving the beta lactam bond and form a stable intermediate that does not react further - acylation of PBPs by beta lactams inactivates the enzyme

Question 15

1. How many different classes of penicillins exist?
2. How many different generations of cephalosporins exist?
3. what is the most powerful beta lactam?

Answer 15

1. six
2. four, newer class with activity against MRSA, higher the generation more resistant to destruction
3. Carbapenems

Question 16

What is one type of glycopeptide?

Answer 16

vancomycin - effective against gram positives only, the drugs enter without any problem because peptidoglycan does not act as a barrier for the diffusion of these molecules. Not effective against gram negatives - molecule can not pass through porins - inhibits cell wall synthesis

Question 17

What are the major antibiotics for the inhibition of protein syntheses?

Answer 17

Tetracyclines, Aminoglycosides (gentamycin, tobramycin), Macrolides (erythromycin, azithromycin, clarithromycin),

Question 18

Tetracyclines:

1. cidal or static?
2. What is it used for?

Answer 18

1. static - broad spectrum, but resistance is common which limits its use
2. Chlamydia, rickettsiae, mycoplasma - not recommended for pregnant women and children because of the toxicity on bones and teeth of fetus

Classification of tetracyclines based on length of activity in the body and absorption from GI tract - doxycline is long acting, has long serum half life - less frequent dosing

Question 19

Aminoglocosides:

1. Method of action
2. Cidal or static?

Answer 19

1. Bind to the RNA of the 30s ribosomal sub-unit that affects all stages of normal protein synthesis -
2. Cidal

Renal and ototoxicity - need to monitor blood levels

Question 20

Macrolides:

1. Cidal or static?

Answer 20

1. static - their spectrum of activity is limited to gram (+) cocci such as streptococci and staphylococci, also active against anaerobes

Question 21

Anti-metabolites: Folate pathway inhibitors
What is folic acid used for?
Why is folic acid a good target?

Answer 21

1. Folic acid is essential for the synthesis of adenine and thymine
2. Humans do NOT synthesize folic acid, good selective target

Question 22

Sulfonamides/ Trimethoprim - folate pathway inhibitors

1. Cidal or static?
2. what is the mode of action of these drugs?

Answer 22

1. Sulfa and trimet are both static, but when used in combination = cidal
2. Drug resembles a microbial substrate and competes with that substrate for the limited microbial enzyme. The drug ties up the enzyme and blocks a step in metabolism.

Question 23

Sulfonamides:

1. Do they have good urine solubility?
2. What are they used for?

Answer 23

1. Yes

2. Acute urinary tract infections, patients allergic to penicillins, otitis media

Question 24

Fluroquinolones:

What is their mode of action?

Answer 24

Inhibitor of nucleic acid synthesis.
Act by targeting topoisomerases, responsible for cutting one of the chromosomal DNA strands at beginning of supercoiling process

Question 25

What is a factor that affects whether a drug exhibits bacteriostatic or bactericidal activity?

Answer 25

The antimicrobial concentration at the site of action

Antimicrobials may be bacteriostatic at low concentrations but cidal at high concentrations

Question 26

What is a broad spectrum antibiotic?

Answer 26

One which is active against a wide range of bateria - usually both gram pos and gram neg

Question 27

What is a narrow spectrum antibiotic?

Answer 27

Active against a select group of bacterial types