B-Lactams Part 1 Flashcards
1
Q
Abx Targets
A
- Processes/proteins necessary for survival in prokaryotes but absent in eukaryotes
- EX: ribosomes 50s/30s, cell wall, requires folate synthesis, differences in DNA gyrase/topoisomerase
2
Q
B-Lactams
A
- Focus on cell wall synthesis
- Covalently bind to PBP active site to block enzymatic activity and prevent cell wall synthesis
- Leads to increased osmotic pressure and cell lysis/death
- EX: penicillins, cephalosporins, carbapenems, monobactams
3
Q
Bacterial Cell Wall
A
- Made up of peptidoglycans
- Glycan units joined to each other by peptide cross-links
- Cross linking is catalyzed by transpeptidases (AKA penicillin binding proteins)
4
Q
Natural B Lactam Resistance
A
- No peptidoglycan wall (atypicals)
- Impermeable to drugs (P. aeruginosa which lacks high-permeability porins)
5
Q
Acquired B Lactam Resistance
A
- Acquisition of genes that encodes resistance to multiple agents
1. B-lactamases: hydrolyze a bond in B-lactam ring which is formed or acquired from plasmids. Major cause of resistance to penicillins
2. Altered PBP: decreased binding to penicillins (mecA gene of MRSA)
3. Decreased permeability: outer cell membrane (porin) or presence of efflux pump decreasing drug perfusion
6
Q
B-Lactams are generally…
A
- Bactericidal
- Most active against growing organisms (active cell wall synthesis)
- PKPD Efficacy: T>MIC
- Many have Gram “+” and “-“ activity (not all)
7
Q
B-Lactams differ in…
A
- Spectrum of action
- PK
- Stability
- Mode of administration
- Resistance profiles
8
Q
B-Lactam Ring Classes
A
- Penicllins: thiazolidine ring
- Cephalosporins: dihydrothiazine ring
- Monobactam: no ring
- Carbapenem: unsaturated ring with sulfur external to ring
Causes differences in oral availability, stability, spectrum, half-life, etc.
9
Q
Five Classes of Penicillins
A
- Natural penicillins
- Aminopenicillins
- Anti-staphylococcal penicillins
- Carboxypenicillins (not in U.S.)
- Ureidopenicillins
Differ in stability and spectrum
10
Q
Natural Penicillins
A
- Penicillin G (parenteral) and V (oral)
- Limited spectrum, mainly Gram “+”
- Used for S. pyogenes, V. streptococci, penecillin-susceptible strains of S. pneumoniae and Enterococci, T. pallidum (syphilis), and N. meningitis
11
Q
Aminopenicillins
A
- Ampicillin, amoxicillin
- Broad spectrum, some enteric Gram “-“
- ”+” beta-lactamase inhibitors, use in conjunction to extend their coverage to B-lactamase producers like MSSA, B. fragilis, and some Gram “-“ bacterium
- Increased stability and permeability of Gram “-“ membrane
12
Q
Anti-staphylcoccal Penicillins
A
- Nafcillin, methicillin, oxacillin, dicloxacillin
- Limited spectrum, mainly Gram “+”
- Resistant to staphylococcal B-lactamases
- Used for MSSA (nafcillin, dicloxacillin) and penicillin-susceptible strains of strept
13
Q
Ureidopenicillins
A
- Piperacillin
- Works against P. aeruginosa
- Used with Zosyn almost always, some Gram “+” and “-“ activity
- Anti-pseudomonal PCNs
- Ampicillin with amino side chain converted to include Urea
- Accumulates in renal failure and may increase bleed times
14
Q
Ampicillin
A
- IV or PO
- Take on empty stomach to increase absorption
- Temperature dependent stability
- Probenecid used to slow excretion by kidney
15
Q
Amoxicillin
A
- PO
- Better absorbed
- Extremely common in use
