Cephalosporins, Monobactams, Carbapenems Flashcards
Ceftotetan Disodium
Belongs to what subclass? Contains what group at the C-3
This drug has special affinity to? These things make it stable to many? and it is also a?
More effective than cefazolin against?
Surgical?
Chemically incompatable with what 3 drugs? what forms with one of them?
Special SEs?
Meropenem
C-4 sub? What does this prevent? No need for co admin of?
C3 side chain? Improved acitivty against?
Spectrum?
Uses?
SEs?
Monobactam
Carbapenems
Thienamycin
Structural feature:
The sulfur atom in the ring is replaced by?
Double bond where?
___ containing sidechain at?
trans carbons?
C-6 different than?
Spectrum of Thienamycin?
Resistanct to? Also an inhibitor of?
Why cant this be used?
Second Gen oral
Contains an amoxicillin like side-chain at C-7, while at C-3 there is now a 1-propenyl group conjugated with the double bond inside the six-membered ring. Both cis- and trans- forms of this side-chain are active. ____
Uses : Otitis media; Bronchitis; Pharyngitis; Skin and skin-structure infections etc. _____
Not active against MRSA, Enterobacter, Serratia, Proteus, Pseudomonas, B. fragilis ____
About 90% bioavailable following oral administration___
Other B-lactam anti
twp classes of compounds
Carbapenems and Monobactams
Structural features and Nomenclature of Cephs
What is the difference between the rings of pens vs. cephs
3rd gen parenterals
Metabolically vulnerable acetoxy group at C-3 ___
A charged pyridinium group at C-3 increases activity of the β-lactam carbonyl._____
Highly water-soluble (zwitter ionic)______
polar aminothiazole ring increases Gram - activity____
syn-Oxime ether moiety conveys β-lactamase resistance ___
Meningitis; Many serious infections (including nosocomial) , _____ + ampicillin is a combination of choice for the empiric therapy of neonatal and infant meningitis _____
Most active cephalosporin against P. aeruginosa (also better than antipseudomonal penicillins). Used in combination with an aminoglycoside in penicillin allergic patients ____
Pseudomonas UTI; Nosocomial pneumonia; Cystic fibrosis pulmonary infections; Meningitis_____
Doripenem
form?
Stable to?
Increased stability against?
among the penems most potent against?
Faropenem- Indevelopment good against anaerobes
Imipene
Analog of?
What increase chemical stability?
Spectrum:
Important!
High degree of stability against? Inhibitor of?
Not active in what form? What enzyme causes hydrolysis when used in UTIs?
Infection overview
Ceftriaxone disodium
Activity similar to?
Longest ___ among the cephalosporins due to?
A ____ dose is effective in the tx of?
Other uses?
SEs?
Clinically significant Cephs
3rd
8
- Cefotaxime
- Ceftazidime
- Ceftriaxone
- Cefixime
- Cefdinir
- Cefpodoxime proxetil
- Ceftibuten
- Cefditoren pivoxil
Clinically significant Cephs
2nd gen
4
2nd gen cephamycins 2
Cefuroxime, Cefuroxime axetil, Cefaclor, Cefprozil
Cefoxitin, Cefotetan
The newest member of the 3rd oral generation
In vivo enzymatic hydrolysis releases the active drug meaning this is?
A novel substituent at C-3
Activity is comparable to what 2 other drugs?
Indicated for?
Not indicated for children under?
Special toxicities?
3rd gen oral
Syn-oxime ether at C-7 replaced with a cis-ethylidene carboxylic acid; No side-chain at C-3 ____
Prodrug, cleaved enzymatically to release cefpodoxim (active drug), acetaldehyde, CO2, and isopropanol. An ether side-chain at C-3 ____
Oral bioavailability 75 - 90%, but decreased by food ___
Oral bioavailability of active drug ~ 50%. Absorption enhanced by food, but reduced by antacids ____
Activity similar to cefixime. Resistant to β-Lactamases ___
Better activity against S. aureus than cefixime ___
Acute otitis media; Pharyngitis; Acute bacterial exacerbations of chronic bronchitis _____
UTI; Pharyngitis; Upper and lower respiratory tract infections; Otitis media; Skin and soft tissue infections; Gonorrhea ___
4th generation ceph
Characterized by enhanced activity to? Broader fram (_) activity>
Increased stability against what type of mediated B-lactamases?
Primarily used for the empiric treatments of?
What type of agent is it?
Broad spectrum against? Including?
Due to ___ it has good cell wall penetration
___ stable low affinity for?
Not active against?
Uses?
Metabolic Deactivations Via? At what carbon position and what enzymes? What is formed once deactivated?
Double bond isomerization leads to? These have similar conformations but?
Which carbon ester tends to form double isomers?
Ertrapenem
Form?
Longest ___ among the carbapenems
Spectrum similar to meropenem but doesnt cover?
Stable to?
First gen parenteral Cephs
The first ceph drug?
Spectrum is similar to?
Stable to? And is a substitute for methicillin and dicloxacillin
Metabolic Hydrolysis at what carbon?
May enhance ____ toxicity of AGs
What type of injection is painful? Which one is preferred?
Cephalosporins
What family of antibiotic? All of the drugs in this class are of what origin?
Exhibited resistance to? But are what compared to Pen-G?
Modifications at what position leads to more active compounds?
MOA similar to?
Rarelt drug of?
Broader or comparable intrinsic activity to?
Often ____ than the comparing penicillins?
More resistant to? How does resistance go from generations?
