Beta lactams

Question 1

What is the structure of PCN?

Answer 1

beta lactam ring, thiazolidine ring > these are 6-aminopenicillanic acid which is conserved across PCNs, and then an R group tied to an N via amidase

Question 2

What is the peptidoglycan cell wall transpeptidase rxn?

Answer 2

Meso-DPA/gly gram - and lys/gly gram + 5 aa tail ends in a d-alanine, d-alanine which the transpeptidase cleaves the terminal alanin and puts it on the glysine of the other peptidoglycan

Question 3

Beta lactams method of action

Answer 3

beta lactams look like (are structural analogs) of the d-alanine d-alanine substrate so they bind the transpeptidase /PBP instead of it acting on the peptidoglycans; this inhibits cell wall synthesis and kills the bacteria by activating autolytic enzymes

Question 4

PCN preparation

Answer 4

prepared with a salt like Na/Cl, but the salt you prepare it with can effect the absorption time of the drug

Question 5

Resistance to beta lactams

Answer 5

1.) beta lactamases that cleaves the beta lactam bond so its doesn’t bind PBP anymore 2.) change in PBP so it doesn’t bind the antibiotics 3.) Penetrance: enter gram - via pore so change in porin or downregulation can give b-latamases time to degrade 4.)Efflux : gram - bacteria can produce an efflux pump that transport b-lactam antibiotics back across the outer membrane

Question 6

What does R group determine?

Answer 6

1. Acid stability so ability to digest orally (absorption of most oral PCN disrupted by food because of high protein binding capacity) 2. B-lactamase sensitivity 3. antibacterial spectrum , e.g. gram + or gram -

Question 7

What formulations extend absorp of PCN?

Answer 7

benzathine and procaine

Question 8

What is PCN excretion profile?

Answer 8

90% secreted by the tubules (secretion) and rest via the glomerular Nafcillin primarily cleared via billary tract

Question 9

What are the four main b lactam families

Answer 9

1.) PCN 2.) Cephalosporin 3.) Monobactam 4.) Carbapenems

Question 10

PCN G,V intake

Answer 10

G: IV, IM; V: oral

Question 11

PCN G, V clinical use

Answer 11

Gram positive organsism, esp gram positive streps also gram negative cocci (N. meningitidis) and spirochets (T Pallidum); Penicillinase sensitive

Question 12

PCN G, V Toxicity

Answer 12

Hypersensitivity rxns, hemolytic anemia

Question 13

PCN G, V resistance

Answer 13

B-lactamase can cleaves B lactam ring

Question 14

Amoxicilin, Ampicillin mechanism

Answer 14

Same as PCN, PCNase sensitive, combine with clavulanic acid to protect again destruction by B-lactamase

AmOxicillin has a greater Oral bioavailability than Ampicillin

Question 15

Amoxicillin, Ampicillin clinical use

Answer 15

Extended spectrum PCN: H. influenza, H. pylorii, E. Coli; Listeria monocytogenes; Proteus mirabilis, Salmonella, Shigella, enterococci

HHELPSS kills enterococci

Question 16

Amoxicillin, Ampicillin Toxicity

Answer 16

Hypersensitivity rxn, rash, pseudomembranous colitis

Question 17

Dicloxacillin, nafcillin, oxacillin mechanism

Answer 17

same as PCN, narrow spectrum; PCNase resistant because large bulky ring blocks access of b-lactamase to b-lactam ring

Question 18

Clinical use pcnase resistant pcns

Answer 18

(oxacillin, methacillin, cloxacillin, nafcillin); s. aureus (use naf for staph)

Except for MRSA because staph changes PBP to PBP2a

Question 19

PCNas resistant PCN toxicity

Answer 19

hypersensitivity, intersitial nephritis

Question 20

Antispeudomonals mechanism

Answer 20

piperacillin, ticarcillin; same as PCN, extended spectrum

Question 21

Piperacilin, ticarcillin clinical use

Answer 21

pseudomonas and gram - rods, PCNase sensitive so use with b-lactam inhibitors

Question 22

PCN pseudomonal toxicity

Answer 22

hypersensitivity

Question 23

B-lactamase inhibitors

Answer 23

CAST: Clavulonic Acid, Sulbactam; Tazobactam

Question 24

Cephalosporin mechanism

Answer 24

B lactam drugs that inhibit cell wall synthesis but are less susceptible to b-lactamases

organisms NOT covered by cephalosporins = LAME: listeria, atypica (chalmydia, mycoplasma), MRSA, Enterococci

Question 25

Clinical use 1st gen cephalosporins

Answer 25

cefazolin, cephalexin,

gram + cocci,

PEcK (Proteus mirabilis , E. coli, Klebsiella pneumoniae)

Question 26

2nd gen cephalosporins

Answer 26

cefoxitin, cefalcor, cefuroxime

gram + cocci

HEN PEcKS

H. flu; Enterobacter aerogenes, Neisseria spp. Proteus, E.Coli, Klebsiella, Serratia

Question 27

3rd generation cephalosporins

Answer 27

cetriaxone, cefotaxime, ceftazidime

serious gram - infections resistant to other b lactams

Question 28

Ceftriaxone

Answer 28

strep pneumo

meningitis, gonorrhea, disseminated lyme disease

Question 29

Ceftazidime

Answer 29

(3rd gen cephalosporin) pseudomonas

Question 30

4th generation cephalosporins

Answer 30

Cefepime ; gram - organisms with increased coverage against pseudomonas and gram + organisms

Question 31

5th generation cephalosporins

Answer 31

ceftaroline- broad gram + and - coverage, MRS coverage, does not cover pseudomonas

Question 32

Cephalosporin toxicity

Answer 32

Hypersentivity rxns, autoimmune hemolytic anemia; disulfiram-like rxns; vit K deficiency; cross reactivity with PCNs; increased nephrotoxicity w/ aminoglycosides

Question 33

Carbapenems mechanisms

Answer 33

Imipenem, meropenem, ertapenem, dorpenems

Imipenem broad spectrum b-lactamase resistance carbapenem, always given with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubles

“The kills is lastin with cilastin”

Question 34

Clinical use of carbapenems

Answer 34

gram + cocci, gram - rods, and anerobes, wide spectrum but significant side effects so want to limit use to life threatening infections or after other drugs have failed; Meropenem has a lower seizure risk and is stable to dehydropeptidase I

Question 35

Carbapenem toxicity

Answer 35

GI distress, skin rash, CNS toxicity, seizure at high plasma levels

Question 36

Monobactams mechanism

Answer 36

Aztreonam

Less suceptible to B-lactamases, binds PBP3; syngergistic with aminoglycosides; no cross allergenitcity with PCN

Question 37

Monobactam clinical use

Answer 37

Gram negative rods ONLY (used for PCN allergic patients or those with renal insufficiency who can’t tolerate aminoglycocides)

Question 38

Monobactam toxcitiy

Answer 38

Usually nontoxic, occasional GI upset

Question 39

Vancomycin mechanism

Answer 39

inhibits cell wall peptidoglycan formation by hinding to d-ala d-ala portion of the cell wall precursors, bactericidal, b-lactamase resistant

Question 40

Vancomycin Clinical Use

Answer 40

gram + bugs only; staph epidermidist, sensitive enterococcus, staph aureus, clostridium

Question 41

Vancomycin toxicity

Answer 41

NOT trouble free

Nephrotoxicity, Ototoxicity, Thrombophlebitis with diffuse red flushing “red man syndrome” which can be prevented by giving antihistamines and a slow infusion rate)