Cell Wall Synthesis Inhibitors II Flashcards
(40 cards)
1
Q
When were cephalosporins isolated
A
1948
semi-synthetic abx (synthetic side chain)
2
Q
What do cephalosporins look like
A
- all have same cephem nucleus (B-lactam ring fused with dihydrothiazine ring)
Differ in R1 and R2 side chains - R3 = H = cephalosporin
- R4 = OMe = cephamycins
3
Q
Characteristics of cephalosporins
A
- MORE stable than penicillins (less strain on 4 membered ring)
- good PO drug
- resistant to many penicillinases/B-lactamases
- too bulky to fit into active site so can’t be inactivated
4
Q
MOA cephalosporins
A
- Identical to penicillin
- Inhibits enzymes so cell wall cannot grow
5
Q
What is the cephem core
A
B-lactam ring fused to 6-membered ring (called a dihydrothiazine ring)
6
Q
Mechanisms of resistance to cephalosporins
A
Similar to penicillins
- inactivation through hydrolysis by B-lactamases (cephalosporinases)
- Decreases access to the target (decreased entry or active efflux)
- alteration of the target transpeptidase through mutations
7
Q
Know these 3 drugs
A
Cephalexin = keflex (PO, 1st generation)
Cefdinir = omnicef (PO, 3rd generation)
Cefuroxime axetil = ceftin (PO, prodrug, 2nd generation)
8
Q
How are cephalosporins classified
A
by generation based on antimicrobial activity
9
Q
1st generation cephalosporins
A
- good against Gram +
- Modest against Gram -
- Enterococci, MRSA, and Bacteroides fragilis are resistant
10
Q
2nd generation cephalosporins
A
- somewhat better against Gram -
- active against Bacteroides fragilis
- more resistance to B-lactamases
11
Q
3rd generation cephalosporins
A
- Less active than 1st gen against Gram +
- more active against Enterobacteriaceae (Gram -), including B-lactamase producers
- subset active against Pseudomonas aeruginosa (Gram -)
12
Q
4th generation cephalosporins
A
- extended spectrum relative to 3rd gen
- increased stability to plasmid and chromosome-encoded B-lacamases
- good for empirical tx when Gram +, Enterobacteriaceae, and Pseudomonas possible
13
Q
PK of cephalosporins
A
- Cephalexin: PO, Renal excretion
- Cefuroxime: PO, Prodrug metabolized by hydrolysis, Renal excretion
- Cefdinir: PO, renal excretion
14
Q
Which cephalosporin generations have good CSF penetration
A
3rd and 4th; can treat bacterial meningitis
15
Q
Cefazolin
A
- 1st generation cephalosporin
- sometimes preferred over other 1st gen due to long half-life and good tissue penetration (NOT CNS)
- IM or IV
16
Q
Cephalexin (Keflex)
A
- 1st generation cephalosporin
- UTI and staphylococcal and strep infections
- Less active against penicillinase-producing staph
- Can be given orally, so frequently used
- similar structure to penicillin
17
Q
Cefuroxime axetil (Ceftin)
A
- 2nd generation cephalosporin
- actually a cephamycin (has methoxy group instead of hydrogen)
- less active against Gram +
- bulky, so resistant to some B-lactamases
- PRODRUG of Cefuroxime
- PO (cefuroxime given IV)
18
Q
Cefaclor
A
- 2nd generation cephalosporin
- PO
- active against haemophilus influenzae and moraxella catarrhalis
19
Q
Cefdinir (Omnicef)
A
- 3rd generation cephalosporin
- Active against Gram - and gram +, including those expressing some B-lactamases
- PO
- Bulky, so resistant
- pneumonia, bronchitis, ear infections
20
Q
Cefotaxime
A
- 3rd generation cephalosporin
- highly resistant to B-lactamases
- Good CSF penetration
21
Q
Adverse reactions to cephalosporins
A
- peptide-like so hypersensitivity –> most common and severe
- may be cross-reactivity btwn penicillin and cephalosporin hypersensitivity
22
Q
What are carbapenems
A
- synthetic B-lactam abx
23
Q
What do carbapenems consist of
A
- B-lactam ring fused to dihydropyrrole ring
- NO sulfur like in penicillin, replaced by Carbon
- core is penem (double bond on 5-membered ring)
24
Q
Carbapenems currently used in the US
A
- imipenem
- ertapenem
- meropenem
- doripenem
- ALL GIVEN IV
25
What was the first carbapenem
Imipenem; developed in 1980's
26
Imipenem
- WIDE spectrum against: Gram +/-, anaerobes
- resistant to most B-lactamases, but NOT metallo-B-lactamases
- renal metabolism via dehydropeptidases
- administered with cilastatin
27
What is cilastatin
dehydropeptidase inhibitor
| - prevents metabolism of Imipenem
28
Imipenem MOA
same as penicillin and cephalosporin
29
only carbapenem approved for menigitis
Meropenem
30
PK of Carbapenems
- penetrate all body tissues well, including CSF
- excreted renally
- given IV
- very stable and avoids most resistance
- used in complicated cases or intrabdominal infections
31
Adverse effects of carbapenems
- N/V, diarrhea, rashes, and infusion site rxn
- pt with penicillin allergy may have carbapenem allergy
- high levels with renal failure and coadministration with foscarnet = seizures
32
Indications for carbapenems
- for infections that are resistant to other abx
- for mixed aerobic/anaerobic infections
- Enterobacter infections b/c resistant to Enterobacter B-lactamase
- infections with Gram - and extended spectrum B-lactamases (ESBL)
33
Resistance to Carbapenems
- Mainly due to hydrolysis by B-lactamases (carbapenemases)
- specifically Metallo-B-Lactamases and some serine-B-Lactamases
- carbapenems still rare, so best bet if resistance to other drugs
34
Monocyclic B-Lactams: Monobactams
- sulfonate group attached to N
- limited to Gram - rods, including pseudomonas
- side chain identical to R1 of ceftazidime
- Stable against B-lactamases and metallo-
- GOOD CSF penetration
- IV
35
Aztreonam
- only Monobactam available in US
- IV
- Good CSF penetration
- CAN be given to pts with penicillin allgergies
36
Vancomycin
- glycopeptide (mostly peptide with some sugar)
- Not absorbed well = IV
- active against Gram +, esp staph (can be given for MRSA)
- quite stable b/c very bulky
37
Vancomycin MOA
- binds tightly to terminal D-Ala-D-Ala of peptidoglycan, inhibiting cross-linking
- does not inhibit the transpeptidase enzyme like B-lactams, but inhibits binding to substrate
38
Vancomycin resistance
- due to replacement of terminal D-Ala-D-Ala with D-lactate
| - Vanco can't bind and transpeptidase can cross-link
39
What is Vancomycin used for
- sepsis
- endocarditis
- MRSA
40
Vancomycin adverse rxns
- phlebitis at injection site
- chills and fever
- "red neck" syndrome due to histamine release