Cidal or Static for what types of bacteria?
SEs and Allergies compared to pens.
Shouldnt be used with what patients?
3rd gen oral
Modified syn-oxime ether at C-7; Vinyl group at C-3. Oral bioavailability 40 - 50% ____
Complexes with iron. Food rich in iron / iron supplements reduces absorption (reddish stools possible!) _____
Resistant to many β-lactamases of Gram- bacteria (better than second generation drugs) ___
Fatty foods and antacids diminishes blood level. ____
Poor activity against Staph. aureus ___
• Acute exacerbation of chronic bronchitis • Sinusitis, pharyngitis, tonsillitis, otitis media • Uncomplicated skin and skin structure infections ___
Otitis media; Pharyngitis or Tnsillitis; Bronchitis Uncomplicated UTI; Uncomplicated gonorrhea ____
20 - 25% Absorbed on oral administration. ____
An unsubstituted syn-oxime at C-7 side chain; Vinyl group at C-3 ____
B-lactam
Clincally useful spectra
Aztreonam Disodium
Synewrgistic with?
uses?
affinity for>
Cefoxitin Na
Belons to what sub class?
Characterized by what substituent at the C-7?
Increased ____ increased stability against?
What group increases metabolic stability?
Increased actiivty to many ___ in the GI tract
Uses?
First Generation Cephs
Spectrum wise are similar to? But they are more stable to?
Good activity against? Modest activity against?
Good Alternative to ____ pens? But they arent good for what type of infection?
Most commonly used drug for surgerical?
Spectrum of activity? 7 things to know, what is it not active against?
First gen ceph examples
Parenteral agents 2
Oral agents? 2
Cefuroxime
Contains a ____ ether in what carbon position? This increases the stability towards? What is the reason for this? What type of ether is not effective?
What type of group at C-3 causes?
Antibacterial activitu similar to? With additional acitivty to ampicillin resistant?
Penetrates the? This makes it effective for the treatment of? But it isnt the?
3rd generation
Frame shift towards anti gram (_) away from?
Less active against? But are much more active against gram (_) than either 1/2 gen
Spectrum now includes?
Enhanced ____ stability?
Longer ___. Good what penetrations? Drug of Choice for?
Disadvantages?
Parenteral 3
Oral? 5
Cephalosporin SAR?
What is essential?
C-4 ___ required for?
Modifications at ___ and ___ cause changes in what things?
First gen oral
2
Cephalexin or Cefadroxil
Amoxicillin like side chain ____
Non-activating C-3 subsituent making it less potent but is more metabolically stable ____
Very popular drug ___
Rapidly and completely absorbed in the GI tract ____
Long T1/2 prolonged duration of action, related to slow urinary excretion qDay dosing ___
Useful against gram (-) UTI, Gram (+) infections of soft tissue, pharyngitis, minor wounds ___
Antibacterial actiivty similar to cephalexin ___
Reason for NMTT Mediated SEs?
Degradation Rxns of Cephs
What can be used in combination with Imipenem to make it safer?
What are its uses?
SEs?
Ceftolozane/ Tazobactam
Only available in what combination?
Broad spectrum against? Highly potent activity against?
Lacks activity against?
Highly stable against? Including?
What forms?
Indicated for tx of patients of what age what is this due to?
Clinically significant Cephs
4th
and MRSA Cephs
- Cefepime
- Ceftaroline, Ceftalozone (Combo with Tazo)
2nd Gen cephs
Spectrum of activity
Retained activity of ___ gen cephs with increased activity against?
H. ______, N. _____
____- positive proteus like?
Stool bacteria? Low?
Some strains of?
Increased ____ stability in comparison to ____ gen?
Not useful in what type of infections?
Parenteral 4
Oral 3
First generation Parenteral cephs
Cefazolin
Acetyl side chain at C-3 replaced by? What is the importance of this change?
Drug of Choice for? 3
Broader gram (_) activity than?
Higher ___ and longer ____
Good penetration where?
what forms?
Not stable to? Least stable of the?
Comparison of Potency between Pen and cephs
Clinically significant Cephs
1st gen
3
Cefazolin, Cephalexin, Cefadroxil
Classification, Resistance, Mechanism and Other general features of cephs
How many generations? These are based on?
Similar to Penicillins, resistance to cephs is usually due to what of 3 things?
Cephalosporins are secreted primarily through the?
Dose adjustments should be made in what pts?
Fifth gen ceph
What gives these activity with MRSA?
Broad spectrum activity against including?
Not active against?
In vivo hydrolysis generates?
Approved for the treatment of?
Most common adverse Rxns?
What is another 5th gen?
Second gen oral
Ampicillin-like side C-7 side chain. Additionally, a chlorine (Cl) substituent at C-3 position. Increased acid stability. 95% of oral dose absorbed. Stable to metabolism ______
Prodrug of Cefuroxime. A more lipophilic drug. The prodrug moiety is cleaved metabolically and the free drug is absorbed in the blood stream._____
Particularly often used against acute otitis media, also upper and lower respiratory tract, Skin, UTI ____
Enhanced activity against H. Influenza (however, not active against ampicillin resistant H. influenza) _____
Enhanced absorption of this oral drug, when adminis- tered with food ! The tablets can be dispersed in apple juice without loss of activity. ____
Well tolerated drug. Few side effects: GI (2.6%), rashes (1.5%), but serum-sickness-like illness in children frequent (Symptoms: rashes, arthritis, fever) ____
WHO drug resistance
Semisynthesis of Cephs
What was improved?
