Drug Mech: Quiz 2

a. tetracyclines

Recall the following:

· BACTERIOSTATIC & BACTERICIDAL EFFECTS OF ANTIBIOTICS

• Penicillins (bactericidal)
• Tetracyclines (bacteriostatic)
• Aminoglycosides (bactericidal)
• Polypeptides (bactericidal)
• Sulfonamides (bacteriostatic)
• Quinolones (bactericidal)

• A. vancomycin is bactericidal
• cephalosporin is bactericidal

d) all of the above

He mentioned in class that vanco was bactericidal, but I don't know about the other drugs. For instance, cephalosporins may be grouped with penicillins? bacitracin...I would have to look up to know which family it is even in. I don't even know for sure which family vanco is in.

Like an exam II question:

a. polypeptides

a. quinolones

sulfonamides indirectly, but not directly inhibit nucleic acid synthesis. c and d do not.

d. amoxicillin

classification question:

e. all of the above

• like exam I question!
• 1) know the static/cidal effect at clinical dose.
• 2) know something about the mechanism of action.

• a. penicillin inhibits cell wall + aminoglycoside injects crap in, so synergistic
• b. Septra! Synergistic: sequential steps
• c. Synergistic because one will help the other
• d. antagonistic because amoxicillin is cidal, tetra is static, so they antagonize the cidal effect of beta lactam.

so d. amoxicillin + tetracycline

• a. amoxicillin + clavulanic acid
• b. ampicillin + amoxicillin (not a good combo...these drugs do same thing, so they will end up competing)
• c. piperacillin (penicillin) + imipenem (beta lactam: carbapenem; potent induce of beta lactamase) imipenem will indirectly destroy the other...so antagonistic
• d. vancomycin (inhibits cell wall synthesis, so bactericidal) + tetracycline (inhibits cell division), so the two will antagonize each other's actions.

combination A: FIC index = 0.1 (one drug is facilitating the action of the other)

Knowing scale is not enough....know how synergism and antagonism can occur.

• because anything 0.5 or less is synergistic
• 1 is indifferent.
• 10 and 100 are antagonistic.

c. quinolones

What about macrolides?

d. all of the above

b. target modification

He described the mechanism of resistance, now you categorize it. Be familiar with these words because they don't explain what is going on when you read the drug monograph.

• Recall four mechanisms of action:
• target modification
• altering metabolic pathway

• 1) Contributes to microbial resistance. Contributes to sensitive bacterial species, favoring growth
• 2) favors toxicity

• 1) If infection is caused by two or more organisms
• 2) synergism: one antibiotic enhances the other

note antagonism and indifference are not an advantage!

Kills wide range of species (gram negative and gram positive). Tetracyclines and Aminoglycosides are broad spectrum.

Active against a small number of organisms. Penicillin-G for example is considered narrow spectrum.

Erythromycin of Macrolides, Rifampins.

• 1) add antibiotics to animal feed (exposing bacterial species to the environment). Quinolones have been traced back to a farm!
• 2) patient non-compliance
• 3) over-use of antibiotics (for example, using them to treat the flu, which is a virus-related infection)

Example of NDM-1: type of co-resistance: encodes for several different antibiotics: spread by R-factors or plasmids. They isolated it in a person who lived in Sweden, but from India. She got sick with a UTI, picked up resistant strain from hospital, went back to Sweden. ND stands for New Delhi.

The more antibiotics you use, the more resistance you breed.

Classical= single/single. But the entire class of antibiotics is affected. For instance, if something is resistant to the Beta lactams, all the beta lactams will be affected.

• Cross-resistance between 2 or more classes:
• 1) overlapping targets: There is a change in the chemistry on the bacterial cell. For example, the macrolide and lincosamides share a binding site (they bind to the same area), so if that chemistry changes where they bind, then it will affect both of these classes of drugs.
• 2) active efflux: ATP (energy) dependent pumps that pump drugs and chemicals outside of the cell. Many are non-specific, so the cell is resistant to two or more cells. These pumps aren't super common, though...you won't always find pumps in bacterial cells. But there is all kinds of specificities in the cell.

d. cycloserine

classic question for exam II: know mechanism of action, mechanism of resistance, etc.

Know these three differences:

Class I are potent inhibitors of beta lactamases. (Class II are weak...actually cause trans-inhibition...which is short-lived...they let go of the enzyme very easily.)

Class I are weak inhibitors of transpeptidase rxn. (Class II are potent, they bind to transpeptidase enzyme.).

Class I will cross-link. Class II will not cross link.

These inhibitors are not all resistant to beta lactamases!!! So some beta lactamases that will actually destroy them.

Why do some antibiotics have high specificity and not in other cases. Every antibiotic has different R substituent, so different chemistry will fit differently in the enzyme. The specificity is based on affinity for binding to catalytic site. Some have high affinity for binding to a beta lactamase, while others can accomodate different beta lactamases. They have different specificities because chemistry is different.

• 1) beta lactamase production
• 2) target modification (produce mutant
• 3) altering permeability (happens in gram negative bacteria...down-regulate porin channels, so antibiotic can't get to it)
• 4) active efflux (happens in phospholipid bilayer)

Gram negative harder to treat than the gram positive bacteria. Aminoglycosides can't always get into cell, so we combine with beta lactam.