8.1 PCN Flashcards
In general, how do B-lactam’s function?
Target’s PBP- binds there instead, causes NAG/NAM to fall apart –> breaks cell wall
What are the subclasses of B-lactam?
Penicillins
Cepharlosporins
Carbapenems
Monobactam
How do bugs become resistant?
6 Ps
Penetration – PCN poorly penetrate into intracellular
Bacteria hide in this compartment (i.e. Rickettsia and Legionella)
Porins – “sieving” system prevent PCN to get into periplasmic space
Some G(-) – E. Coli, Proteus M, Salmonella, and Shigella
Pumps – Efflux pump – prevent accumulation
Pseudomonas aeruginosa
Penicillinases (beta-lactamase) – G+ and G-
PBPs – mutated – not binding to penicillins
Peptidoglycan – Do not make peptidoglycan PCN ineffective (i.e. Mycoplasma, and Chlamydia)
What are the natural PCN meds on the market? Route?
PCN-G IV
PCN-V PO
What is the mechanism of anti-staph penicillins?
Bulky side chain prevent binding to beta-lactamases
What are examples of anti-staph PCNs?
Nafcillin, Oxacillin, and Dicloxacillin
Methicillin- no longer available
What bugs do anti-staph penicillins treat?
S. aureus, S. epidermidis
BUT NOT MRSA/MRSE
Are anti-staph penicillins useful for streptococci or enterococci?
No
What is the mechanism of aminopenicillins?
Amino group-> increase hydophilicity
Interferes with NAG/NAM
What bugs are targets of aminopenicillins?
E coli
P mirablis
Shigella
How does resistance to aminopenicillins form?
Drug is susceptible to beta-lactamse
Bugs with this modification defeat med
What are 2 examples of aminopenicillins?
Amoxicillin, ampicillin
What is the mechanism of aminopenicillins and b-lactamase inhibitors?
Inhibitors mimic penicillin –> bind to beta-lactamases –> enzyme inactivation
Then interferes with NAG/NAM
What are examples of aminopenicillins and b-lactamase inhibitors?
Ampicillin + Sulbactam (Unasyn) – IV
Amoxicillin + Clavulanate (Augmentin) – PO
What is the mechanism of extended-spectrum PCN?
Polar side chain allows greater penetration into G- bacteria
More resistant to G- beta-lactamases than aminopenicillins
What coverage do you get wth extended-spectrum PCN?
More active against G- bacilli including Pseudomonas
Have modest activity against anaerobes
Still susceptible to beta-lactamases of staph
What is the fullest potential of PCN?
Extended spectrum penicillin + beta-lactamase inhibitors
What are examples of extended-spectrum PCN?
Piperacillin + tazobactam (Zosyn)- broader
Ticarcillin + clavunate (Timentin)
What is the coverage of extended-spectrum PCN (e.g. zosyn)
Cover staph, aerobic G-, almost all anaerobic (except C. diff.)
What are the toxicities of PCN?
N/V/D Drug fever, rash Hepatotoxicity Neurologic toxicity Urticaria Angioedema
What is the coverage of antistaph PCN?
cover G+, but no G- activity
What is the coverage of natural PCN?
Bugs?
G+ plus few G- activity (i.e. N. meningitidis, H. influenza)
What is the coverage of Amino PCN? Bugs?
G+ plus H. influenza, E. Coli, N. meningitidis, P. mirabilis, S. enterica, Shigella…
What is the coverage of ES-PCN? Bugs?
G+ plus H. influenza, E. Coli, N. meningitidis, P. mirabilis, S. enterica, Shigella, AND PSEUDOMONAS
What is the coverage of ES-PCN w/ b-lactamase inhibitor? Bugs?
Broadest, cover most enteric G- bacilli
PSUDOMONAS
