Term
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cephalosporins have their beta lactam ring annealed to a 6-membered dihydrothiazine ring
their system should be less strained than the penicillins and less reactive/potent
olefinic bond at C-2,3 and the methyleneacetoxy group at C-3 compensate the decrease in activity
most cephalosporins are unstable in aqueous solution |
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Definition
| chemical properties of cephalosproins |
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Term
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Definition
| inactivation of cephalosporins through hydrolysis, esterases, basic nucleophiles, and acids |
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Term
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R group position 7: incorporated by semisynthesis, impact on spectrum, significant role in classification
R group position 3: determine chemical stability, metabolic stability, minimal impact on activity, some role in classification
functional group at position 7: nothing = cephalosporins, OCH3 group = cephamycins |
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Definition
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Term
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acid stable = doesn't contain a leaving group
metabolically stable = doesn't contain an ester
carbamate = CH2OCONH2 = acid unstable (leaving group). the amide is not recognized by esterases so are metabolically stable
3-piridium group = low absorption b/c of charge |
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Definition
| SAR of the 3 position of cephalosporins |
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Term
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Definition
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Term
first generation: relatively narrow spectrum, effective primarily against gram + cocci
second generation: variable activity against Gram +, increased activity against gram -
third generation: extended spectrum of activity against gram -, against most members of enterobacteriaceae
fourth generation: includes atypicals |
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Definition
| classification of cephalosporins |
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Term
| first generation cephalosporins |
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Definition
very active against Gram + cocci
moderate activity against community acquired Moraxella catarrhalis, E. coli, Proteus, and Klebsiella
Inactive against MRSA and Enterococcus spp.
cephazolin is the preferred one from this generation due to its superior pharmacokinetic properties
used to treat S. aureus and non-enterococcal streptococcus infections when necessary to avoid the use of penicillins. skin and soft tissue infections and streptococcal pharyngitis |
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Term
chemically related to cephalosporins
enhanced stability to certain beta lactamases.
less active against staphylococci
active against Bacteroides
the enhanced activity against gram - rods is attributed to the presence of the 7-methoxy group (OCH3)
poor binding affinity to the PBPs of Gram + |
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Definition
| properties of cephaamycins |
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Term
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has comparable activity against S. aureus, S. pneumoniae, and streptococci
it has moderate activity against H. influenzae and M. catarrhalis
synthetic antibacterial
more chemically stable
the Cl at position 3 makes it stable in acidic solution (not a leaving group) |
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Definition
| characteristics of the carbacephem, Loracarbef |
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Term
more active than first and second generation
introduced to overcome the shortcomings of the earlier cephalosporins
active against facultative gram - bacilli (E. coli, Klebsiella, Proteus)
Ceftazidime is stable to the hydrolytic activity of most beta lactamases, but resistance is emerging during therapy, particularly among Pseudomonas and Enterobacter spp.
extended spectrum beta lactamases |
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Definition
| characteristics of 3rd generation cephalosporins |
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Term
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potencies against Enterobacteriaceae is higher than prior generations
effective against beta lactamase overproducing gram - strains resistant to other expanded spectrum cephalosporins
characterized by a quaternary ammonium at C-3
permeability increased through porin channels |
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Definition
| characteristics of fourth generation cephalosporins |
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Term
cephalosporins are believed to act in a similar way to penicillins
cephaclosporins are bactericidal |
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Definition
| pharmacology of cephalosporins |
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Term
several cephalosporins absorb well enough from the GI tract to permit oral administration
absorption is lower when there is food in the stomach
cephalosporins with an acetyl group at C-3 are deacetylated by liver esterases
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both the unaltered drug and the deacetylated derivatives are eliminated in the urine
most of the cephalosporins are excreted in their unchanged form by active transport in the kidney
coadministration with probenacid increases their peak serum levels and half lives |
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Definition
| absorption, metabolism, and excretion of cephalosporins |
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Term
cephalosporins penetrate well into most fluid spaces
therapeutic concentrations of cephalosporins are achieved in the peural, pericardial, and peritoneal fluids and they are transferred to the placenta
several cephalosporins have to shown to achieve appropriate therapeutic concentrations in synovial fluid and bone. 1st and 2nd generation cephalosporins do not pass well into cerebro-spinal fluid (even with inflammation)
some cephalosporins are distributed into the unobstructed biliary tract in concentrations that are effective against gram -, enteric bacteria commonly encountered as biliary tract pathogens |
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Definition
| distribution of cephalosporins |
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Term
compared to most of the antibiotics, the cephalosporins cause few significant side effects
local reactions at the site of administration are the most frequent
IM administration may be painful
IV administration may cause thrombophlebitis
intrathecal administration is hazardous and may cause convulsion
hypersensitivity is the most important systemic side effect
some cross-reactivity exists between the penicillins and cephalosporins
cephalosporins can cause 2 types of nephropathy
hematological abnormalities can also occur after cephalosporin administration |
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Definition
| adverse effects of cephalosporins |
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