Chapter 6 Notes Flashcards
(30 cards)
Cephalosporin general structure
has less ring strain and lower N basicity so less reactive than Pen
7-acylamino moiety influence PBP affinity and BL stability
BL required for acylation and inhibition of PBP (forms covalent bond with PBP)
3 substituent influence oral bioavil, half life, route of admin, ADR
2-acidic (COOH) group required for PBP binding (intrinsic activity, antibacterial activity). Directs cephs toward renal elim and salt formation.
Have higher log P
3-acetoxy methyl cephs
AKA cephalosporanic acid chemically and metabolically unstable No oral activity short half life if carbamate replaces ester, you have more stable structure and can be given orally
3-thioheterocyclic cephs
Non esters chemically unstable and metab stable not metabolized No oral activity longer half life and higher PPB has good LG b/c sulfur is in conjugation
cephs with metabolically inert 3-substituents
No rxn at 3 substituent chemically and metabolically stable orally active lower PPB food may delay abs
3-QUAT ceph
ceftazidime, cefepime, ceftaroline
no oral activity due to poor GI absorption
antipseudomonal activity b/c of QUAT
can penetrate OM of some enterobact as well such as: stenotrophomonas, burkholderia, non - E. coli
all cephs are ineffective against
enterococci, listeria, legionella
major mech of resistance against ceph
modified porins that no longer allow penetration
cephamycins are resistant to BLases produced by
B. fragilis b/c of the 7-a-methoxy group
ceph with small AKI are effective against this type of strep
PRSP
AT ring of cephs allows
for enhanced binding to the essential PBPs of many G -
cephamycins and AKI are potent inducers of
chromosomal beta lactamases (AmpC)
any bug that produces BSBL will chop up
1st gen ceph
1st gen cephs are good for these infections
staph and strep that cause
endocarditis, bacterial skin infection, and osteomyelitis
NOT effective against C. dificile
when treating B. fragilis you have 4 choices
pen + BLI
clindamycin
cephamycin
metronidazole
amphoteric drugs are cleared
renally by filtration and TS
orally active cephs have
chemically and metabolically stable 3-substituent
oral prodrug with stable R3 group have ___ abs when taken with food
increased
GFR is passive and in equilibrium with
PPB
cefaclor, ceprozil, cefpodoxime, cefuroxime have ___ half lives
short
cefamandole, cefotetan, cefmetazole have ___ half lives
short to medium
ceforanid, cefonicid have ___ half lives
medium to long b/c of acidic group = more ion-ion bonding to PPB = inc PPB = inc half life
ceftriaxone has ___ half life
long b/c inc renal elimination and inc biliary elimination. Very high PPB
Also has non-metabolized 3-substituent
pen and ceph both serve as…
haptens and acylate protein to create complete antigen. There can be cross-reactivity. So, avoid giving pen/ceph if pt is positive for type I HSR history or have positive skin-test reactivity
1st gen ceph cross react in pt with pen HSR at
five times the rate of other cephs
