Pharm- Antibiotics Cell Wall

Front 1

Three stages of cell wall synthesis.

Back 1

Intracellular, cytoplasmic membrane, extracellular. All stages are potential targets.

Front 2

Describe 2nd stage of synthesis.

Back 2

Disaccharide precursor attached to phospholipid carrier. Then attached to an acceptor. Transglycosidase cuts peptidoglycan strand and inserts the disaccharide.

Front 3

Describe 3rd stage of wall synthesis.

Back 3

Cross-linking. Lysing by transpeptidase of di-alanine on end of saccharide and forms bond with glycine on the other saccharide.

Front 4

What stage to B-lactam antis attack?

Back 4

Stage three.

Front 5

What do B-lactams attach to kill the bacteria.

Back 5

penicillin binding proteins. Most important are the transpeptidases. They bind because the B-lactams mimic the d-ala-d-ala.

Front 6

What does B-lactamase do.

Back 6

Major mechanism of resistance to B-lactams. They hydrolyze it and open it up to a carboxylic acid. In Gm- bacteria they flood the periplasmic space with b-lactamase to protect themselves. Gm+ just surrounds itself.

Front 7

What mechanism of resistance led to MRSA and S. pneumonia resistance.

Back 7

Altered PBPs. B-lactams don't bind to the PBP.

Front 8

Altered membrane proteins can also give resistance. Flip for more info.

Back 8

They can alter channel sizes and other transports that still allow for essentials to pass through but severely alter ability for B-lactams to get into cell.

Front 9

What are ways to increase the residence time of penicillin G.

Back 9

Block urinary secretion with probenacid. Repository formulations with procaine penicillin G and benzathine penicillin G. These drugs are very oily and they sit there at injection site and are slowly taken up. You get long release but lower concentrations.

Front 10

Penicillin G (the model) has what deficiencies.

Back 10

Low oral bioavailability. B-lactamase inactivation. Narrow spectrum. Gm+ and Gm- cocci, spirochetes, and aerobes.

Front 11

What was the main difference between V and G taken orally.

Back 11

V taken orally is more stable at acid pH and has better bioavailability.

Front 12

Name the penicillinase resistant penicillins that were some of the first synthesized antibiotics.

Back 12

Oxacillin, nafcillin (bile excretion good in kidney failure), dicloxacillin, cloxacillin, methicillin (not used clinically). Only used for staph infections. They added bulky side groups that decreased B-lactamase affinity but not for transpeptidase.

Front 13

Why does MRSA exist biochemically? Is there any difference between nosocomial and community-acquired.

Back 13

It has altered PBPs.Community acquired doesn't have plasmid to have resistance to lots of different classes and is only resistant to B-lactams.

Front 14

Aminopenicillins (Ampicillin and Amoxicillin)

Back 14

Activity against Gm+ and limited number of Gm-. Neither stable to penicillinases. Amox is better absorbed after P.O. and is only available form.

Front 15

Antipseudomonal penicillins (Ticarcillin, piperacillin, carbenacillin)

Back 15

Enhanced activity against pseudomonas, entero, indole proteus, klebsiella. Not used for Gm+. B-lactamase sensitive. Piper is most potent. Combine with aminoglycosides for serious pseudo infection.

Front 16

Clavulanic acid, sulbactam, tazobactam

Back 16

B-lactamase inhibitors. Given synergistically.

Front 17

Cephalosporins MOA.

Back 17

Same as penicillin. More stable to B-lactamases. Generation dependent bacterial spectrum. More activity against Gm-. In the CNS use 3rd generation of higher.

Front 18

First gen cephs.

Back 18

Cefazolin and Cephalexin

Front 19

Second gen cephs

Back 19

Cefaclor, cefuroxxime, cefotetan (a cephamycin) More effective against gm- because of b-lactamase stability.

Front 20

3rd gen cephs

Back 20

Ceftazidime, ceftriaxone, cefotaxime

Front 21

4th gen ceph

Back 21

Cefepime. Mainly used for nosocomial gm- infections. B-lactamase stability. Common theme.

Front 22

5th gen ceph

Back 22

Ceftaroline. Activity against MRSA and penicillin resistant S. pneumonia. Only B-lactam active against MRSA!!!

Front 23

Carbapenems (imipenem plus cilistatin, meropenem, ertapenem)

Back 23

Cilistatin prevents degradation by human dehydropeptidase. Good agasint many resistant organisms. Carbapenemase kills the antibiotic and resistance is spreading.

Front 24

Monobactams

Back 24

Aerobic Gm- only. Resistant to B-lactamases.

Front 25

What is the major and minor hapten in anaphylaxis and how do they come about?

Back 25

Penicillin G forms an amide bond with a lysine on a protein and get a larger molecule which we then form antibodies to.

Front 26

What are some allergic symptoms to penicillin.

Back 26

Nephritis, pancytopenias, platelet aggregation impairment, electrolyte disturbances, seizures, GI upset.

Front 27

What are some adverse rxns to cephs.

Back 27

Hypersensitivity lower then pens, cross-allergy to pens in many, renal damage rarely, Agents with MTT (cefoperazone and cefotetan) inhibit vit K reductase which can cause bleeding and no clotting and it also inhibits aldehyde dehydrogenase. Seizures as well.

Front 28

Vancomycin

Back 28

Glycopeptide inhibitor of cell wall synthethis. Inhibits transglycosylation in Stage 2 of cell wall synthethis. BInds d-ala-d-ala. Don't get incorporation of disaccharide. Also recognizes after linking and can block transpeptidase action. Only works on Gm+. Enterococci has developed resistance. Staph insensitivity ad resistance can happen after long time exposure. I.V. administration but oral can be used in C. dif.

Front 29

Vanco adverse rxn

Back 29

Red Man (redneck) Syndrome. Too quick of an infusion intravenously. Ototoxicity and nephrotoxicity possible but not known.

Front 30

Telavancin

Back 30

Like vanco in action but lipid tail added and can insert into cytoplasmic membrane and disrupts membrane potential. Only used in skin stuff so far.

Front 31

Bacitracin

Back 31

Inhibt dephosphorylation of C55. Extreme nepho toxic so only used topically.

Front 32

Cycloserine

Back 32

Inhibit alanine racemase (an enzyme) and d-ala-d-ala synthetase. Drug resistant TB use.

Front 33

Fosfomycin

Back 33

Inhibits very early stage of CWS. UTIs only.